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Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

DOI： 10.3390/medicina58070850

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AIM: Amid the global aging, an establishment of healthcare policies for the aged population is a common issue to be addressed. However, few studies on centenarians have reported place and cause of death (PoD and CoD, respectively) as indicators of end-of-life care quality. This study aimed to analyze trends in PoD and CoD among centenarians in Japan. METHODS: Data from death certificates from Japanese vital statistics were analyzed; 205 513 deaths occurred among centenarians (aged ≥100 years) in Japan during the period from 2006 to 2016. PoD prevalence was calculated for each CoD. Trends in PoD prevalence were analyzed using the Joinpoint regression model. Changing points, annual percentage changes, and average annual percentage changes (AAPCs) were calculated to examine trends. RESULTS: The number of deaths more than doubled from 10 340 in 2006 to 26 427 in 2016. PoDs were composed of hospitals (52.7%), nursing homes (31.4%), own homes (13.6%) and others (2.2%). Dementia and old age increased rapidly as CoD. Proportions of hospital and home deaths decreased, with AAPCs of -2.3% (95% confidence interval [CI], -2.6 to -1.9) and -2.3% (95% CI, -3.2 to -1.4), respectively. Conversely, the proportion of deaths in nursing homes rapidly increased, with an AAPC of 6.8% (95% CI, 6.0-7.7). CONCLUSIONS: The results revealed changes in PoD among centenarians in Japan. Understanding these transitions is indispensable for health policy in aging societies. Geriatr Gerontol Int 2022; ••: ••-••.

DOI： 10.1111/ggi.14416

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Evidence regarding treatment for the acute phase of COVID-19 has been accumulating, but specific treatment for long COVID/post-COVID-19 condition has not yet been established. Treatment with herbal medicine might be one treatment option for long COVID, but there has been little research on the effectiveness of herbal medicine for long COVID. The aim of this study was to clarify the prescription patterns of Kampo medicines, which are herbal medicines that originated in China and were developed in Japan, for the treatment of general fatigue due to long COVID. A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period from Feb 2021 to Dec 2021 with a focus on symptoms accompanying general fatigue and prescriptions of Kampo medicine. Among the clinical data obtained from medical records of 195 patients, clinical data for 102 patients with general fatigue and accompanying symptoms were analyzed. The patients had various symptoms, and the most frequent symptoms accompanying general fatigue were dysosmia, dysgeusia, headache, insomnia, dyspnea, and hair loss. Prescriptions of Kampo medicine accounted for 24.1% of the total prescriptions (n = 609). The most frequently prescribed Kampo medicine was hochuekkito (71.6%) and other prescribed Kampo medicines were tokishakuyakusan, ryokeijutsukanto, juzentaihoto, hangekobokuto, kakkonto, ninjin'yoeito, goreisan, rikkunshito, and keishibukuryogan. Since the pathophysiology of general fatigue after an infectious disease is, in general, considered a qi deficiency in Kampo medicine, treatments with such compensation agents can be the major prescription as a complement for the qi. In conclusion, Kampo medicine can be one of the main pharmacological treatments for long COVID accompanying general fatigue.

DOI： 10.3390/medicina58060730

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DOI： 10.1016/j.jns.2022.120232

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Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.

DOI： 10.1507/endocrj.EJ22-0093

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After the acute phase of COVID-19, some patients have been reported to have persistent symptoms including general fatigue. We have established a COVID-19 aftercare clinic (CAC) to provide care for an increasing number of these patients. Here, we report the case of a 36-year-old man who developed post-COVID fatigue after acute infection with SARS-CoV-2. In the acute phase of COVID-19, the patient's fever resolved within four days; however, general fatigue persisted for three months, and he visited our CAC 99 days after the initial infection. Examination revealed a high Aging Male's Symptoms (AMS) score of 44 and low free testosterone (FT) level of 5.5 pg/mL, which meet the Japanese criteria of late-onset hypogonadism (LOH) syndrome. Imaging studies revealed an atrophic pituitary in addition to fatty liver and low bone mineral density. Anterior pituitary function tests showed a low follicle-stimulating hormonelevel and delayed reaction of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation, indicating the possibility of hypothalamic hypogonadism in addition to primary hypogonadism seen in patients with post-COVID-19 conditions. After the initiation of Japanese traditional medicine (Kampo medicine: hochuekkito followed by juzentaihoto), the patient's symptoms as well as his AMS score and serum FT level were noticeably improved. Furthermore, follow-up tests of GnRH stimulation revealed improvements in LH responsiveness. Although many patients have been reported to meet the criteria of ME/CFS such as our case, we emphasize the possibility of other underlying pathologies including LOH syndrome. In conclusion, LOH syndrome should be considered a cause of general fatigue in patients with post-COVID-19 conditions and herbal treatment might be effective for long COVID symptoms due to LOH (264 words).

DOI： 10.3390/medicina58040536

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To promote antimicrobial stewardship, we studied antimicrobial prescription rates for uncomplicated cystitis, a common outpatient disease requiring antibiotic treatment. This multicenter retrospective study was performed from January 1, 2018, to December 31, 2020, in Japan, targeting outpatients aged ≥ 20 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting uncomplicated cystitis (N300). The data of 1445 patients were collected and that of 902 patients were analyzed. The overall median patient age was 71 years and a proportion of those aged less than 50 years was 18.8% with a female dominance (82.6%). Antimicrobials were prescribed for 884 patients (98.0%) and a total of 623 patients (69.1%) were treated with broad-spectrum drugs, including fluoroquinolones (36.0%), third-generation cephalosporins (29.9%) and faropenem (3.1%). A logistic regression model revealed that the broad-spectrum agents were significantly prescribed for the older patients, male patients, and those who visited internists. Recurrence was observed in 37 (4.1%) cases, and the multivariate analysis suggested any of age, sex, or antimicrobial types were not associated with the recurrence. Collectively, approximately two-thirds of antimicrobials prescribed for uncomplicated cystitis were broad-spectrum agents. The present data would be an indicator for antimicrobial prescriptions in uncomplicated cystitis in Japan.

DOI： 10.1038/s41598-022-09946-8

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that "general fatigue" mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients' backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT < 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = -0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID.

DOI： 10.3390/jcm11071955

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Language：Japanese   Publisher：(一社)日本感染症学会  

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BACKGROUND: Various symptoms persist even after the acute symptoms in about one third of patients with COVID-19. In February 2021, we established an outpatient clinic in a university hospital for patients with long COVID and started medical treatment for sequelae that persisted one month or more after infection. METHODS: To determine the key factors that affect the onset and clinical course of sequelae, a retrospective analysis was performed at Okayama University Hospital (Japan) between February and July 2021. We focused on changes in the numbers of symptoms and the background of the patients during a three-month period from the first outpatient visit. We also examined the relationship with SARS-CoV-2 antibody titers. RESULTS: Information was obtained from medical records for 65 patients. The symptoms of sequelae were diverse, with more than 20 types. The most frequent symptoms were general malaise, dysosmia, dysgeusia, sleeplessness, and headache. These symptoms improved in about 60% of the patients after 3 months. Patients who required hospitalization and had a poor condition in the acute phase and patients who received oxygen/dexamethasone therapy had higher antibody titers at the time of consultation. Patients with antibody titers ≥200 U/mL showed significantly fewer improvements in long COVID symptoms in 1 month, but they showed improvements at 3 months after the first visit. CONCLUSION: Long COVID symptoms were improved at 3 months after the initial visit in more than half of the patients. Serum antibody titers were higher in patients who experienced a severe acute phase, but the serum antibody titers did not seem to be directly related to the long-term persistence of long COVID symptoms.

DOI： 10.3390/jcm11051309

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DOI： 10.2169/internalmedicine.8950-21

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BACKGROUND: We analyzed data from COVID-19 patients in Japan to assess the utility of the 4C mortality score as compared with conventional scorings. METHODS: In this multicenter study, COVID-19 patients hospitalized between March 2020 and June 2021, over 16 years old, were recruited. The superiority for correctly predicting mortality and severity by applying the receiver operating characteristic (ROC) curve was compared. A Cox regression model was used to compare the length of hospitalization for each risk group of 4C mortality score. RESULTS: Among 206 patients, 21 patients died. The area under the curve (AUC) (95% confidential interval (CI)) of the ROC curve for mortality and severity, respectively, of 4C mortality scores (0.84 (95% CI 0.76-0.92) and 0.85 (95% CI 0.80-0.91)) were higher than those of qSOFA (0.66 (95% CI 0.53-0.78) and 0.67 (95% CI 0.59-0.75)), SOFA (0.70 (95% CI 0.55-0.84) and 0.81 (95% CI 0.74-0.89)), A-DROP (0.78 (95% CI 0.69-0.88) and 0.81 (95% CI 0.74-0.88)), and CURB-65 (0.82 (95% CI 0.74-0.90) and 0.82 (95% CI 0.76-0.88)). For length of hospitalization among survivors, the intermediate- and high- or very high-risk groups had significantly lower hazard ratios, i.e., 0.48 (95% CI 0.30-0.76)) and 0.23 (95% CI 0.13-0.43) for discharge. CONCLUSIONS: The 4C mortality score is better for estimating mortality and severity in COVID-19 Japanese patients than other scoring systems.

DOI： 10.3390/jcm11030821

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Coronavirus disease 2019 (COVID-19) has been spreading worldwide with unprecedented rapidity. Staphylococcus aureus is reported to frequently cause bacterial complications in patients with COVID-19. We herein present two additional cases of S. aureus pneumonia involving such patients. The first case was an obese 48-year-old man without any particular underlying diseases. The second case was another patient, a 72-year-old man, with hypertension, dyslipidemia, and steatohepatitis. Both patients developed methicillin-susceptible S. aureus pneumonia in the clinical course of COVID-19, to which antibiotic therapy with cefazolin was effectively administered. Through these cases, we emphasize that S. aureus secondary infections should be well cared with a high degree of caution in a case of critically ill COVID-19 patients.

DOI： 10.7759/cureus.22486

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Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH.

DOI： 10.18926/AMO/63203

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Language：Japanese   Publisher：(一社)日本内科学会  

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DOI： 10.31662/jmaj.2021-0129

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Herein, we report a remarkable case of post-coronavirus disease 2019 (COVID-19) diffuse alopecia that gradually improved and recovered, and the hair volume returned approximately to the pre-infection level, seven months after the patient's first diagnosis of COVID-19. Approximately 20% of patients with COVID-19 develop alopecia a few months after the acute infection phase. Telogen effluvium is the major type of COVID-19 sequela secondary to physical or psychological distress. It is reversible and is expected to improve without any treatment, and it can be addressed by explaining to the patients their conditions, sharing medical information, and eliminating psychophysical stress by managing systemic complications.

DOI： 10.7759/cureus.21160

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INTRODUCTION: The emergence of the novel coronavirus disease of 2019 (COVID-19) has led to huge disruptions in the medical field and society. The significance of training and education for experts has been increasingly acknowledged in Japan, where the number of infectious disease (ID) specialists is reportedly insufficient. In this paper, we report the results of a web-based survey that was conducted to reveal the ways in which the COVID-19 pandemic has influenced medical students' awareness of ID specialists and future career choices. METHOD: This cross-sectional descriptive study was conducted in March 2021 and targeted 717 medical students belonging to Medical School of Okayama University, Japan. The questionnaire consisted of four questions meant to assess students' knowledge and future intentions of becoming ID specialists. RESULTS: We obtained 328 eligible questionnaires (response rate: 45.7%). Of 227 (69.2%) students who were aware of ID specialists, 99 (43.6%) answered that they came to know about them only after the pandemic, 12 (3.7%) answered that their interest in being an ID specialist arose during the pandemic, while 36 (11.0%) responded that they would rather not become ID specialists. At the time of the survey, 5 students (1.5%) were aiming to become ID specialists. CONCLUSION: We observed a very low rate of interest to be an ID specialist among medical students. The experience of the pandemic does not seem to have influenced Japanese medical students to choose ID as a specialty for their careers. Continuous efforts to increase the number of ID specialists are necessary in Japan as a countermeasure against the coming pandemic.

DOI： 10.1371/journal.pone.0267587

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INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, and the United States and European authorities established criteria for the release of COVID-19 patients from isolation in October 2020. However, a huge discrepancy exists between the hospital-discharge protocol for COVID-19 patients and the release of patients from in-hospital isolation. Our initially proposed criteria for in-hospital release from isolation was not adhered to by healthcare workers (HCWs) due to prevailing concerns regarding disease infectivity. Herein, we report difficulties encountered in attempting to establish a common understanding of the management of emerging infections. METHODS: We performed a Google Form-based questionnaire survey targeting HCWs from Okayama University Hospital, Japan, via e-mail on January 21-28, 2021. The anonymous investigation required respondents to provide information regarding their background as well as perceptions regarding the requirement, level of understanding, and readiness for developing release criteria. RESULTS: We obtained 150 eligible responses, including 57 (38.0%) from medical doctors and 53 (35.3%) from nurses. Most HCWs managing COVID-19 patients advocated for the implementation of the criteria, whereas those not working in that capacity did not (p<0.001). Over half of the HCWs indicated discomfort at seeing COVID-19 patients transitioning to general management even after meeting the criteria. CONCLUSIONS: It was challenging to establish a common understanding regarding the ideal criteria for in-hospital release of COVID-19 patients from isolation in our hospital. The dissemination of our experiences and multifaceted discussions with HCWs would be of great value as a countermeasure against the emergent pandemic.

DOI： 10.1371/journal.pone.0266853

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DOI： 10.1093/jac/dkab464

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DOI： 10.1093/cid/ciab1011

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Objective: To describe a case of anti-glomerular basement membrane (GBM) nephritis that occurred shortly after initiation of nebulized tobramycin (TOB) therapy using intravenous solution, suggesting an association with the inhalation therapy and the disease onset. Background: With the emergence of antimicrobial resistance, clinical importance of aminoglycosides that usually remain susceptibility against gram-negative organisms is increasingly acknowledged. Despite the growing number of evidence supporting the effectiveness of aminoglycoside inhalation therapy for respiratory tract infections, its clinical application has yet to be widely approved by Japanese health insurance. Case Presentation: A 79-year-old Japanese woman had developed amyotrophic lateral sclerosis and experienced recurrent pneumonia mainly caused by Pseudomonas aeruginosa, which required monthly treatments with broad-spectrum antibiotics. Owing to the limited approval, we had no choice but to use intravenous TOB solution for inhalation therapy as an off-label use under an endorsement of the Institutional Review Board of the hospital. Although the repeated pneumonia subsided, the patient subsequently needed immunosuppressive therapy along with plasma exchanges for the treatment of anti-GBM nephritis. Conclusion: Although this off-label use of intravenous solutions is common in both clinical and research purposes, our case raised an issue that its safety needs to be re-evaluated.

DOI： 10.1089/jamp.2021.0053

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to the modern healthcare system and led to increased burnout among healthcare workers (HCWs). We previously reported that HCWs who engaged in COVID-19 patient care had a significantly higher prevalence of burnout (50.0%) than those who did not in November 2020 (period 1). We performed follow-up surveys in HCWs in a Japanese national university hospital, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks, and the Maslach Burnout Inventory in February 2021 (period 2) and May 2021 (period 3). Periods 1 and 3 were amid the surges of COVID-19 cases, and period 2 was a post-surge period with a comparatively small number of COVID-19 patients requiring hospitalization. Response rates to the surveys were 33/130 (25.4%) in period 1, 36/130 (27.7%) in period 2, and 56/162 (34.6%) in period 3, respectively. While no consistent tendency in the prevalence of burnout based on variables was observed throughout the periods, the prevalence of burnout tends to be higher in periods 1 and 3 in those who engaged in COVID-19 patient care in the last 2 weeks (50.0%, 30.8%, 43.1% in period 1, 2, and 3, respectively). Given the prolonged pandemic causing stigmatization and hatred against HCWs leading to increased prevalence of burnout, high-level interventions and supports are warranted.

DOI： 10.3390/ijerph182111581

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Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

DOI： 10.1507/endocrj.EJ21-0488

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DOI： 10.1080/1120009X.2021.1994689

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An 89-year-old woman who had type 2 diabetes mellitus suddenly presented with abdominal pain. Abdominal computed tomography showed thickening of the wall and intramural gas in the gastric hilum, suggesting emphysematous gastritis. The patient underwent treatment with a proton-pump inhibitor and broad-spectrum antibacterial agents.

DOI： 10.1002/ccr3.5094

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

新型コロナウイルス感染症対策の一環として,「新型コロナウイルス感染症対応従事者慰労金交付事業」が実施されたが,その影響・有効性に関するデータは乏しい。2021年4月26日〜5月31日に,岡山県・香川県・広島県の医療機関に勤務する職員を対象にウェブ・アンケートによる横断調査を実施した。1001名からの回答において,慰労金受給率は95.8%であり,59.5%は本事業に満足したと回答した。職種別満足度は,医師(60.8%),メディカルスタッフ(63.9%)に比べて看護職(46.3%)で低かった(p<0.001)。医療機関内職員のみならず,救急隊員,保健所職員,高齢者介護施設の職員も慰労金が支払われるべき業種として高率に理解を得た。慰労金交付事業は,医療従事者等の外的モチベーションとして概ね機能したと考えられるが,給付金額や対象者の選定に関しては検討の余地がある。(著者抄録)

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Language：Japanese   Publisher：(株)ライフメディコム  

新型コロナウイルス感染症(COVID-19)が最初に報告されてからおよそ1年半が経過したが、いまだ収束の兆しの見えない世界的流行のなかで「Long-COVID」ないし「post-acute sequelae of COVID-19(PASC)」と定義され、一般には「コロナ後遺症」として知られる、急性期以降に残存する症状に悩まされる患者が多く存在している。そのなかでも「倦怠感」は、最も多い症状として報告され、COVID-19罹患後に4割程度の患者が自覚すると言われている。倦怠感は視認できず検査での客観的評価も難しい症状である一方で、さまざまな要因が複雑に絡みあって生じており病態メカニズムも未解明なところが多く、診療に難渋する。われわれは2021年2月にLong-COVID/PASCを専門的に診療する「コロナ・アフターケア(COVID-19 aftercare:CAC)外来」を大学病院内にいち早く設立し、倦怠感などの症状に悩む患者の診療と研究・教育に取り組んできた。本稿ではそうしたわれわれの診療経験も踏まえ、診断や治療を行ううえでの対面診療の必要性や総合診療的アプローチの重要性についても触れながら、Long-COVID/PASCにおける倦怠感について概説する。(著者抄録)

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BACKGROUND: Scientific evidence suggest that hand hygiene as one of the most effective measures to control infection. To promote good hand hygiene practices, the World Health Organization introduced May 5 as World Hand Hygiene Day (WHHD), and international stakeholders established Global Handwashing Day (GHD) on October 15. However, its contributions to raising public awareness of hand hygiene is unclear. METHODS: This study evaluates the impact of the WHHD and GHD on the public awareness of hand hygiene in Japan, the United Kingdom, the United States, and worldwide from 2016 to 2020, using the relative search volume of "Hand hygiene" in Google Trends as a surrogate. To identify a statistically significant timepoint of a trend change, we performed Joinpoint regression analysis. RESULTS: Upticks of the relative search volumes as well as joinpoints were noted worldwide around the WHHD and GHD from 2016 to 2019, but no joinpoints were identified around the WHHD and GHD in 2020. No such changes were observed in Japan, the United Kingdom, and the United States during these periods. CONCLUSIONS: While the WHHD was originally established to raise awareness of hand hygiene in healthcare facilities, our result suggests that the WHHD and GHD may not have effectively disseminated the importance of hand hygiene to the general public at a country level. Additional policy measures to advocate hand hygiene to the public are necessary to communicate its benefits.

DOI： 10.1016/j.ajic.2021.08.033

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The emergence of high-level daptomycin (DAP)-resistant (HLDR) Corynebacterium striatum has been reported as a result of loss-of-function point mutations or premature stop codon mutations in a responsible gene, pgsA2. We herein describe the novel detection of an HLDR C. striatum clinical isolate, in which IS30-insertion was corroborated to cause destruction of pgsA2 gene. We isolated an HLDR C. striatum from a critically ill patient with underlying mycosis fungoides who had been treated with DAP for 10 days. With a sequence investigation, IS30-insertion was discovered to split pgsA2 in the HLDR C. striatum strain, which may cause disrupted phospholipid phosphatidylglycerol (PG) production. Future studies should survey the prevalence of IS-mediated gene inactivation among HLDR C. striatum clinical isolates.

DOI： 10.1007/s10096-021-04369-1

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To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future.

DOI： 10.1038/s41598-021-00206-9

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DOI： 10.1093/qjmed/hcab260

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The options available for treating infections with carbapenemase-producing Enterobacteriaceae (CPE) are limited; with the increasing threat of these infections, new treatments are urgently needed. Biapenem (BIPM) is a carbapenem, and limited data confirming its in vitro killing effect against CPE are available. In this study, we examined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of BIPM for 14 IMP-1-producing Enterobacteriaceae strains isolated from the Okayama region in Japan. The MICs against almost all the isolates were lower than 0.5 µg ml-1, indicating susceptibility to BIPM, while approximately half of the isolates were confirmed to be bacteriostatic to BIPM. However, initial killing to a 99.9 % reduction was observed in seven out of eight strains in a time-kill assay. Despite the small data set, we concluded that the in vitro efficacy of BIPM suggests that the drug could be a new therapeutic option against infection with IMP-producing CPE.

DOI： 10.1099/jmm.0.001430

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OBJECTIVES: To evaluate the impact of the World Antimicrobial Awareness Week (WAAW) on public awareness of antimicrobial resistance using Google Trends analysis. METHODS: The impact of WAAW on public awareness of 'antimicrobial resistance' (AMR), 'antibacterial', and 'antibiotics' in Japan, the UK, the United States, and worldwide from 2015 to 2020 was analyzed, using the relative search volume (RSV) of Google Trends as a surrogate. A joinpoint regression analysis was performed to identify a statistically significant time point of a change in trend. RESULTS: No joinpoints around WAAW were identified in Japan, the United Kingdom, or the United States from 2015 to 2020 with RSVs of 'AMR', whereas increasing RSVs were noted worldwide in 2017 and 2020. Further, there were decreasing RSVs of 'antibiotics' in the first half of 2020, which could be due to the COVID-19 pandemic. The study results suggest that WAAW did little to improve public awareness of AMR in the selected countries despite its contribution worldwide. CONCLUSIONS: This study implies that we need to develop a more effective method to improve public awareness to fight against AMR.

DOI： 10.1016/j.ijid.2021.08.018

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Introduction The long-term clinical course, prognosis, and optimal management of symptoms and conditions after the acute phase of coronavirus disease 2019 (COVID-19) remain to be elucidated. The purpose of this study was to clarify the characteristics of patients referred to a COVID-19 aftercare (CAC) clinic established at a tertiary academic hospital in Japan. Methods This study was a descriptive case series study. All patients who visited the CAC clinic between February 15 and September 17 in 2021 were included. Patients' background, chief complaints, and clinical courses after the onset of COVID-19 were described. Results A total of 87 Japanese patients (median age, 40.0 years; interquartile range [IQR], 26.5-53.0 years; 52.9% women) were referred to the CAC clinic. The median interval between the onset of COVID-19 and the visit to the clinic was 79.0 (IQR, 52.5-112.0) days. Referral sources were hospitals (36 patients), clinics (47 patients), a local healthcare center (3 patients), and other (1 patient). The most common chief complaint was general fatigue (50.4%) followed by dysosmia (28.7%), dysgeusia (26.4%), hair loss (18.4%), headache (17.2%), dyspnea (16.1%), and dyssomnia (13.1%). Respiratory symptoms were common in the early stages of the disease but were less common as the chief complaints when visiting the clinic. On the other hand, neurological, psychiatric, and extremity symptoms were predominant one month after the onset of COVID-19. Conclusions Regardless of the severity in the acute phase, patients visiting our CAC clinic suffered from a variety of symptoms. General physicians skilled in using a comprehensive approach would be optimal to see patients with such complex symptoms.

DOI： 10.7759/cureus.18568

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(公社)日本医師会  

国際化を背景に、在日外国人も新型コロナウイルス感染症(COVID-19)に罹患しているが、本邦でその診療上の課題に関する文献はない。2020年2月からの1年間に岡山大学病院総合内科・総合診療科に入院した、外国人COVID-19患者全5人を対象として、患者背景や言語状況、入院中のトラブルや解決策について診療録から抽出した。全員が日本語の書字・読字が全く不能であり、うち1人は日常会話も困難で電話医療通訳サービスを要したが、担当医や看護師に加えて、国際診療支援センターや臨床栄養部、精神科などと連携することで隔離解除まで入院継続が可能であった。COVID-19では本人の希望に沿わない入院や予定外入院のため、通常の外国人診療に比して負担・課題が大きい。特に言語面での制約は、隔離管理下での意思疎通や同意書の取得などの面で障壁となることが明らかとなった。院内組織の連携と、病院を超えた情報共有による病軟な対応が重要である。(著者抄録)

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COVID-19 patients treated with anti-inflammatory drugs are rarely complicated by candidemia. Since immunosuppressive therapy can blunt inflammatory reactions, clinicians should actively survey latent candidemia during severe COVID-19 treatment.

DOI： 10.1002/ccr3.4858

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Objectives Vitamin D deficiency, which is common worldwide, increases the risks of falls and fractures and can lead to increased morbidity and mortality. However, the clinical utility and relevance of vitamin D activation remain unknown. The aim of the present study was to clarify the clinical usefulness of serum 1,25-dihydroxyvitamin D (1,25D)/25-hydroxyvitamin D (25D) ratio for assessment of the extent of bone metabolism. Methods We retrospectively screened data for 87 patients whose serum 1,25D and 25D levels were measured. Eight patients who were taking vitamin D preparations were excluded, and data for 79 patients (33 males and 46 females) were analyzed. Since menopausal status can be associated with serum vitamin D level, we divided the patients by gender and divided the female patients into two groups at the age of 50 years. Results The median serum 1,25D/25D ratio was significantly lower in males than in females, with the most considerable difference in all males [4.1 (interquartile range: 2.3-5.8) × 10-3] versus elderly females (aged ≧50 years) [7.9 (3.3-10.1) × 10-3). Main disorders were endocrine (30.6%), inflammatory (18.5%), and bone-related (16.7%) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual-energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between the 1,25D/25D ratio and serum levels of inorganic phosphate (iP), parathyroid hormone, and alkaline phosphatase (ALP). The 1,25D/25D ratio had gender-specific characteristics: the ratio was significantly correlated with age in males (R=-0.49), while it was significantly correlated with BMI in females (R=0.34). Conclusions The results of this study suggested that vitamin D activity is negatively correlated with bone mineral density, being reduced in aged males but enhanced in obese females.

DOI： 10.7759/cureus.18070

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DOI： 10.1007/s11739-021-02766-0

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Pregnancy was reported to be a risk factor for coronavirus disease 2019 (COVID-19), with an increased risk for premature birth. Corticosteroids and remdesivir are used for patients with COVID-19; however, there is no established treatment for these patients. In particular, the effective management of pregnant, critically ill patients with COVID-19 remains unknown. We describe a 34-year-old, critically ill woman at 30 weeks of gestation with COVID-19, who was successfully treated with remdesivir and combined high-dose betamethasone (12 mg/day for two days) and methylprednisolone (125 mg/day for three days) followed by steroid tapering. During treatment, fetal biophysical profile scores on obstetric ultrasound were normal; her pregnancy course progressed well. Since high-dose corticosteroids improve fetal lung maturation and as well as cytokine storm due to COVID-19, this case provides an insight into the management of pregnant COVID-19 patients.

DOI： 10.7759/cureus.17398

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INTRODUCTION: The global spread of emerging infections has increased the demand for infectious disease (ID) experts. There is no established method to evaluate the sufficiency of professionals on a regional basis. We aimed to determine the correlation of the number of ID doctors and certified nurses in infection control (CNIC) with the prevalence of representative antimicrobial-resistant (AMR) pathogens across the 47 prefectures in Japan using publicly available databases. METHODS: We determined the number of ID doctors and CNIC registered in each prefecture based on the Japanese Association for Infectious Diseases and the Japanese Nursing Association websites and calculated their numbers per 100,000 population. Data on representative AMR pathogens were extracted from the Japan Nosocomial Infections Surveillance database. Spearman's correlation coefficient was used to measure statistical associations. RESULTS: There was no epidemiologically applicable correlation between the deployment of ID doctors and CNIC and the isolation rates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime- or levofloxacin-resistant Escherichia coli and Klebsiella pneumoinae, and meropenem-resistant Pseudomonas aeruginosa. Solely, the isolation rate of levofloxacin-resistant K. pneumoinae and the number of CNIC were statistically correlated (correlation coefficient = -0.33; p = 0.02), while the isolation rate of cefotaxime-resistant E. coli was paradoxically correlated with the number of ID doctors (correlation coefficient = 0.33; p = 0.02). Conclusions: Our macroscopic analysis using the open database was not a reliable method to evaluate the sufficiency of ID experts across the prefectures in Japan. A scheme to assess the appropriate distribution of ID experts should be developed.

DOI： 10.7759/cureus.16918

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Primary Sjögren's syndrome (SS) is an autoimmune disease that usually affects the exocrine glands in mid-dle-aged women. Fifteen percent of SS patients experience severe systemic extraglandular complications, and pleuritis is one of the rare complications of SS. We report the case of an elderly Japanese man who initially pre-sented with a prolonged fever and chest pain and was finally diagnosed with primary SS-associated pleuritis. Of the nine reported cases of primary SS that initially presented with pleuritis, up to six cases were elderly males. This case highlights the complication of pleuritis among elderly males with primary SS.

DOI： 10.18926/AMO/62409

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DOI： 10.1016/j.clinthera.2021.07.007

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We have presented a case of barium appendicitis, which is a rare complication of barium enema studies. Barium sulfate is used widely for gastrointestinal radiographic studies and is associated with few complications. Clinicians need to be fully aware of this complication.

DOI： 10.1002/ccr3.4583

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Granulocyte colony-stimulating factor (G-CSF) is a relatively new drug that is used for recovery of chemotherapy-associated neutropenia. It is known to cause bone pain, headache and fatigue as side-effects; however, large-vessel vasculitis is extremely rare and its relation with G-CSF remains unknown. We describe a 49-year-old woman in whom arteritis developed after chemotherapy and subsequent G-CSF administration. She had experienced pinealoma 3 months ago and received surgery and chemotherapy, leading to neutropenia. After administration of lenograstim at 100 μg/day for 1 week, high fever and neck pain appeared. White blood cell count and serum levels of C-reactive protein and interleukin-6 were increased to 37,930/μL, 23.71 mg/dL, and 241 pg/mL, respectively. Contrast-enhanced computed tomography revealed thickened walls of large vessels including the bilateral common carotid artery (CCA), right brachiocephalic artery, and ascending aorta. Ultrasonography showed wall thickening of the CCA (maximum of intima media thickness: right, 2.9 mm; left, 3.2 mm). As differential diagnoses, infection, chemotherapy, autoimmune diseases, and cancer were considered other than G-CSF. Blood culture tests, lumbar puncture, β-D-glucan tests, and tests for viral antibodies indicated no active infection, and autoantibodies were negative. Empirical antibiotic therapy was ineffective. The score of Naranjo's algorithm to lenograstim was 6, indicating "probable" causality. Considering the clinical course and test results, we made a diagnosis of G-CSF-associated arteritis and commenced glucocorticoid therapy, which drastically improved the symptoms and inflammation. Clinicians should be aware of this uncommon but significant complication of GCS-F administration, for which glucocorticoid treatment can be a useful therapeutic option.

DOI： 10.1080/24725625.2020.1857022

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Objective During the ongoing global pandemic of novel coronavirus disease 2019 (COVID-19), an emerging infectious disease, the implementation and execution of infection prevention and control (IPC) is of paramount importance. In this study, we aimed to assess the current deployment of infection control medical personnel in Okayama prefecture, who are supposed to play an essential role to prevent the outbreak of infectious diseases, and the current prevalence of antimicrobial-resistant (AMR) bacteria isolated in Okayama. Materials and methods This was a descriptive study using publicly available data. The numbers of infectious disease (ID)-doctors and the certified nurses in infection control (CNIC) per 100,000 population in 47 prefectures in Japan were calculated. We then compared the detected proportions of AMR pathogens among the prefectures in 2019 to be employed as a comparative parameter, which was obtained from Japan Nosocomial Infections Surveillance (JANIS) data. Results The number of ID-doctors was the 11th highest in Japan; however, they were unevenly distributed in southern Okayama, particularly at three tertiary hospitals. While the deployment of CNIC was geographically less uneven in the prefecture, their number was lower than the domestic average. According to the JANIS data, isolation rates of AMR pathogens were high in Okayama compared to other prefectures in Japan: vancomycin-resistant Enterococcus faecium (the third-worst); cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae (the third-worst and the second-worst, respectively); and meropenem-resistant Pseudomonas aeruginosa (the worst). Conclusions Our assessment provides underlying data and reinforces the need for educating multi-professional experts in the field of infectious diseases to prevent future public health threats in Okayama.

DOI： 10.7759/cureus.16643

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The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect™ 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.

DOI： 10.1016/j.jiac.2021.05.001

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Background: Carbapenemase-producing Enterobacterales (CPE) are spreading in hospitals, environment and retail foods in Yangon, Myanmar. Objectives: To investigate whether CPE colonize healthy individuals living in Yangon and whether clinical-related strains are spreading in the community. Methods: CPE was isolated from faecal samples obtained from healthy Japanese residents of Yangon with no history of hospitalization. Isolates were subjected to WGS using short- and long-read sequencers and compared with those previously isolated in Yangon. Results: Six Escherichia coli strains harbouring blaNDM-1 or blaNDM-5 belonging to five different STs - ST10, ST38, ST48, ST410 and ST8453 - were isolated from 69 volunteers. The ST38 isolates were related to those previously isolated from retail food in Yangon. The ST410 and ST8453 isolates were highly related to previous Yangon isolates including those of clinical and food origins. Conclusions: The analysis suggested the acquisition of blaNDM-positive E. coli, which are disseminating in a clinical setting and through retail foods, by healthy residents in Yangon.

DOI： 10.1093/jac/dkab070

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Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho=0.62), soluble interleukin-2 receptor (sIL-2R; rho=0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho=-0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

DOI： 10.18926/AMO/62221

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho = 0.62), soluble interleukin-2 receptor (sIL-2R; rho = 0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho = -0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

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DOI： 10.2169/internalmedicine.5314-20

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DOI： 10.1136/postgradmedj-2020-138416

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INTRODUCTION: Adverse drug events (ADEs) are a major cause of mortality. OBJECTIVE: We examined long-term trends for ADE-related deaths in Japan. METHODS: This observational study was conducted using the Japanese Vital Statistics from 1999 to 2016. Data for all ADE-related deaths were extracted using International Classification of Diseases, Tenth Revision codes. We analysed ADE-related deaths by age and sex and calculated crude and age-standardised mortality rates (ASMR) per 100,000 people. We used Joinpoint regression analysis to identify significant changing points in mortality trends and to estimate annual percentage change (APC). RESULTS: In total, 16,417 ADE-related deaths were identified. The crude mortality rate for individuals aged ≥ 65 years was higher than that of young individuals. The ASMR per 100,000 people increased from 0.44 in 1999 to 0.64 in 2016. The crude mortality rate increased from 0.44 in 1999 to 1.01 in 2016. The APC of ASMR increased at a rate of 2.8% (95% confidence interval [CI] 1.4-4.2) throughout the study period. In addition, crude mortality increased at a rate of 5.7% (95% CI 4.2-7.3) annually from 1999 to 2016. The ADE-related mortality rate was higher for men than for women during the study period. CONCLUSIONS: The number of and trend in ADE-related deaths increased in Japan from 1999 to 2016, particularly in the older population.

DOI： 10.1007/s40264-020-01037-9

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DOI： 10.1111/ggi.14159

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BACKGROUND: We evaluated the effect of the two-dose vaccination strategy, which has been a widely adopted as childhood routine schedule worldwide to acquire herd immunity, on healthcare workers (HCWs) in Japan. METHODS: Between 2010 and 2019, antibody titers for measles and rubella were measured annually among newly employed HCWs at Osaka University Hospital, Japan, using Enzygnost® assays (Siemens Healthcare Diagnostics Co. Ltd., Marburg, Germany). The data were categorized by age to compare the antibody positivity rates and antibody titers among no-vaccine, single-dose, and two-dose groups. RESULTS: Over the 10-year period, the annual antibody positivity rates for measles and rubella were 84.0%-95.3% and 90.0%-94.5%, respectively, without any particular trend. The antibody titers for measles (median [interquartile range]: 8.4 [3.9, 20] vs. 6.1 [3.5, 12]) and rubella (11 [5.5, 20] vs. 6 [3.7, 11]) were statistically lower (p < 0.001) in the two-dose generation than in the single-dose generation. DISCUSSION: A shift from single-dose to two-dose vaccination did not yield an increase in antibody positivity rates for both measles and rubella among HCWs. Notably, antibody titers were significantly lower in the two-dose generation. CONCLUSION: Despite several limitations, our data suggests a paradoxical vulnerability in young HCWs who received the two-dose vaccination in a view of sero-positivity rates.

DOI： 10.1016/j.jiac.2021.04.006

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BACKGROUND AND AIM: The current prevalence of hepatitis C virus infection and hepatitis C virus-associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus-associated mortality in Japan. METHODS: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus-associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age-standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. RESULTS: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age-standardized mortality rate was higher in women than in men. The average annual percentage change was -3.8% (95% confidence interval: -5.0 to -2.5). The declining trend was more rapid in men (-4.5%, 95% confidence interval: -5.3 to -3.6) than in women (-2.7%, 95% confidence interval: -3.8 to -1.6). CONCLUSIONS: Trends in hepatitis C virus-associated mortality rates have declined in an accelerating manner in Japan, especially among men.

DOI： 10.1111/jgh.15517

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RATIONALE: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. PATIENT CONCERNS: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. DIAGNOSIS: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. INTERVENTIONS: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. OUTCOMES: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. LESSONS: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.

DOI： 10.1097/MD.0000000000025265

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This study examined temporal trend, seasonality, and geographical variations of legionellosis incidence and mortality in Japan. This nationwide observational study used the Japanese Vital Statistics and Infectious Diseases Weekly Report (1999-2017) data to calculate legionellosis crude and age-adjusted incidence and mortality rates per 100,000 population by age and sex. Incidence was compared among the 4 seasons and regional incidence among 47 prefectures. Of 13,613 (11,194 men) people with legionellosis in Japan, 725 (569 men) were fatal. Increasing incidence trend occurred from 0.0004 (1999) to 1.37 (2017) per 100,000 population. People aged ≥ 70 years accounted for 43.1% overall; men's age-adjusted incidence rate was consistently approximately five times higher than for women. Significantly higher incidence occurred in summer than in winter (p = 0.013). Geographically, highest incidence (≥ 2.0 per 100,000 population) occurred in Hokuriku District, with increasing trends in Hokkaido and middle-part of Japan. Estimated fatality rates decreased consistently at 5.9% (95% confidence interval: - 8.1, - 3.5) annually, from 1999 to 2017, with no trend change point. Increasing legionellosis incidence occurred in Japan during 1999-2017, with declining estimated fatality rates. In this aging society and warming world, disease clinical burden may further deteriorate in future due to increasing incidence trends.

DOI： 10.1038/s41598-021-86431-8

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The coronavirus disease 2019 (COVID-19) global pandemic has drastically changed how we live and work. Amid the prolonged pandemic, burnout of the frontline healthcare professionals has become a significant concern. We conducted a cross-sectional survey study to provide data about the relationship between the COVID-19 pandemic and the prevalence of burnout in healthcare professionals in Japan. Healthcare workers in a single Japanese national university hospital participated in the survey, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks and the Maslach Burnout Inventory. Of those, 25.4% fully answered the survey; 33.3% were doctors and 63.6% were nurses, and 36.3% engaged in care of COVID-19 patients in the past 2 weeks. Compared to those belonging to General Medicine, those in Emergency Intensive Care Unit were at higher risk of burnout (odds ratio (OR), 6.7; 95% CI, 1.1-42.1; p = 0.031). Of those who engaged in care of COVID-19 patients, 50% reported burnout while 6.1% did not (OR 8.5, 95% CI; 1.3-54.1; p = 0.014). The burnout of healthcare workers is a significant concern amid the pandemic, which needs to be addressed for sustainable healthcare delivery.

DOI： 10.3390/ijerph18052434

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The global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a major concern in public health. Due to the existence of the diversity of carbapenemases, development of an easily available, cost-effective multiplex detection assay for CPE is required worldwide. Using clinically available and reliable equipment, COBAS® z480 (Roche Diagnostics K.K., Tokyo, Japan), we developed a multiplex real-time PCR assay for the detection of two combinations of carbapenemases; first, blaNDM, blaKPC, and blaIMP (Set 1), and second, blaGES, blaOXA-48, and blaVIM (Set 2). We constructed standard curves for each carbapenemase gene using serial dilutions of DNA standards, then applied reference or clinical isolates with each carbapenemase gene to this assay. The multiplex assay showed satisfactory accuracy to detect CPE genes, with the correlation coefficients of greater than 0.99 for all genotypes. The assay appropriately differentiated the reference or clinical strains harboring each carbapenemase gene without cross reactivity. Lastly, the assay successfully detected multiple genes without false-positive reactions by applying six clinical isolates carrying both NDM and OXA-48-like carbapenemase genes. Major advantages of our assay include multiplicity, simple operation, robustness, and speed (1 h). We believe that the multiplex assay potentially contributes to early diagnosis of CPE with a diverse genetic background.

DOI： 10.3390/pathogens10030276

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BACKGROUND: The COVID-19 pandemic has negatively affected medical education. However, little data are available about medical students' distress during the pandemic. OBJECTIVE: This study aimed to provide details on how medical students have been affected by the pandemic. METHODS: A cross-sectional study was conducted. A total of 717 medical students participated in the web-based survey. The survey included questions about how the participants' mental status had changed from before to after the Japanese nationwide state of emergency (SOE). RESULTS: Out of 717 medical students, 473 (66.0%) participated in the study. In total, 29.8% (141/473) of the students reported concerns about the shift toward online education, mostly because they thought online education would be ineffective compared with in-person learning. The participants' subjective mental health status significantly worsened after the SOE was lifted (P<.001). Those who had concerns about a shift toward online education had higher odds of having generalized anxiety and being depressed (odds ratio [OR] 1.97, 95% CI 1.19-3.28) as did those who said they would request food aid (OR 1.99, 95% CI 1.16-3.44) and mental health care resources (OR 3.56, 95% CI 2.07-6.15). CONCLUSIONS: Given our findings, the sudden shift to online education might have overwhelmed medical students. Thus, we recommend that educators inform learners that online learning is not inferior to in-person learning, which could attenuate potential depression and anxiety.

DOI： 10.2196/25232

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DOI： 10.1136/bcr-2021-241640

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 +/- 1.5 years old), decreases in serum FT levels to <8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The percentages of patients with low FT levels were high in the >= 50 years age group (83%), the HbA1c <7% group (67%), and the 25 <= BMI < 30 kg/m(2) group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R= 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = -0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R= 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males.

DOI： 10.18926/AMO/61424

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The genus Tsukamurella is a fastidious, environmental organism that potentially causes various infections in humans. Due to the morphological and biochemical similarities to others pathogens, such as Gordona, Rhodococcus, Corynebacterium, Nocardia, and Mycobacterium, a molecular-based approach is indispensable to correctly identify them. Herein, we describe a case of Tsukamurella inchonensis bacteremia complicated with septic pulmonary emboli (SPE), which is the first in the literature. A 44-year-old Japanese woman diagnosed with tongue cancer had undergone partial tongue resection. While receiving chemotherapy and radiotherapy, she developed high fever. Chest computed tomography suggested multiple emboli at the bilateral, peripheral lungs, indicating SPE. Blood culture detected Gram-positive rods, to which matrix-assisted laser desorption/ionization-time of flight mass spectrometry failed to identify. Then, we attempted to characterize it by 16S rRNA sequence, which suggested the organism to be Tsukamurella species but resulted in low resonance of the species-level identification. Additionally, we employed a confidence gene targeting groEL, leading to 100% matching (753/753 bps) with T. inchonensis NCTC 10741 (GenBank accession no. LR131273.1), which has been incorrectly registered as wrong species name Tsukamurella paurometabola in the database. Under the diagnosis of T. inchonensis-associated SPE, we successfully treated the patient with imipenem/cilastatin administration for 4 weeks. Sequencing analysis of groEL was of great use in identifying the organism in this case. More clinical cases based on molecular diagnosis of the fastidious pathogens need to be accumulated to further understand the characteristics and appropriate treatment regimen.

DOI： 10.1016/j.jiac.2020.09.024

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DOI： 10.1136/postgradmedj-2020-139562

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Primary effusion lymphoma (PEL) is a kind of malignant lymphoma that develops without a tumor mass. A fluid smear is of no use for the diagnosis of miscellaneous condition. Repeated cell-block smear with immunostaining is useful for the diagnosis of PEL.

DOI： 10.1002/ccr3.3469

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Fifteen Klebsiella pneumoniae isolates harbouring blaNDM genes were identified from blood and sputum specimens of patients at a tertiary-care facility (Yangon General Hospital, Yangon, Myanmar) in 2018. Two of the isolates belonged to sequence type (ST) 11, an international high-risk clone. Whole-genome sequencing and phylogenetic analyses revealed that these two isolates were clustered together with other ST11 isolates originating from other countries. The isolates harboured the blaNDM-5 gene on an IncFII-type plasmid that is prevalent among carbapenemase-producing Enterobacteriaceae in Yangon but has rarely been found in other ST11 isolates. Our data suggests the regional presence of the ST11 international high-risk clone and its acquisition of an endemic blaNDM-5-carrying plasmid.

DOI： 10.1099/JMM.0.001348

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Influenza potentially has a high mortality rate when it affects the elderly. We aimed to examine the differences in clinical manifestations in patients with influenza according to their age. This multicenter prospective study was performed in six medical institutions in Okayama and Kagawa prefectures (Japan). Between December 1, 2019 and March 31, 2020, we collected data on adult patients diagnosed with influenza type A, who were strat-ified into younger (20-49 years), middle-aged (50-64 years), and older groups (≥ 65 years). We compared the presence or absence of fever, respiratory symptoms, and extrapulmonary symptoms according to age group. In total, 203 patients (113, younger; 51, middle-aged; and 39, older) were eligible for the analysis. The maxi-mum body temperature and temperature at first physician visit in the older group were significantly lower than those in the younger group. The incidence of respiratory symptoms was not different among the three groups. Chills, muscle pain, and arthralgia as systemic symptoms were noted significantly more frequently in the younger (80.9%) and middle-aged (75.5%) groups than in the older group (51.3%) (p = 0.002). Fever and sys-temic symptoms were less likely to appear in older patients, possibly resulting in the delaying of hospital visits among older adults.

DOI： 10.18926/AMO/62769

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Antimicrobial stewardship for outpatients with acute respiratory tract infections (ARTIs) should be urgently promoted in this era of antimicrobial resistance. Previous large-sample studies were based on administrative data and had limited reliability. We aimed to identify current antimicrobial prescription practices for ARTIs by directly basing on medical records. This multicenter retrospective study was performed from January to December in 2018, at five medical institutes in Japan. We targeted outpatients aged ≥18 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting ARTIs. We divided the eligible cases into three age groups (18-64 years, 65-74 years, and ≥75 years). We defined broad-spectrum antimicrobials as third-generation cephalosporins, macrolides, fluoroquinolones, and faropenem. Primary and secondary outcomes were defined as the proportion of antimicrobial prescriptions for the common cold and other respiratory tract infections, respectively. Totally, data of 3,940 patients were collected. Of 2,914 patients with the common cold, 369 (12.7%) were prescribed antimicrobials. Overall, compared to patients aged ≥75 years (8.5%), those aged 18-64 years (16.6%) and those aged 65-74 years (12.1%) were frequently prescribed antimicrobials for the common cold (odds ratio [95% confidential interval]; 2.15 [1.64-2.82] and 1.49 [1.06-2.09], respectively). However, when limited to cases with a valid diagnosis of the common cold by incorporating clinical data, no statistical difference was observed among the age groups. Broad-spectrum antimicrobials accounted for 90.2% of the antimicrobials used for the common cold. Of 1,026 patients with other respiratory infections, 1,018 (99.2%) were bronchitis, of which antimicrobials were prescribed in 49.9% of the cases. Broad-spectrum antimicrobials were the main agents prescribed, accounting for nearly 90% of prescriptions in all age groups. Our data suggested a favorable practice of antimicrobial prescription for outpatients with ARTIs in terms of prescribing proportions, or quantitative aspect. However, the prescriptions were biased towards broad-spectrum antimicrobials, highlighting the need for further antimicrobial stewardship in the outpatient setting from a qualitative perspective.

DOI： 10.1371/journal.pone.0259633

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DOI： 10.1136/bcr-2020-240075

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DOI： 10.2169/internalmedicine.5374-20

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Alkaline phosphatase (ALP) is an enzyme that is expressed in a variety of tissues. Among the isoforms of ALP, bone-specific alkaline phosphatase (BAP) is used as a marker for evaluating bone metabolism. We investigated the clinical usefulness of the ratio of serum BAP to total ALP for the diagnosis of various disorders in general practice. We retrospectively analyzed the cases of 107 Japanese patients whose serum BAP levels were exam-ined, focusing on clinical characteristics. We observed that the BAP/ALP ratios of the patients with fever and those with inflammatory diseases were significantly lower than the ratios of other patient groups. The BAP/ALP ratios of the patients with osteoporosis and those with metabolic bone diseases were higher than those of the patients with other conditions. The BAP/ALP ratio was found to be negatively correlated with age, a cor-relation that has not been found in other ethnicities. The serum BAP/ALP ratio was inversely correlated with serum CRP levels but was positively correlated with serum albumin levels and hemoglobin concentrations. Collectively, our results suggest that the BAP/ALP ratio could be a useful predictor for important geriatric con-ditions seen in general practice.

DOI： 10.18926/AMO/61205

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We have presented a case of Salmonella-induced infective aortic aneurysm in which the presence of peri-aortic gas was a clue for diagnosis. The disease is clinically infrequent but potentially has a high mortality rate. Clinicians should consider this fatal disease from any trivial findings.

DOI： 10.1002/ccr3.3367

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Septic pulmonary embolism (SPE) is a rare yet serious infectious disorder with nonspecific clinical findings due to microorganism-containing emboli disseminating from extrapulmonary infectious foci. It is unknown whether a positive blood culture correlates with a worse clinical outcome. We compared the clinical and microbiologic characteristics of patients with SPE divided into the culture-positive group and the culture-negative one. This study was a retrospective observational study of the patients diagnosed with SPE and treated in an academic hospital from April 2010 to May 2020. We identified six culture-positive and four culture-negative patients with SPE during the study period. The culture-positive group had significantly longer periods of hospitalization (median: 75 days, range: 45-125 days) than the culture-negative group (median: 14.5 days, range: 3-43 days) (p < 0.05), as well as significantly elevated serum C-reactive protein and procalcitonin. Patients with culture-negative SPE more commonly had odontogenic infections as the primary infectious foci. Our study highlights the importance of giving extra attention to SPE patients who have a positive blood culture, as they may have worse clinical outcomes. Physicians need to collaborate with dentists when faced with patients with culture-negative SPE, since they may have primary odontogenic infections.

DOI： 10.3390/pathogens9120995

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Complications of pheochromocytoma, such as hypertensive emergency, can be critical. Clinicians should recognize that pheochromocytoma is not uncommon in patients with large adrenal tumors, and screening should be undertaken prior to any intervention.

DOI： 10.1002/ccr3.3124

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Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship.

DOI： 10.1016/j.jiac.2020.06.021

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Shewanella sp., the progenitors of blaOXA-48 -like genes are increasingly reported with the possession of different blaOXA-48 -like variants. This study aims to characterize blaOXA-731 , a new variant of a blaOXA-48 -like gene identified in Shewanella sp. isolated from the aquatic environment in Myanmar. Phylogenetic analysis of the blaOXA-731 sequence with other blaOXA-48 -like variants showed that it has the highest nucleotide identity of 86.09% with blaOXA-48 . However, the active site motifs in OXA-731 were 100% identical to that in OXA-48. Whole-genome sequencing analysis showed that blaOXA-731 is not surrounded by any mobile genetic elements. The genetic context of blaOXA-731 was found as similar to other blaOXA-48 -like genes previously identified in Shewanella sp. S1 nuclease pulsed-field gel electrophoresis followed by Southern blotting confirmed the location of blaOXA-731 in the chromosome of the Shewanella genome. Cloning and expression studies showed that OXA-731 has β-lactamase activity similar to OXA-48 and OXA-181, but it has no significant carbapenemase activity. Our results showed the significance of blaOXA-48 -like-carrying Shewanella sp. in the spreading of blaOXA-48 -like genes in the community.

DOI： 10.1111/1758-2229.12875

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TAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.

DOI： 10.1016/j.jiac.2020.06.020

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INTRODUCTION: Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy). METHODS: The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients' baseline hospital admittance status, as intensive care unit or general wards. RESULTS: We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02). CONCLUSION: VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.

DOI： 10.1016/j.jiac.2020.05.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (>= 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=-0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.

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To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (≥ 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=-0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.

DOI： 10.18926/AMO/60797

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER  

Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2020.06.021

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In the era of hyper-ageing, Creutzfeldt-Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005-2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4-5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7-8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.

DOI： 10.1038/s41598-020-72519-0

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DOI： 10.1136/postgradmedj-2019-137328

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Odontogenic infections, generally caused by dental caries and periodontal disease, can result in fatal illness. We herein report a 71-year-old Japanese woman with type 2 diabetes and hemodialysis who suffered from multiple dentofacial abscesses mainly caused by multidrug-resistant Streptococcus oralis. She complained of pain and swelling of her face, with an extraoral fistula from the left cheek. Following 3 surgical debridement procedures and partial mandibulectomy, in addition to 12 weeks of antimicrobial therapy, the multiple dentofacial abscesses were ameliorated. A combination of surgical and antimicrobial treatments following an early diagnosis is essential for reducing further complications.

DOI： 10.2169/internalmedicine.4283-20

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Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BAC-TECT (TM) FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2020.03.004

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Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BACTEC™ FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient.

DOI： 10.1016/j.jiac.2020.03.004

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BACKGROUND: The widespread administration of the Haemophilus influenzae type b vaccine has led to the predominance of non-typable H. influenzae (NTHi). However, the occurrence of invasive NTHi infection based on gynecologic diseases is still rare. CASE PRESENTATION: A 51-year-old Japanese woman with a history of adenomyoma presented with fever. Blood cultures and a vaginal discharge culture were positive with NTHi. With the high uptake in the uterus with 67Ga scintigraphy, she was diagnosed with invasive NTHi infection. In addition to antibiotic administrations, a total hysterectomy was performed. The pathological analysis found microabscess formations in adenomyosis. CONCLUSIONS: Although NTHi bacteremia consequent to a microabscess in adenomyosis is rare, this case emphasizes the need to consider the uterus as a potential source of infection in patients with underlying gynecological diseases, including an invasive NTHi infection with no known primary focus.

DOI： 10.1186/s12879-020-05193-2

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BACKGROUND: Cytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated. AIM: This study aimed to assess the risk of CMV infection among HCWs through daily medical practices. METHODS: Serum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids. FINDINGS: We analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different. CONCLUSION: Our study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding.

DOI： 10.1016/j.jiac.2020.02.011

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BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) infections has been increasing worldwide, becoming a significant healthcare burden especially among elderly people. This study aimed to evaluate the trends in NTM-associated mortality in Japan. METHODS: This study used vital statistics data and data on all NTM-associated deaths (N=18,814) among individuals aged ≥40 years in Japan from 1997 to 2016. We calculated the crude and age-adjusted mortality rates by age and sex and used joinpoint regression to analyze trends and estimate the average annual percentage change (AAPC). We compared crude NTM- and tuberculosis (TB)-associated mortality rates by sex. RESULTS: The overall crude annual mortality rate increased from 0.63/100,000/year in 1997 to 1.93/100,000/year in 2016 and was the highest among individuals aged 80-84 years. The AAPC of the crude mortality rates among males of all ages and females aged 40-59 years were stable but increased among females aged 60-79 years (3.5%, 95% confidence interval [CI]: 2.8-4.3%) and ≥80 years (4.3%, 95% CI: 3.7-4.9%). Among males, the age-adjusted mortality rates did not show a significant trend, while among females, the rates increased over the study period (AAPC: 4.6%, 95% CI: 2.7-6.6%). In females, the crude NTM-associated mortality rate exceeded the TB mortality rate in 2014, 2015, and 2016. CONCLUSIONS:  NTM mortality increased in Japan between 1997 and 2016, especially among the elderly female population. Given the increasing NTM-associated mortality and susceptible aging population, public health authorities in Japan should pay greater attention to NTM infections.

DOI： 10.1093/cid/ciaa810

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OBJECTIVES: Appropriate antibiotic prescriptions for outpatients with acute respiratory tract infections (ARTIs) are urgently needed in Japan. However, the empirical proof of this need is under-documented. Therefore, we aimed to determine antibiotic prescription rates, and the proportions of antibiotic classes prescribed for Japanese patients with ARTIs. METHODS: We analysed health insurance claims data over 2013-2015 among Japanese patients aged <75 years and determined the following indicators: 1) visit rates for patients with ARTIs and antibiotic prescription rates per 1000 person-years, and 2) proportion of visits by antibiotic-prescribed patients with ARTIs. We defined broad-spectrum antibiotics using the WHO Anatomical Therapeutic Chemical classification 4 level codes. RESULTS: Among 8.65 million visits due to ARTIs at 6859 hospitals and 62,024 physicians' offices, the visit rate and antibiotic prescription rate per 1000 person-years were 990.6 (99% confidence interval [CI], 989.4-991.7) and 532.4 (99% CI, 531.6-533.3), respectively. The visit rates for patients aged 0-17, 18-59, and 60-74 years were 2410.0 (99% CI, 2407.2-2412.9), 683.6 (99% CI, 682.7-684.6), and 682.1 (99% CI, 678.2-686.0), and antibiotic prescription rates were 1093.3 (99% CI, 1091.4-1095.2), 434.1 (99% CI, 433.4-434.9), and 353.4 (99% CI, 350.7-356.1), respectively. The overall proportion of antibiotic prescriptions for ARTI visits was 52.7% and 91.3% of the antibiotics prescribed were broad-spectrum. CONCLUSIONS: Both the visit rates and antibiotic prescription rates for ARTIs were high in this Japanese cohort. The proportion of antibiotic prescriptions exceeded that recommended in the clinical guidelines. Thus, there might be a scope for reducing the current antibiotic prescription rate in Japan.

DOI： 10.1016/j.jiac.2020.02.001

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DOI： 10.2169/internalmedicine.3507-19

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Language：Japanese   Publisher：(公社)日本薬学会  

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A 69-year-old Japanese man with a 10-year history of hemodialysis for end-stage renal disease presented with painful necrosis of the fingers of his right hand. A plain radiograph of the right hand revealed severely calcified arteries, particularly in the ring finger, suggesting the diagnosis of calciphylaxis of the fingers.

DOI： 10.1002/jgf2.296

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Background:
Globally, the number of deaths is estimated to increase to 74 million per year by 2030. Place of death (PoD) is increasingly being recognized as an important aspect of end-of-life care. However, recent trends in PoD in Japan, one of the super-aged societies, are unknown.
Objective:
To analyze trends in PoD in Japan over two decades.
Design:
Population-based retrospective observational study.
Setting:
All deaths reported in Japan, 1998-2017. PoD was defined as hospital, nursing home, or own home.
Results:
All Japanese decedents (∼22.6 million) over the past 20 years were analyzed. The proportion of hospital deaths was consistently high (>80%), with a significant decreasing trend from the mid-2000s. Although the proportion of deaths at home decreased in the first half of the study period, they later increased. There was a low proportion of deaths in nursing homes compared to other places of death; however, the proportion increased continually throughout the study period, particularly among women. In 2015, more women died in nursing homes than at home. Although the proportion of hospital deaths declined in the second half of the study period, their overall number continued to increase, reflecting an increase in total deaths in Japan.
Conclusions:
This study highlighted rapid changes in trends in PoD in Japan, and the need to consider affordable end-of-life care in Japan as well as other countries with aging populations. The findings from this long-term epidemiological study provide important insights on this issue.

DOI： 10.1089/jpm.2019.0445

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DOI： 10.2169/internalmedicine.3121-19

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A relationship between diabetes and depression is apparent. To clarify the clinical relevance of diabetic patients' gastroesophageal symptoms to their psychological status, we retrospectively analyzed the data from a Selfrating Depression Scale (SDS) and a Frequency Scale for Symptoms of Gastroesophageal reflux disease (FSSG) among 143 type 2 diabetic patients who visited a general medicine department. Among the 45 Japanese patients enrolled, the group with relatively high SDS scores (≥ 36) showed higher (FSSG) dysmotility symptom scores versus the low-SDS (< 36) group, although the 2 groups' characteristics and laboratory data were not significantly different. Positive correlations of postprandial plasma glucose (PPG) levels with FSSG scores (R=0.321, p<0.05), particularly with reflux scores (R=0.455, p<0.01) were revealed. PPG and HbA1c levels were not correlated with SDS scores. The patients' SDS scores were significantly correlated with their FSSG scores (R=0.41, p<0.01), suggesting that depressive status is linked to GERD-related manifestations. Considering that the patients' PPG levels were correlated with GERD-related symptoms, diabetic patients' blood glucose levels are associated with depressive status. Collectively, key symptoms related to GERD and glucose level values would be helpful.

DOI： 10.18926/AMO/57950

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BACKGROUND: Limited treatment options complicate management of infections with New Delhi metallo-β-lactamase (NDM)-producing organisms. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against NDM-producing Enterobacteriaceae. MATERIALS AND METHODS: Twelve E. coli clinical isolates harbouring blaNDM-1 along with a positive control E. coli BAA-2469 harbouring blaNDM-1 were studied. Minimum inhibitory concentrations (MICs) of MEM, ertapenem (ERT), and CMZ were determined by broth microdilution. Checkerboard and time-kill assays were performed to confirm the in vitro efficacy of the MEM/CMZ combination. Scanning electron microscopy, kinetic studies, and whole genome sequence analysis were used to determine the antimicrobial resistant mechanisms. RESULTS: MICs of MEM, ERT, and CMZ in monotherapy ranged from 8 to 32, 16 to 128, and 32 to 512 μg/mL, respectively. In checkerboard, MEM/ERT resulted in no synergy, whereas MEM/CMZ showed a synergistic effect in all the tested isolates. Furthermore, the MIC of MEM in combination decreased by 2- to 8-fold compared to that of MEM alone. The time-kill study revealed a bactericidal effect in 4 out of 13 isolates at 24 hours. Scanning electron microscopy showed spheroidisation of the bacterial cell in the MEM/CMZ combination, which was not observed in single antibiotic conditions. The kinetic studies indicated a better activity of CMZ to ERT as an antagonist for NDM-1. Whole genome sequence analysis did not reveal any explainable differences between isolates susceptible to the combination therapy and those not susceptible to combination therapy. CONCLUSION: In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.

DOI： 10.1016/j.ijantimicag.2020.105905

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DOI： 10.6009/jjrt.2020_JSRT_76.9.965

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01192&link_issn=&doc_id=20200930490009&doc_link_id=130007906098&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007906098&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

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Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

DOI： 10.1038/s41598-019-56388-w

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OBJECTIVES: Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. DESIGN: We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. RESULTS: The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. CONCLUSIONS: Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.

DOI： 10.1136/bmjopen-2019-033462

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Corynebacterium striatum, generally considered an opportunistic organism in humans, has recently been known to develop high-level daptomycin resistance (HLDR) shortly after drug exposure. To date, however, only several such clinical isolates have been described in the literature and clinical background of the resistant pathogen remains to be elucidated. Here, we report a case involving a C. striatum strain with HLDR harboring novel nucleotide mutations, together with a review of the relevant literature. To the best of our knowledge, this is the first well-investigated clinical report from Japan including a genetic investigation. Considering the rapid emergence of HLDR C. striatum in vitro experiment, there could be a number of underreporting cases. Scrupulous attention is required when administering daptomycin for the treatment of C. striatum infections, even if the organism has initially exhibited susceptibility.

DOI： 10.1016/j.jiac.2019.04.009

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OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). RESULTS: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

DOI： 10.1186/s13104-019-4779-x

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DOI： 10.7754/Clin.Lab.2019.190324

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Despite being an established method to identify the unilateral subtype of primary aldosteronism with an indication of adrenalectomy, adrenal venous sampling sometimes fails primarily due to unsuccessful cannulation to adrenal veins. In such cases, the analysis of clinical findings might help to identify the indication of surgery.

DOI： 10.1002/ccr3.2317

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Patients with measles or rubella infections manifest acute onset fever accompanying systemic exanthema, which are clinically difficult to be distinguish. Rapid diagnosis and differentiation of such epidemic viral diseases is essential to prevent outbreaks. We developed a single-tube multiplex real-time PCR assay for these indistinguishable viruses. We used previously-reported primer settings, with a slight modification of reporter dye, and applied to multiplex Taqman real-time PCR by cobas z480 (Roche Molecular Systems, Inc.). Consequently, the assay could detect 10 copies/10 μl of measles and rubella with coefficient of variations of 11.2% and 21.8%, respectively. Strengths of our methodology include simplicity of operation, short measurement time (2 h), uses of internal control (confirming a run of PCR), and quantitative measurement with high sensitivity. Both measles and rubella currently cause social outbreaks in Japan. We hope that our single-tube multiplex assay contributes to an early diagnosis, leading to an appropriate infection control measure and prevention of epidemics.

DOI： 10.1016/j.jiac.2019.05.005.

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The spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a serious threat to clinical practice and public health. These bacteria are present both in clinical settings and non-clinical environments. The presence of CPE in food stuffs has been reported, but sporadically so. Here, we screened for CPE in meat, seafood, and vegetable samples from local markets of Yangon, Myanmar. We obtained 27 CPE isolates from 93 food samples and identified 13 as Escherichia coli, six as Klebsiella pneumoniae, seven as Enterobacter cloacae complex, and one as Serratia marcescens. All except the E. cloacae complex harboured the carbapenemase genes blaNDM-1 or blaNDM-5, while all Enterobacter isolates carried the carbapenemase gene blaIMI-1. The blaIMI-1 gene was located in putative mobile elements EcloIMEX-2, -3, or -8. Using multi-locus sequence typing, E. coli, K. pneumoniae, and E. cloacae complex isolates were classified into 10, six, and five different sequence types, respectively. Our results demonstrate that diverse organisms with various carbapenemase genes are widespread in the market foods in Yangon, highlighting the need for promoting proper food hygiene and effective measures to prevent further dissemination.

DOI： 10.1038/s41598-019-51002-5

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Objective The importance of antimicrobial stewardship is increasingly highlighted in this age of antimicrobial resistance. A better comprehension of adverse drug events (ADEs) can promote the appropriate use of antibiotics. We aimed to quantify the incidence of ADEs associated with broad-spectrum systemic antibiotics in a hospital setting. Methods We conducted a six-month prospective, observational study at Osaka University Hospital to describe the incidence of ADEs in patients hospitalized in general wards undergoing treatment with broad-spectrum antibiotics [carbapenems, piperacillin/tazobactam (PIPC/TAZ), and anti-methicillin-resistant Staphylococcus aureus agents]. The occurrence of ADE was defined as any cardiac, gastrointestinal, hepatobiliary, renal, neurologic, hematologic, dermatologic, or musculoskeletal manifestation after 48 hours or more of systemic antibiotic therapy. Results The 3 most frequently prescribed antibiotics were PIPC/TAZ (242 cases), meropenem (181 cases), and vancomycin (92 cases). Of 689 patients, 118 (17.1%) experienced ADEs, including gastrointestinal (6.4%), hepatobiliary (4.2%), dermatologic (2.5%), and renal (2.3%) manifestations. Patients treated with PIPC/TAZ, meropenem, doripenem, vancomycin, daptomycin, and teicoplanin developed ADEs at rates of 20.7%, 16.0%, 15.4%, 19.6%, 11.8%, and 10.9%, respectively. Conclusion Our study provides a quantitative value for the incidence of ADEs associated with broad-spectrum antibiotics in clinical practice. To optimize patient safety, clinicians need to be aware of the risks associated with antibiotic administration.

DOI： 10.2169/internalmedicine.2603-18

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DOI： 10.1111/1346-8138.14864

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© 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Background: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. Purpose: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. Methods: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. Results: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. Conclusions: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

DOI： 10.1093/fampra/cmy094

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Mycobacterium kansasii is one of the major non-tuberculous mycobacteria species that typically cause pulmonary diseases. M. kansasii is known to cause septic arthritis as an extrapulmonary disease in immunosuppressed patients or chronic skin disease. Herein, we present a case of M. kansasii arthritis involving the elbow of an immunocompetent patient, which was initially suspected to be a soft-tissue tumor. A 70-year-old man presented with a swollen left elbow that had progressed for 18 months with deteriorating arthralgia and limited range of motion. Magnetic resonance imaging revealed filling of the intra-articular space of the elbow and surrounding of the radial head with a soft tissue mass with mixed signal intensity. Initial incisional biopsy was performed via the lateral approach to the elbow joint, and pathological examination of the mass did not reveal any evidence of malignancy. One year after the first operation, arthroscopic surgery was performed to excise the mass following the recurrence of swelling and limited function of the elbow. Pathological examination of the resected synovium revealed epithelioid granulomas containing a multinucleated giant cell and inflammatory cell infiltration, characteristic of mycobacterial infection. M. kansasii was cultured after 2 weeks of incubation of the synovial sample. He experienced full resolution of the swelling and limited function following a combination of synovectomy and multidrug antimycobacterial treatment (rifampin 600 mg/day, clarithromycin 800 mg/day, and ethambutol 750 mg/day). This case highlights the need to consider this rare infection in the differential diagnosis of intra-articular soft tissue tumor-like lesions even in immunocompetent patients.

DOI： 10.1016/j.jiac.2019.07.015

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BACKGROUND: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. PURPOSE: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. METHODS: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. RESULTS: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. CONCLUSIONS: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

DOI： 10.1093/fampra/cmy094

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Blood culture is the most critical examination for diagnosing bacterial infections. The longer the blood culture incubation period, the higher the chances of identifying bacterial strains. However, unnecessary extension of the incubation period can burden the capacity of the instrument and merely result in the detection of contaminant bacteria having no clinical significance. This study aimed to optimize the blood culture incubation period using the currently available continuous-monitoring automated blood culture instrument. This was a 2-year retrospective study performed at Osaka University Hospital (January 1, 2016 to December 31, 2017). The BD BACTEC™ FX blood culture system (Becton Dickinson, Sparks, MD, USA) and BD BACTEC™ Plus series blood culture bottles were used. All blood cultures were incubated for more than 12 consecutive days. We reviewed the clinical data of cases that tested positive between 6 and 12 days of incubation. During the study period, 14,822 sets of blood culture were drawn. Of 1751 sets testing positive, 95.7% (1665 sets) became positive within 5 days of incubation. The overall contamination rate (false positives) after 6 days of incubation was 80.2% (69/86 sets). Based on the positive blood culture results, antimicrobials were changed in 7.0% (6/86) of the sets, and a diagnosis of infectious disease was made in only one case. There was no death associated with the extended blood culture results. In conclusion, the clinical impact of extended blood culture incubation for 6 days or more was limited, and a routine extension of the incubation period might be unnecessary.

DOI： 10.1016/j.jiac.2019.03.001

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DOI： 10.1089/mdr.2018.0397

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We herein describe an irregular case of toxic-shock syndrome (TSS). A previously healthy 28-year-old Japanese man developed a sudden-onset high fever. The patient was suffering from conjunctival hyperaemia, gastrointestinal symptoms such as vomiting and diarrhoea, and systemically diffused macular erythroderma. Further physical examination detected pustules on his back, which self-destructed over time. Laboratory revealed multiple organ failures. Subsequently, scalded skin on the face and desquamation in the limb extremities emerged by day 10, leading to the diagnosis of TSS, despite his stable circulatory dynamics through the course. Learning points for clinicians include that they should recall TSS as a possible disease concurrently causing high fever, systemic rash and multiple organ dysfunctions, even without being in a state of shock. The characteristic desquamations emerged in the limb extremities after hospitalisation were of help in diagnosing TSS.

DOI： 10.1136/bcr-2019-229610

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Background: Active surveillance has the potential to prevent nosocomial transmission of carbapenem-resistant Acinetobacter baumannii (CRAB). We assessed whether rapid diagnosis using clinical specimen-direct loop-mediated isothermal amplification (LAMP), a rapid molecular diagnostic assay, and subsequent intervention, could reduce CRAB nosocomial transmission in intensive care units (ICUs). Methods: A before and after (quasi-experimental) study was conducted in two ICUs at the Mahidol University Faculty of Medicine Ramathibodi Hospital with 3 months of observational period followed by 9 months of interventional period. All patients were screened for CRAB using both the culture and LAMP method from rectal swab and/or bronchial aspirates (intubated patients only) upon admission, weekly thereafter, and upon discharge. During the pre-intervention period, we performed contact precautions based on culture results. In contrast, during the intervention period, we initiated contact precautions within a few hours after sample collection on the basis of LAMP results. Results: A total of 1335 patients were admitted to the ICUs, of which 866 patients (pre-intervention period: 187; intervention period: 679) were eligible for this study. Incidence rate of CRAB infection decreased to 20.9 per 1000 patient-days in the intervention period from 35.2 in the pre-intervention period (P < 0.02). The calculated hazard ratio of CRAB transmission was 0.65 (95% confidence interval [CI], 0.44-0.97). Risk factors for CRAB acquisition included exposure to carbapenem (hazard ratio, 2.54 [95% CI: 1.61-5.57]). Conclusions: LAMP screening for CRAB upon ICU admission proved feasible for routine clinical practice. Rapid screening using LAMP followed by early intervention may reduce CRAB transmission rates in ICUs when compared to conventional intervention.

DOI： 10.1186/s13756-019-0564-9

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Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.

DOI： 10.1016/j.jiac.2018.12.009

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INTRODUCTION: To promote antimicrobial stewardship activity, an understanding of the incidence of antibiotic-associated adverse drug events (ADEs) is essential. In this study, we aimed to describe the occurrence of antibiotic-associated ADEs at our hospital. METHODS: We retrospectively searched the ADE registration system in Osaka University Hospital between 2010 and 2017. Registrations of ADEs were dependent on the patients' drug history and clinical course after hospitalization. We classified the data according to types of ADEs (gastrointestinal, hepatobiliary, renal, cardiac, respiratory, hematologic, neurologic, dermatologic, and musculoskeletal) and antibiotic class. RESULTS: During the study period, we found 707 cases of antibiotic-associated ADEs, accounting for 22.3% of all the cases. Beta-lactam antibiotics constitute more than half of the cases (51.3%). The most common ADE was dermatologic abnormalities (53.4%), followed by liver dysfunction (9.7%) and gastrointestinal symptoms (8.9%). Among all antibiotics, oral third-generation cephalosporins were frequently reported as offending drugs (107 cases), accounting for 29.5% of beta-lactam ADEs and 46.3% of cephem ADEs. CONCLUSION: Antibiotic-associated ADEs covered approximately 20% of all the ADEs at our hospital. We believe that the data would be helpful in ensuring patient safety by promoting antimicrobial stewardship in hospitals.

DOI： 10.1016/j.jiac.2018.11.002.

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The application and clinical impact of rapid antigen detection test (RADT) in the treatment of acute pharyngitis is unknown in Japan. We aimed to examine the proportions of RADT usage to identify Group A β-hemolytic Streptococcus (GAS) in outpatients with acute pharyngitis and evaluate the association between RADT and antibiotic treatment. We analyzed health insurance claims data from 2013 to 2015. Logistic regression models were used to analyze associated factors with RADT, overall antibiotic prescription, or penicillin use. We analyzed 1.27 million outpatient visits with acute pharyngitis, in which antibiotics were prescribed in 59.3% of visits. Of the total visits, 5.6% of patients received RADT, and 10.8% of the antibiotics were penicillin. Penicillin selection rates were higher in cases with RADT (25.4%) than those without RADT (9.7%). Compared to large-scale facilities, antibiotic prescription rates were higher in physicians' offices. For factor analysis, age (3-15 years), diagnosis code (streptococcal pharyngitis), size of the medical facility (large-scale hospitals), and physician's specialty (pediatrics) were associated with RADT use. Penicillin selection rate increased with RADT implementation (25.4% vs. 9.7%: adjusted odds ratio 1.55; 95% CI, 1.50-1.60). At 63% of the facilities, the RADT implementation rate was <5% of acute pharyngitis visits prescribed antibiotics. In conclusion, the proportion of RADT usage for outpatients with acute pharyngitis was low in Japan. With appropriate indication and evaluation, we expect that more utilization of RADT can help promote antimicrobial stewardship for outpatients with acute pharyngitis by prompting penicillin therapy. Further investigation with detailed clinical data are warranted.

DOI： 10.1016/j.jiac.2018.12.005

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DOI： 10.2169/internalmedicine.1900-18

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DOI： 10.1136/bcr-2018-228290

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The spread of carbapenemase-producing Enterobacteriaceae (CPE), contributing to widespread carbapenem resistance, has become a global concern. However, the specific dissemination patterns of carbapenemase genes have not been intensively investigated in developing countries, including Myanmar, where NDM-type carbapenemases are spreading in clinical settings. In the present study, we phenotypically and genetically characterized 91 CPE isolates obtained from clinical (n = 77) and environmental (n = 14) samples in Yangon, Myanmar. We determined the dissemination of plasmids harboring genes encoding NDM-1 and its variants using whole-genome sequencing and plasmid analysis. IncFII plasmids harboring bla NDM-5 and IncX3 plasmids harboring bla NDM-4 or bla NDM-7 were the most prevalent plasmid types identified among the isolates. The IncFII plasmids were predominantly carried by clinical isolates of Escherichia coli, and their clonal expansion was observed within the same ward of a hospital. In contrast, the IncX3 plasmids were found in phylogenetically divergent isolates from clinical and environmental samples classified into nine species, suggesting widespread dissemination of plasmids via horizontal transfer. Half of the environmental isolates were found to possess IncX3 plasmids, and this type of plasmid was confirmed to transfer more effectively to recipient organisms at a relatively low temperature (25°C) compared to the IncFII plasmid. Moreover, various other plasmid types were identified harboring bla NDM-1, including IncFIB, IncFII, IncL/M, and IncA/C2, among clinical isolates of Klebsiella pneumoniae or Enterobacter cloacae complex. Overall, our results highlight three distinct patterns of the dissemination of bla NDM-harboring plasmids among CPE isolates in Myanmar, contributing to a better understanding of their molecular epidemiology and dissemination in a setting of endemicity.

DOI： 10.1128/AAC.01924-18

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DOI： 10.1136/bcr-2018-228847

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Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types-IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (<2 h) and robust sensitivity (100%)/specificity (~99%) of PCR-dipstick show that this specimen-direct screening method could aid in implementing infection control measures at the earliest to control the dissemination of MCRPEn and CPE.

DOI： 10.3389/fmicb.2019.00149

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DOI： 10.1136/bcr-2018-228888

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DOI： 10.2169/internalmedicine.1127-18

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Staphylococcus aureus as a pathogen in human gestational membranes, a rather rare phenomenon, has recently been the focus of several researches. S. aureus forms biofilms on these membranes and potentially causes chorioamnionitis in pregnant women. We report a case of persistent methicillin-resistant S. aureus (MRSA) bacteremia owing to placental infection, causing chorioamnionitis and preterm birth. A 29-year-old Japanese woman at the 27th gestational week was diagnosed with acute promyelocytic leukemia and underwent all-trans retinoic acid therapy. Soon after hospitalization, the patient presented with persistent MRSA bacteremia of unknown origin. Despite various antimicrobial therapies, she experienced 12 MRSA bacteremia episodes over 6 weeks. However, after child birth, MRSA bacteremia disappeared without any complications. A pathologic examination of her placenta revealed placenta abscess, resulting in a diagnosis of MRSA-associated chorioamnionitis. Molecular analysis proved that a single MRSA strain (SCCmec Type IVa), which tested negative for Panton-Valentine leukocidin and toxic shock syndrome toxin-1, caused the obstinate infection. We should be aware that persistent MRSA bacteremia in pregnant women can originate from placental abscess.

DOI： 10.1016/j.jiac.2018.05.001

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DOI： 10.1016/j.amjmed.2018.08.007

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OBJECTIVES: To describe and examine trends in polypharmacy according to age in Japan from 2010 to 2016. DESIGN: Retrospective observational study. SETTING: Outpatient settings. PARTICIPANTS: Japanese individuals aged 20 and older. MEASUREMENTS: We analyzed pharmacy claims data that the Japanese Ministry of Health, Labor, and Welfare provided in the Survey of Medical Care Activities in Public Health Insurance from 2010 to 2016. The use of 5 or more oral prescription medications per month was defined as polypharmacy and of 10 or more as excessive polypharmacy. Regression analysis was used to estimate trends in polypharmacy with annual percentage changes. Using number of medications (polypharmacy vs excessive polypharmacy), trends in polypharmacy and crude and age-adjusted rates of polypharmacy per 1,000 persons were calculated according to year and age group (20-34, 35-49, 50-64, 65-79, ≥ 80). RESULTS: We analyzed 240 million pharmacy claims data. The age-adjusted monthly prevalence rate of polypharmacy increased from 85.2 to 93.8 per 1,000 persons per month and of excessive polypharmacy from 13.6 to 14.0 per 1,000 persons per month from 2010 to 2016 in the entire study population. The highest rate of polypharmacy (per 1,000 persons) was observed in 2016 in those aged 80 and older (326.8), followed by those aged 65 to 79 (167.3). The polypharmacy rate increased by 6.3% (95% confidence interval (CI)=4.0-8.7) per year from 2010 to 2012, then decreased by 0.7% (95% CI=-1.3-0.0) per year from 2012 to 2016. The rate of excessive polypharmacy increased by 4.5% (95% CI=1.1-8.0) per year from 2010 to 2013 and then decreased by 3.7% (95% CI=-6.7 to -0.6) per year from 2013 to 2016. CONCLUSION: The overall trend of polypharmacy in Japan increased during the study period, although the increase ceased in 2013 and then declined from 2013 to 2016. Policy changes in Japan might be responsible for some of the changes. J Am Geriatr Soc 66:2267-2273, 2018.

DOI： 10.1111/jgs.15569

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DOI： 10.1136/bcr-2018-228383

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RATIONALE: Daptomycin (DAP) is a key drug for treating severe Staphylococcus infections. The emergence of DAP non-susceptible Staphylococcus aureus has been widely recognized in clinical situations, although the clinical status of DAP non-susceptible coagulase-negative Staphylococcus (CoNS) infections is unclear. We encountered 2 cases of cardiovascular device infections that were associated with DAP non-susceptible CoNS. PATIENT CONCERNS: The first case involved a 60-year-old woman with a pump pocket infection in a left ventricular assist device. DAP non-susceptible Staphylococcus capitis subsp. ureolyticus was isolated from a blood culture after treatment using vancomycin (10 days) and DAP (6 days). The second case involved a 71-year-old man with an aortic graft infection. DAP non-susceptible S capitis subsp. ureolyticus was detected in pus after treatment using vancomycin (2 weeks) and DAP (1 week) without complete removal and debridement. DIAGNOSIS: Cardiovascular device infections caused by DAP non-susceptible CoNS. INTERVENTIONS AND OUTCOMES: Whole genome sequencing of these strains revealed multiple mutations in genes that are related to DAP-non-susceptibility in S aureus, which created amino acid substitutions in mprF, dltAB, dltD, rpoC, yycG, cls2, pgsA, and vraSR. To the very best of our knowledge, the substitution patterns were not identical to those previously reported in DAP non-susceptibile S aureus. LESSONS: Clinicians should be cautious regarding the emergence of DAP non-susceptible CoNS, especially in cases with implanted prosthetic devices, inadequate debridement, and prior usage of vancomycin and DAP. Further studies are needed to understand the relevance of these genetic changes and DAP-non-susceptibility in CoNS strains.

DOI： 10.1097/MD.0000000000013487

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DOI： 10.1007/s15010-018-1252-z

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Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

DOI： 10.1017/S095026881800290X

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In order to investigate prescribing patterns of in-hospital broad-spectrum antibiotics (antimeticillin-resistant Staphylococcus aureus drugs, carbapenems and piperacillin/tazobactam), data on the distribution of antibiotic initiation and discontinuation throughout the week were analysed at Osaka University Hospital, Japan. No significant differences in the number of initiations were found between weekdays. However, broad-spectrum antibiotics were disproportionately discontinued on Tuesdays or on the second day after a holiday. This study suggests that broad-spectrum antibiotics tend to be continued over weekends or holidays and discontinued thereafter; this is likely to be due to behavioural factors beyond medical indications, and needs to be addressed in future antimicrobial stewardship initiatives.

DOI： 10.1016/j.jhin.2018.11.004

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Roseomonas species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of Roseomonas mucosa bacteremia that involved a 9-year-old Japanese boy who was in a condition of febrile neutropenia caused by chemotherapy for cerebellar medulloblastoma. Conventional phenotyping failed to identify the organism; however, genetic analysis using 16S rDNA sequencing confirmed the pathogen to be R. mucosa. The patient recovered following treatment by meropenem without any complications. A literature review of pediatric cases of Roseomonas bacteremia identified 12 other documented cases, and these revealed that a common clinical situation for the infection is an immunocompromised state with malignancy and/or an indwelling intravenous catheter. Because of the low number of cases, the overall picture of Roseomonas bacteremia in children remains to be elucidated; however, the prognosis of the infection appears to be satisfactory.

DOI： 10.1016/j.idcr.2018.e00469.

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DOI： 10.1136/bcr-2018-227185

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BACKGROUND: With the improvement in sanitation and hygiene, the incidence of hepatitis A virus (HAV) infection has declined, and its seroprevalence among Japanese people has been reduced. Universal HAV vaccination is yet to be implemented in Japan, and the healthcare workers (HCWs) are at higher risks of acquiring this infection. We herein report the seroepidemiology of HAV infection among HCWs at Osaka University Hospital. METHODS: Between September and October 2017, we collected serum samples submitted to our laboratory for HCWs health examination and tested for the anti-HAV antibody. RESULTS: Overall HAV seropositivity rate was 5.1% (22/436 samples). The seroprevalence was higher among those in the twenties (6.0%) and thirties (8.0%), compared to older age groups. CONCLUSIONS: In this age of internationalization, the decreasing immunity for HAV places HCWs at risk of developing the disease. As a preventive measure against occupational infection, HAV vaccination may be needed for Japanese HCWs.

DOI： 10.7754/Clin.Lab.2018.180518

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DOI： 10.1111/jgs.15569

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An NDM-5-producing Klebsiella pneumoniae ST147 strain was isolated from a Japanese patient who had not travelled abroad in at least 5 years. Whole-genome sequencing revealed a genomic rearrangement in an FII plasmid harbouring bla due to the replicative transposition of IS26. A hypothetical structure was proposed for its ancestral plasmid, and comparative genomic analysis of the plasmid suggested the dissemination of structurally similar plasmids harbouring bla in Asian and Middle Eastern countries. NDM-5 NDM-5

DOI： 10.1099/jmm.0.000817

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Pasteurella multocida, a zoonotic pathogen in humans, is known to be associated with skin and soft tissue infections following animal bites, but rarely causes visceral infections. We report a case of P. multocida-associated multiple intrapelvic abscesses in a young woman with uterine cervical cancer. A 29-year-old unmarried woman was referred to us because of prolonged high fever accompanying abdominal pain with muscular guarding. She had a domestic cat but denied of any bites or scratches before that. Computed tomography demonstrated ascites and multiple abscesses around her uterus. Her condition did not improve with an initial treatment with flomoxef, clindamycin, and azithromycin. Further, we performed percutaneous pus drainage and switched the antimicrobial therapy to a combination of piperacillin/tazobactam and minocycline for 10 days. Although P. multocida was isolated from vaginal culture, no organisms were isolated from the pus culture. However, further investigation with specimen-direct 16S rDNA analysis diagnosed P. multocida as possibly a single pathogen responsible for the intrapelvic infection. After taking oral levofloxacin for two weeks, no recurrence was reported. Although P. multocida is known as an animal-related pathogen, it can transmit to humans without apparent bites or scratches. The present case illustrates that P. multocida can cause intrapelvic abscess as a result of ascending genital infection.

DOI： 10.1016/j.jiac.2018.07.019

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DOI： 10.1099/jmm.0.000817.

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DOI： 10.1099/jmmcr.0.005155

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Healthcare workers (HCWs) are at an increased risk of being exposed to epidemic viral diseases (EVDs), such as measles, rubella, mumps, and varicella-zoster. Currently, in case of the absence of written records on previous immunizations, the Japanese Society for Infection Prevention and Control guidelines require HCWs to have antibody titers higher than laboratory thresholds, possibly leading to over-immunization. We report our vaccination strategy and the consequent incidences of EVDs at the Osaka University Hospital between 2000 and 2016. In 2001, we initiated an annual serology check of antibody titers against EVDs and immunization for newly employed HCWs. As an additional vaccination program, all HCWs with low antibody titers were vaccinated in 2005 and 2010. Antibody titers were determined by an enzyme immunoassay (EIA), with a positive range of >2.0 cut-off index. After implementing the vaccination strategy to keep the laboratory threshold, there were only sporadic cases of EVDs among HCWs. More than 99% of individuals who had positive titers in 2005 remained the positive antibody titers in 2010, indicating that a minimum interval of 5 years is enough to measure immunity. Unprotected workers can, even silently, transmit the contagious viruses to patients and coworkers, possibly resulting in a nosocomial outbreak. However, over-vaccination may yield adverse effects and financial burdens. Our observational data indicate that the laboratory cut-off index of >2.0 by EIA may provide a sufficient herd immunity to prevent EVDs among HCWs.

DOI： 10.1016/j.jiac.2018.07.008

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A 65-year-old Japanese man with bilateral carotid atherosclerosis presented with right neck pain and fever. Contrast-enhanced computed tomography suggested carotid arteritis, and carotid ultrasonography showed an unstable plaque. The patient developed a cerebral embolism, causing a transient ischemic attack. Helicobacter cinaedi was detected in blood culture, and H. cinaedi-associated carotid arteritis was diagnosed. Empirical antibiotic therapy was administered for 6 weeks. After readmission for recurrent fever, he was treated another 8 weeks. Although the relationship between H. cinaedi infection and atherosclerosis development remains unclear, the atherosclerotic changes in our patient's carotid artery might have been attributable to H. cinaedi infection.

DOI： 10.18926/AMO/55861

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We describe a rare case of Propionibacterium acnes native-valve endocarditis that silently progressed in a 67-year-old man with hybrid dialysis. The patient was scheduled for kidney transplantation, and pre-operative investigation incidentally detected a vegetative structure at his native mitral valve that had increased in size. He underwent cardiac surgery and P. acnes was detected in cultures of a resected cardiac valve specimen and blood. This case highlights that P. acnes can silently cause infective endocarditis in a native-valve, and that physicians should consider the possibility of infection when P. acnes is isolated in blood cultures.

DOI： 10.2169/internalmedicine.9833-17

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Language：Japanese   Publishing type：Research paper (other academic)  

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Desulfovibrio spp. are sulfate-reducing, anaerobic bacteria that are ubiquitously found in the environment. These organisms infrequently cause human infections, and the clinical characteristics of infection with Desulfovibrio spp. remain unclear. Here, we describe a case of Desulfovibrio desulfuricans bacteremia in an 88-year-old Japanese man with a past medical history of thoracic endovascular aortic repair (TEVAR). His chief complaint was hemoptysis for 2 weeks. A chest contrast-enhanced computed tomography demonstrated an enlarged thoracic aortic aneurysm surrounded by a ring-enhanced lesion, recognized as mediastinal abscess. Gram-negative spiral bacilli were detected in anaerobic blood culture. These bacteria could not be identified using conventional methods, but by analyzing a full base sequence of 16S rDNA, they were identified as D. desulfuricans subsp. desulfuricans. The patient underwent an emergent re-TEVAR, and the infection subsided after being treated with tazobactam/piperacillin and clindamycin, followed by metronidazole. A literature review of previous cases of D. desulfuricans bacteremia suggested that the pathogen was derived from bacterial translocation from the intestine in most cases. Desulfovibrio infection is presumably underestimated due to its infrequency, indolent growth, and difficulty in identification. Desulfovibrio spp. should be suspected when spiral rods are observed in anaerobic culture, and molecular analysis is required for accurate species-level differentiation of the pathogens. To better understand the pathogenicity of these fastidious organisms, further cases based on the exact bacterial identification should be investigated.

DOI： 10.1016/j.anaerobe.2017.12.013

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We herein report a case of recurrent Campylobacter coli bacteremia in a 37-year-old Japanese man with X-linked agammaglobulinemia (XLA). The patient experienced seven episodes of C. coli bacteremia over one year, with an erythematous rash intermittently emerged on the lower limbs. Although hospitalization for intravenous treatment was repeatedly recommended, he obstinately declined it. Following long-term oral antibiotic treatment with tebipenem and faropenem for the persistent infection, C. coli showed elevated minimum inhibitory concentrations to meropenem, a key drug for severe campylobacteriosis. Physicians should note that the overuse of antibiotics can lead to the emergence of carbapenem-non-susceptible Campylobacter strains.

DOI： 10.2169/internalmedicine.0312-17

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DOI： 10.2169/internalmedicine.0312-17

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a leading problem in health care facilities worldwide. Methods: This single-center retrospective cohort study consisted of a derivation phase and a validation phase. The derivation phase included all patients admitted to Osaka University Hospital between May 2010 and April 2011. We proposed a provisional available, bed-sided, comprehensive (ABC) score, and evaluated its accuracy using the clinical diagnosis as a reference. We subsequently revised ABC scores based on k coefficient scores of each variable this revision was validated by applying it to another patient population. Results: A total of 172 patients and 154 cases were enrolled in the derivation and validation studies, respectively. The revised ABC score consisted of four simple variables: type of clinical specimen (1 to 3 points), Gram-staining result (1 point), presence of local inflammation (2 points), and a systemic inflammatory response (2 points). A revised score of ≥5 points was sensitive (93.8%) and specific (90.6%), and the area under the receiver-operating curve was 0.969 (95% CI
0.957-1). Conclusions: We developed a simple and comprehensive scoring system for diagnosis of nosocomial MRSA infections
this system is applicable in a wide variety of situations.

File： 研究業績書　萩谷 (20180413).docx

DOI： 10.1186/s12879-017-2919-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a leading problem in health care facilities worldwide. Methods: This single-center retrospective cohort study consisted of a derivation phase and a validation phase. The derivation phase included all patients admitted to Osaka University Hospital between May 2010 and April 2011. We proposed a provisional available, bed-sided, comprehensive (ABC) score, and evaluated its accuracy using the clinical diagnosis as a reference. We subsequently revised ABC scores based on k coefficient scores of each variable this revision was validated by applying it to another patient population. Results: A total of 172 patients and 154 cases were enrolled in the derivation and validation studies, respectively. The revised ABC score consisted of four simple variables: type of clinical specimen (1 to 3 points), Gram-staining result (1 point), presence of local inflammation (2 points), and a systemic inflammatory response (2 points). A revised score of ≥5 points was sensitive (93.8%) and specific (90.6%), and the area under the receiver-operating curve was 0.969 (95% CI
0.957-1). Conclusions: We developed a simple and comprehensive scoring system for diagnosis of nosocomial MRSA infections
this system is applicable in a wide variety of situations.

DOI： 10.1186/s12879-017-2919-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

A previously healthy 31-year-old man was referred to us with refractory septic shock accompanied by bilateral conjunctival congestion and erythema of his right lower limb. Nine days after admission, he had bilateral desquamation of the fingertips, and his presentation satisfied the criteria for Kawasaki disease. A serological examination was positive for Yersinia pseudotuberculosis, and he was diagnosed with Far East scarlet-like fever (FESLF). Interestingly, his 11-month-old baby boy had similar symptoms around the same time, indicating the intrafamilial transmission of the pathogen. We should consider FESLF when we encounter a familial occurrence of systemic manifestations of Kawasaki disease.

DOI： 10.2169/internalmedicine.9250-17

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing at medical institutions in Japan without even noticing. Recently, we performed a point prevalence survey for CRE carriage at a medical facility in northern Osaka that demonstrated an unexpectedly high prevalence of blaIMP-6-positive CRE, particularly at long-term care hospitals (LTCH). To identify the risk factors for CRE carriage, we collected clinical data of patients at a representative LTCH. Of 140 patients who were included in this study, 27 (19.3%) were colonized with metallo-beta-lactamase (IMP-6) producers. Pulsed-field gel electrophoresis of the IMP-6 producing Enterobacteriaceae suggested a non-clonal transmission of Escherichia coli, while a clonal spread was shown for Klebsiella pneumoniae. Risk factors for CRE colonization were a longer stay at the hospital stay and a lower independence state, as measured by Norton scales. We propose that a paradigm shift in infection control, inciting a coordinated regional effort to involve LTCHs, should be discussed in the aging society of Japan.

DOI： 10.1016/j.jiac.2018.03.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Verlag Klinisches Labor GmbH  

Background: Procalcitonin (PCT) is a stable biomarker for bacterial infections
however, limited data is available on new trivalent reagents. We evaluated temperature influence on the activity of PCT reagents. Methods: Using both conventional and trivalent reagents, we measured PCT levels of 30 clinical samples, stored residuum at refrigerator (4°C) and room temperature (24°C), and reexamined it after 24 hours. We defined a reduction rate as a percentage of PCT level at 24 hours compared to that after defrost and evaluated a ratio of reduction rate in 4°C to that in 24°C. Results: The reduction rate at room temperature decreased significantly compared to that in the refrigerated condition for all the reagents examined (p &lt
0.001). In addition, the ratio of reduction rate between the conventional and trivalent reagents showed a significant difference (p &lt
0.001) Conclusions: The serum PCT levels significantly decrease at room temperature, particularly when using newer trivalent reagents.

DOI： 10.7754/Clin.Lab.2017.170510

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

Lancefield group G β-hemolytic Streptococcus dysgalactiae subspecies equisimilis (SDSE) has become a leading causative pathogen of invasive streptococcal infection. In this report, we describe a case of disseminated SDSE infection complicated by endogenous endophthalmitis, resulting in panophthalmitis and blindness. A 65-year-old man who underwent mitral valve replacement surgery two months previously was hospitalized due to high fever and right visual loss. A systemic investigation revealed endophthalmitis complicated by mediastinal abscess, prosthetic infective endocarditis, cerebral emboli and hemorrhage, and multiple arthritis. The patient underwent various surgeries, including vitrectomy, mediastinal lavage, mitral valve replacements, joint lavages, as well as an intensive antibiotic treatment. His general condition gradually improved, but the ocular infection developed to panophthalmitis, which ultimately required ophthalmectomy. A literature review regarding Group G-associated endogenous endophthalmitis suggested that the disease occurs in elderly people, is frequently complicated with endocarditis, and yields poor visual prognosis regardless of appropriate antibiotic treatment and surgical therapies. In this aging society, invasive infections with SDSE should be much more recognized among medical practitioners in order to improve patient prognosis.

DOI： 10.1016/j.jiac.2018.04.012

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The number of patients infected with extended-spectrum beta-lactamase (ESBL)-producing organisms has increased dramatically worldwide, and high mortality rates are seen in severely ill patients. This study retrospectively compared the clinical characteristics and outcomes of critically ill patients in an intensive care unit (ICU) at the Tsuyama Chuo Hospital (Okayama, Japan) who were hospitalized for bacteremia caused by ESBL-producing Escherichia coli (ESBL-EC) or non-ESBL-producing E. coli (non-ESBL-EC) between January 2006 and December 2016 (11 years). We analyzed the patients' age, sex, underlying disease(s), sequential organ failure assessment scores, primary focus of bacteremia, empiric antibiotics, rate of appropriateness of empiric antibiotics, and treatment duration, with 28-day mortality being the primary outcome. The study included 24 patients with ESBL-EC bacteremia and 77 with non-ESBL-EC bacteremia. The rate of appropriate initial antibiotic treatment was significantly lower (54.2% vs. 96.1%, respectively
P &lt
0.01) and the mortality due to bacteremia significantly higher (37.5% vs. 15.6%, respectively
P = 0.04) in the ESBL-EC than in the non-ESBL-EC bacteremia group. A subgroup analysis focusing on patients who were administered appropriate empiric antibiotics showed that the 28-day mortality rate did not differ significantly between the two groups (P = 0.23). To our knowledge, this is the first study to compare the outcomes of patients with ESBL-EC and non-ESBL-EC bacteremia in a Japanese ICU setting. Initial empiric antibiotic therapy covering ESBL-producing pathogens should be considered for critically ill patients in the ICU.

DOI： 10.1016/j.jiac.2018.04.016

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Ceftriaxone is a widely used third-generation cephalosporin showing advantageous pharmacokinetic properties and a broad antimicrobial spectrum. We herein report a case of ceftriaxone-induced neurotoxicity in a 56-year-old man on hemodialysis. Seven days after initiating high-dose ceftriaxone, the patient developed impaired consciousness along with facial myoclonus and sporadic phonation. The symptoms clearly disappeared shortly after withdrawal of the drug. Ceftriaxone is considered a safe antibiotic for patients with renal insufficiency, since it is excreted via both haptic and renal pathways. Physicians should note that antibiotic-associated encephalopathy may develop in patients administered ceftriaxone, especially in those complicated with renal dysfunction.

DOI： 10.2169/internalmedicine.8774-16

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO LTD  

Background: The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been reported to be lower in Japan than in many other countries. However, extensive surveillance for CRE carriage has not been performed in Japan.
Aim: To investigate the prevalence of CRE carriage in Japan among convalescent patients considered to be at high risk of being CRE carriers using an improved selective culture medium.
Methods: A cross-sectional survey was conducted in 22 acute care hospitals (ACHs) and 21 long-term care hospitals (LTCHs) in northern Osaka from December 2015 to January 2016. Patients who used incontinence aids, an enteral feeding tube or a urinary catheter were enrolled. Faecal specimens were examined using the newly developed M-ECC for imipenemase (IMP)-producing CRE, which is the most prevalent form of CRE in Japan. The positive isolates were analysed by polymerase chain reaction and sequencing. Risk factors associated with carriage were analysed by logistic regression.
Findings: Among 1507 patients, 184 (12.2%) carried CRE. The percentage of positive patients was significantly higher in LTCHs (14.9%) than in ACHs (3.6%) (P&lt;0.001). Risk factors for CRE carriage were longer hospital stay [odds ratio (OR) 2.59; 95% confidence interval (CI) 1.87-3.60], enteral feeding (OR 3.03, 95% CI 2.08-4.42) and antibiotic exposure (OR 2.00, 95% CI 1.40-2.87). Among the 233 CRE isolates identified, 223 were IMP producers; the remaining isolates did not produce carbapenemase.
Conclusions: This is the first Japanese report to demonstrate the significant spread of CRE in both ACHs and LTCHs using an improved selective medium. A coordinated regional approach may help to prevent further spread. (C) 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jhin.2017.07.015

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Background
Health care workers (HCWs) are frequently exposed to hepatitis B virus (HBV) infection. The efficacy and safety of immunization with the hepatitis B (HB) vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.
Methods
This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs) titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years), and long responders (those who retained positive anti-HBs levels for 3 years and more). We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.
Results
From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229), 54.5% after two doses (n = 11), and 4.2% after a single dose (n = 24). Of 213 primary responders, the anti-HBs levels of 95 participants (44.6%) fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.
Conclusion
Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective, large-scale study is warranted to support our findings.

DOI： 10.1371/journal.pone.0187661

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DOI： 10.1002/jgf2.71

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The bacterial enzyme New Delhi metallo-beta-lactamase hydrolyzes almost all beta-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-beta-lactamase gene, bla(NDM), poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring bla(NDM) genes were identified from these isolates. Multiple bla(NDM) genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C-2 plasmid harboring bla(NDM-1) (n = 1), IncX3 plasmids harboring bla(NDM-4) (n = 2) or bla(NDM-7) (n = 1), IncFII plasmids harboring bla(NDM-4) (n = 1) or bla(NDM-5) (n = 3), and a multireplicon F plasmid harboring bla(NDM-5) (n = 1). Comparative analysis highlighted the diversity of the bla(NDM)-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring bla(NDM) genes in the hospital.

DOI： 10.1371/journal.pone.0184720

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We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M.hominis infections are prone to being misdiagnosed and undertreated. M.hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail.

DOI： 10.1111/tid.12697

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A PCR-dipstick chromatography technique was designed and evaluated for differential identification of blaNDM, blaKPC, blaIMP, and blaOXA-48 carbapenemase genes directly in stool specimens within 2 h. It is a DNA-DNA hybridization-based detection system where PCR products can be easily interpreted by visual observation without electrophoresis. The PCR-dipstick showed high sensitivity (93.3%) and specificity (99.1%) in directly detecting carbapenemase genes in stool specimens compared with multiplex PCR for genomic DNA of the isolates from those stool specimens.

DOI： 10.1128/AAC.00067-17

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Propionibacterium acnes is increasingly known as a causative organism for post-neurosurgical infection; however, no clinical studies have examined the risk factors associated with P. acnes infections. Clinical data obtained from 14 cases of P. acnes infection and 28 controls infected with other pathogens were analyzed. Craniotomy, malignancy, and prolonged duration of operation were significantly associated with the onset of P. acnes infection. No fatal cases were reported. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.10.003

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Identifying transmission route of antimicrobial-resistant pathogen is essential for appropriate infection control strategy in healthcare facilities. We report the utility of single-nucleotide variation analysis in tracing nosocomial transmission of antimicrobial-resistant pathogens by describing a pseudo-outbreak case of carbapenem-resistant Klebsiella pneumoniae. The present case highlights that infection control strategy should encompass pathological dissection rooms, neglected but potentially highly contaminated places in hospitals.

DOI： 10.1007/s15010-017-0986-3

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We retrospectively analyzed the cases of 14 patients (9 women, 5 men, mean age: 51.6 years) with cytomegalovirus (CMV) involvement in the esophagus, stomach, and/or duodenum diagnosed at a single center, to determine their endoscopic features and clinical backgrounds. Thirteen patients (92.9%) had hematologic disease; the other had rheumatoid arthritis. Of the former, 12 patients underwent allogeneic hematopoietic stem cell transplantation, and 9 of these patients had graft-versus-host disease (GVHD) before undergoing esophagogastroduodenoscopy (EGD). All 14 patients had been taking one or more immunosuppressive agents including cyclosporine (n=10), corticosteroids (n= 9), mycophenolic acid (n= 6), tacrolimus (n=3), and methotrexate (n=1). Tests for CMV antigenemia were positive in 11 patients (78.6%). EGD examinations revealed esophageal (n=3), gastric (n=9), and duodenal involvement (n=6). Macroscopically, esophageal lesions by CMV infection presented as redness (n=1), erosions (n=1), and ulcers (n=1). Gastric lesions manifested as redness (n=7), erosions (n=3), exfoliated mucosa (n=2), and verrucous erosions (n=1). Mucosal appearances in the duodenum varied: redness (n=2), ulcers (n=2), multiple erosions (n=2), single erosion (n=1), edema (n=1). CMV was detected even in the intact duodenal mucosa (n=1). In conclusion, physicians must recall the relevance of CMV infection when any mucosal alterations exist in the upper gastrointestinal tract of immunosuppressed patients.

DOI： 10.18926/AMO/54977

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Background: Identification of carbapenemase-producing Enterobacteriaceae (CPE) in faecal specimens is challenging. This fact is particularly critical because low-level carbapenem-resistant organisms such as IMP-producing CPE are most prevalent in Japan. We developed a modified selective medium more suitable for IMP-type CPE.
Methods: Fifteen reference CPE strains producing different types of beta-lactamases were used to evaluate the commercially available CHROMagar KPC and chromID CARBA as well as the newly prepared MC-ECC medium (CHROMagar ECC supplemented with meropenem, cloxacillin, and ZnSO4) and M-ECC medium ( CHROMagar ECC supplemented with meropenem and ZnSO4). A total of 1035 clinical samples were then examined to detect CPE using chromID CARBA and M-ECC medium.
Results: All tested strains producing NDM-,KPC-, and OXA-48-carbapenemases were successfully cultured in the media employed. Although most of the IMP-positive strains did not grow in CHROMagar KPC, chromID CARBA, or MC-ECC, all tested strains grew on M-ECC. When faecal samples were applied to the media, M-ECC medium allowed the best growth of IMP-type CPE with a significantly higher sensitivity (99.3%) than that of chromID CARBA (13.9%).
Conclusions: M-ECC medium was determined as the most favourable selective medium for the detection of IMP-type CPE as well as other types of CPE.

DOI： 10.1186/s12879-017-2312-1

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DOI： 10.1097/MPA.0000000000000708

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Clostridium difficile generally causes enterocolitis by producing pathogenic toxins, while extraintestinal infections with C. difficile are extremely rare. Here we report the first documented case of an infective thoracic aortic aneurysm caused by nontoxic C. difficile that occurred after vascular interventions including endovascular aortic repair. The present case illustrates that endovascular interventions may expose patients to the rare infection by yielding the ischemic intestinal tract as an entry site for the pathogen into the bloodstream and providing an anaerobic environment inside the thrombosed aneurysm. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.08.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Society for Microbiology  

Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.

DOI： 10.1128/genomeA.00852-17.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Society for Microbiology  

Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.

DOI： 10.1128/genomeA.00852-17.

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A 77-year-old female with renal dysfunction, hypercalcemia, and hypercalciuria was presented. Systemic investigations including renal biopsy showed that the patient had Fanconi syndrome secondary to renal sarcoidosis. Treatment with 25 mg per day of prednisolone was initiated and her condition improved. Complication of Fanconi syndrome in patients with sarcoidosis is extremely rare. Although the pathological mechanism is still unknown, corticosteroid therapy was effective for ameliorating proteinuria, glycosuria, hypercalciuria, and aminoaciduria.

DOI： 10.3109/14397595.2014.1002163

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Insulinoma is a rare, usually benign, pancreatic neuroendocrine tumor. The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease. We herein report a patient with insulinoma who manifested paroxysmal hypertension and neuroglycopenic symptoms. The possible etiology of hypertension induced by an insulinoma is catecholamine release in response to hypoglycemia, which may cause acute hypertension through activation of the sympatho-adrenal system. This case implies that sustained hyperinsulinemia due to insulinoma can be functionally linked to the induction of paroxysmal hypertension.

DOI： 10.2169/internalmedicine.56.7758

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We herein report the first documented case of acute hypersensitivity pneumonitis in which Candida guilliermondii was the possible causative organism. A young Japanese woman presented to our hospital with relapsing respiratory symptoms accompanied by high fever. A detailed interview revealed that the onset of the symptoms occurred shortly after using a humidifier in her home. Her symptoms showed spontaneous improvement soon after admission, and an examination of her bronchoalveolar lavage fluid revealed the specific infiltration of inflammatory cells, which predominantly consisted of lymphocytes. Precipitin testing showed a positive reaction to C. guilliermondii, which was isolated from the home humidifier. Repeated history taking is essential for diagnosing occult respiratory disorders.

DOI： 10.2169/internalmedicine.9055-17

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DOI： 10.2169/internalmedicine.56.8403

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Objective Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes fatal infections in critically ill or immunocompromised patients. S. maltophilia bacteremia (SMB) is a rare condition, and its clinical characteristics in Japanese settings are not well known.
Methods The medical charts of patients with SMB were retrospectively reviewed at two medical facilities (Okayama University Hospital and Tsuyama Chuo Hospital) for seven years. The data were analyzed along with those previously reported from other Japanese facilities.
Result A total of 181 patients (110 men and 71 women) were evaluated. The major underlying diseases included hematologic malignancy (36.5%), solid organ malignancy (25.4%), and neutropenia (31.5%). The recent use of carbapenem was seen in 56.9% of the cases in total, and more than one-third of the patients in our hospitals were treated with carbapenem at the onset of SMB. Of 28 (63.6%) of 44 cases treated for S. maltophilia, those who did not survive were more likely to have been treated with broad-spectrum antibiotics. A multivariate analysis revealed that a higher updated Charlson Comorbidity Index [odds ratio (95% confidence interval), 1.75 (1.11-2.75); p=0.015] and intubation [odds ratio (95% confidence interval), 12.6 (1.62-97.9); p=0.016] were associated with mortality in our cases. Pathogens were often resistant to ceftazidime but susceptible to minocycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. The overall mortality rates within 30 and 90 days were 37.5% and 62.5%, respectively.
Conclusion The clinical characteristics of SMB in Japanese cases were similar to those reported from other countries. Clinicians should be aware that breakthrough infection by S. maltophilia may occur during administration of carbapenem.

DOI： 10.2169/internalmedicine.56.6141

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Background: There is no current way to determine the actual blood and body fluid exposure (BBFE) incidence in hospitals. We propose a simple, reliable, and widely available method for the accurate estimation of BBFE.
Methods: Data for BBFE for healthcare workers between 2006 and 2015 at Osaka University Hospital were retrospectively extracted from the electronic records. Annual positivity of hepatitis C virus (HCV) antibody in the source individuals and overall patient population were calculated over time. We created an estimation formula focusing on the difference in HCV positivity between the source individuals and overall patient population for the actual number of BBFEs. A linear regression model was used to evaluate the temporal change in the reported and estimated BBFEs.
Results: During the study period, 937 BBFEs were reported. HCV positivity between the post-BBFE cohort and overall patient population greatly differed; the incidence ratio ranged from 2.1 to 5.7. The linear regression model revealed that the reported BBFEs did not significantly change during the study period (the slope, 1.315 [95% confidence interval (C.I.): -0.849 to 3.480, p = 0.199]). The annual incidence ratio of the estimated and reported BBFEs significantly reduced over time (the slope, -0.287 [95% C.I.: -0.488 to -0.086, p = 0.011]), indicating that, although the reported number of BBFEs seemed unchanged, the estimated incidence decreased.
Conclusions: We propose a novel and simple approach to estimating the actual incidence of BBFEs in hospitals using the difference in HCV positivity between the post-BBFE cohort and overall patient population.

DOI： 10.7754/Clin.Lab.2017.170340

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Development of treatment with immunomodulatory agents has improved prognosis of various autoimmune-related diseases. A sphingosin-1-phosphate receptor modulator, or fingolimod, is the first licensed oral drug for relapsing-remitting multiple sclerosis. The agent reduces circulating lymphocytes by trapping T cells in lymph nodes, possibly leading to reactivation of latent viruses. A 41-year-old Japanese woman who had been treated with fingolimod for 2 years presented with unilateral sore throat. Laryngoscopy revealed exudates unilaterally emerging on the left side of her supraglottic region. Serum level of the varicella zoster virus (VZV)-specific IgG was markedly elevated, and a result of genome sequence using the exudates demonstrated VZV as a possible causative pathogen. Fingolimod therapy was discontinued and the patient was successfully treated with intravenous acyclovir. This is the first reported case of fingolimod-associated herpes zoster laryngitis, in which the local VZV reactivation was demonstrated by next-generation sequencing technology. The present case highlights that the occurrence of VZV reactivation should be recalled in any patients undergoing fingolimod therapy. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.07.011

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Kikuchi-Fujimoto disease (KFD) is a benign cause of self-limiting subacute necrotizing lymphadenitis. KFD is rarely complicated with reactive hemophagocytic lymphohistiocytosis (HLH), and the clinical features of the simultaneous occurrence of these conditions are uncertain. A 30-year-old Japanese man with a persistent fever and sore throat presented to our hospital for treatment. Laboratory analysis showed bicytopenia, and radiological studies showed systemic lymphadenopathy accompanied by splenomegaly. A bone marrow examination showed hemophagocytic macrophages, suggesting HLH. Malignant lymphoma was suspected as a possible underlying disease, but the histology of the lymph nodes led to a final diagnosis of KFD and treatment with prednisolone (1 mg/kg/day), resulting in clinical improvement. This case highlighted the importance and difficulty of differentiating KFD from malignant lymphoma as an underlying condition of HLH. The literature review showed that patients with HLH-associated KFD may have higher serum ferritin and lactate dehydrogenase levels compared to typical KFD cases. Definite diagnosis based on pathological examination is essential for a better understanding of this rare disease. The presence of systemic lymphadenopathy does not exclude the possibility of KFD. This case serves to remind physicians that KFD is a potential etiology of HLH.

DOI： 10.18926/AMO/54597

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Background: With the development of invasive medical procedures, an increasing number of healthcare-associated infective endocarditis cases have been reported. In particular, non-nosocomial healthcare-associated infective endocarditis in outpatients with recent medical intervention has been increasingly identified.
Case presentation: A 66-year-old man with diabetes mellitus and a recent history of intermittent urethral self-catheterization was admitted due to a high fever. Repeated blood cultures identified Pseudomonas aeruginosa, and transesophageal echocardiography uncovered a new-onset severe aortic regurgitation along with a vegetative valvular structure. The patient underwent emergency aortic valve replacement surgery and was successfully treated with 6 weeks of high-dose meropenem and tobramycin. Historically, most cases of P. aeruginosa endocarditis have occurred in the right side of the heart and in outpatients with a history of intravenous drug abuse. In the case presented, the repeated manipulations of the urethra may have triggered the infection. Our literature review for left-sided P. aeruginosa endocarditis showed that non-nosocomial infection accounted for nearly half of the cases and resulted in fatal outcomes as often as nosocomial cases. A combination therapy with anti-pseudomonal beta-lactams or carbapenems and aminoglycosides may be the preferable treatment. Medical treatment alone may be effective, and surgical treatment should be carefully considered.
Conclusions: We presented a rare case of native aortic valve endocarditis caused by P. aeruginosa. This case illustrates the importance of identifying the causative pathogen(s), especially for outpatients with a recent history of medical procedures.

DOI： 10.1186/s12879-016-1757-y

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A 64-year-old man with advanced liver cirrhosis was transferred to an emergency center due to septic shock and markedly inflamed left leg. Under a clinical diagnosis of necrotizing soft tissue infection (NSTI), the patient undertook intensive therapy but died 25 h after arrival. The pathogenic organism, Serratia marcescens, was later isolated from blood and soft tissue cultures. NSTI is very rarely associated with S. marcescens. A literature review showed that only 16 such cases, including our case, have been reported to date. Our case is the first evidence of an S. marcescens NSTI in a patient with liver cirrhosis. S. marcescens NSTI has an extremely high mortality rate; total mortality and mortality in cases involving the extremities were 75% (12 of 16 cases) and 83.3% (10 of 12 cases), respectively. Physicians need to be aware that S. marcescens can induce fatal infections in community patients. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2015.11.013

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Gram-negative fusiform rods were detected in a blood culture obtained from a 63-year-old man who had been hospitalized for a long duration for severe heart failure. Although the organism could not be identified using a conventional method, it was finally identified as a bacterium of the Capnocytophaga ochracea group based on the results of biochemical testing, 16S rRNA sequencing and a matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Although neutropenic patients with poor oral hygiene are exclusively vulnerable to Capnocytophaga bacteremia, this case was unique because such predisposing conditions were not noted. A multi-centered investigation is warranted for a better understanding of this clinically rare, but potentially pathogenic organism.

DOI： 10.2169/internalmedicine.55.6593

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A 68-year-old man with persistent bacteremia accompanying a large iliopsoas abscess, vertebral osteomyelitis, discitis and central venous port infection caused by methicillin-resistant Staphylococcus aureus (MRSA) was admitted to our hospital. During the course of treatment, the emergence of a daptomycin (DAP)-resistant MRSA strain was confirmed; the minimum inhibitory concentration was 1 to 2 mu g/mL for vancomycin and more than 1 mu g/mL for DAP. Although the bacterial cell wall was not significantly thickened, an increased positive surface charge and single-nucleotide polymorphism within mprF have been confirmed in DAP-resistant strains. Still rare, but clinicians need to be cautious of the emergence of DAP-resistant MRSA during treatment.

DOI： 10.2169/internalmedicine.55.4763

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DOI： 10.2169/internalmedicine.55.5347

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A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus ( HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated.

DOI： 10.2169/internalmedicine.55.6287

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DOI： 10.2169/internalmedicine.55.6490

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DOI： 10.2169/internalmedicine.55.6574

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER HEIDELBERG  

DOI： 10.1007/s15010-015-0804-8

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We report a 42-year-old female who initially complained of sub-acute onset of right upper quadrant abdominal pain with right shoulder pain. A CT scan incidentally revealed an adrenal tumor, and a final diagnosis of pheochromocytoma was made on the basis of endocrinological examinations. Symptomatically, the pheochromocytoma in our patient mimicked a hepato-biliary disease by presenting abdominal pain accompanying right shoulder pain that was assumed to be referred pain via the right phrenic nerve. Physicians may need to consider the possibility of pheochromocytoma in patients with abdominal symptoms.

DOI： 10.14442/jgfm.16.4_292

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Global spread and evolutionary links of an epidemic Clostridium difficile strain (PCR-ribotype 027) have been noted in recent decades. However, in Japan, no outbreaks caused by type 027 have been reported to date. A total of 120 C. difficile isolates from patients at 15 hospitals during non-outbreak seasons between 2011 and 2013 as well as 18 and 21 isolates collected from two hospitals in 2010 and 2009, respectively, in outbreak periods in Japan, were examined. Among these 120 isolates, Japan-ribotypes smz and ysmz (subtype variant of smz) were the most predominant (39.2 %) followed by Japan-ribotype trf (15.8 %). Types smz/ysmz and trf were also concurrently predominant at two hospitals in the outbreak settings. Out of the five binary toxin-positive isolates observed, only one was PCR-ribotype 027 and another PCR-ribotype 078. Type smz was later found to correspond to PCR-ribotype 018. High rates of resistance against gatifloxacin, moxifloxacin, erythromycin and clindamycin were observed in the PCR-ribotype 018 isolates. Interestingly, all trf isolates were toxin A-negative, toxin B-positive, but they did not correspond to PCR-ribotype 017, thus being assigned a new ribotype (PCR-ribotype 369). In conclusion, PCR-ribotypes 018 (smz) and 369 (trf) were identified as major circulating strains in both outbreak and non-outbreak settings in Japan. Given their epidemiological relevance, molecular investigations are warranted to clarify potential evolutionary links with related strains found elsewhere, such as PCR-ribotypes 018 and 017 from Europe and North America.

DOI： 10.1099/jmm.0.000149

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A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion; however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features.

DOI： 10.18926/AMO/53679

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：PHARMACEUTICAL SOC JAPAN  

Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

DOI： 10.1248/yakushi.15-00003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MANEY PUBLISHING  

DOI： 10.1179/1973947814Y.0000000196

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Eosinophillic glanuromatosis with polyangitis (EGPA) usually occurs in patients with a recent history (usually less than 10 years) of uncontrolled bronchial asthma. Here we describe a case of EGPA that occurred in a 68-year-old female who had well-controlled bronchial asthma for 17 years. A leukotriene receptor antagonist that had been prescribed one week before onset might have triggered the disease. Our case shows that there is a wide spectrum of clinical characteristics of EGPA, making diagnosis difficult in a primary care setting.

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DOI： 10.1016/j.bjid.2015.01.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

An 81-year-old Japanese male with primary Sjogren syndrome (pSS) developed a low-grade fever and productive cough which were refractory to antibiotic therapy. Based on the high level of eosinophils observed in his bronchial alveolar lavage, he was diagnosed with chronic eosinophilic pneumonia (CEP) and successfully treated by oral prednisolone. Interstitial lung diseases associated with pSS (pSS-ILDs) usually present as nonspecific interstitial pneumonia or usual interstitial pneumonia; therefore, the present case is extremely unique in that the patient's condition was complicated with CEP. A diagnosis of advanced gallbladder cancer was made in the patient's clinical course, suggesting the advisability of a whole-body workup in cases of pSS, especially in elderly patients.

DOI： 10.18926/AMO/53342

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We report the case of a 46-year-old hypertensive Japanese female with renal insufficiency related to unilateral renal hypoplasia. The patient was found to have developed paraganglioma in the retroperitoneal space over a 5-year period. Catecholamine-producing tumors are not usually recognized as conditions associated with renal hypoplasia. Our long-term observation of the patient eventually led us to the diagnosis of paraganglioma. In hypertensive patients with chronic kidney disease, not only the renin-angiotensin-aldosterone system but also catecholamine activity may be involved, particularly in the patients whose cases are complicated with unilateral renal hypoplasia.

DOI： 10.18926/AMO/53341

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Language：English   Publisher：MANEY PUBLISHING  

DOI： 10.1179/1973947814Y.0000000215

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Case: A 74-year-old woman with a week-long history of cold symptoms was diagnosed with Lemierre syndrome that involved her left external jugular vein. Outcome: The patient was successfully treated with 4 weeks of antibiotics and anticoagulant treatment. Typical cases of Lemierre syndrome involve only the internal jugular vein. The external jugular vein is anatomically distant from the pharyngolaryngeal space and usually does not receive blood or lymphatic flow from there. Thus, Lemierre syndrome ordinarily does not involve the external jugular vein and clinical characteristics of external jugular vein-involving Lemierre syndrome have not been uncovered, mainly due to its rarity. Based on our review, it would not much differ from those of typical cases. Conclusion: Considering the potential severity and mortality, more attention should be paid to this potentially fatal disease that may demonstrate atypical manifestation, as shown in this case. Accumulation of cases would be needed for further understanding.

DOI： 10.1002/ams2.61

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

We herein present a rare case of Actinomyces turicensis bacteremia that was caused by pyometra. The patient was successfully treated with transvaginal drainage and antibiotic therapy. A literature review in MEDLINE showed that there have been only 8 previously reported cases of A. turicensis bacteremia. This infection frequently occurs in patients with visceral abscesses, and blood culture examinations usually reveal a polymicrobial pattern. However, the prognosis of such patients has been reported to generally be benign. Due to difficulties in performing bacterial identification and the wide-spectrum clinical pictures associated with this bacteremia, no comprehensive understanding of the clinical features of each Actinomyces species has yet been established.

DOI： 10.2169/internalmedicine.54.4637

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DOVE MEDICAL PRESS LTD  

Objectives: Stenotrophomonas maltophilia shows wide-spectrum resistance to antimicrobials and causes various infections in immunocompromised or critically ill patients with high mortality. In this era of antibiotics resistance, a revival of old antibiotics is now featured. We examined the clinical usefulness of latamoxef (LMOX) for the treatment of S. maltophilia infection. Patients and methods: The observational study was retrospectively performed at Okayama University Hospital (Okayama, Japan) from January 2011 to December 2013. LMOX was administered to 12 patients with S. maltophilia infection, with eleven of those patients being admitted to the intensive care unit. Results: Underlying conditions of the patients included postoperation, hematological transplantation, hepatic transplantation, and burn. Major infectious foci were surgical site infection (six cases), respiratory infection (four cases), blood stream infection (three cases), and burn site infection (one case). The doses of LMOX administered ranged from 1 g/d to 3g d for ten adult patients and from 40 mg/kg/ d to 80 mg/kg/d for two pediatric patients. Microbiologic failure was seen in five (41.7%) of 12 cases, and 30-day and hospital mortality rates were 25% and 50%, respectively. Minimum inhibitory concentrations of LMOX were higher in the deceased group (4-64 mu g/mL) than in the surviving group (1-4 mu g/ mL). Conclusion: LMOX treatment is not recommended for the treatment of S. maltophilia infection. Further investigation would be needed before its clinical use.

DOI： 10.2147/IDR.S90726

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A 34-year-old man with 22q11.2 deletion syndrome (DiGeorge syndrome) concurrently suffered from myopathy and eosinophilic pneumonia shortly after receiving daptomycin (DAP) for right-sided infective endocarditis. The simultaneous occurrence of these phenomena in relation to DAP therapy has not been previously well described. An allergic reaction was suspected as a possible etiology of these DAP-related complications. This case highlights the need for close observation in order to detect both musculoskeletal and respiratory disorders from the start of DAP therapy. Physicians should pay more attention to this new drug, which is expected to be frequently used in various clinical settings.

DOI： 10.2169/internalmedicine.54.3397

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We herein report a case of Klebsiella oxytoca-producing IMP-1 that was detected as a first isolate of carbapenem-resistant Enterobacteriaceae (CRE) at our facility. Since K. oxytoca is an uncommon strain for CRE, we speculated that the resistant organism had already spread out inside the hospital. Metallo-beta-lactamases promotes antibiotic resistance in Enterobacteriaceae, which potentially yields problematic issues in clinical settings. Active surveillance of antibiotic resistant strains is important and should be repeatedly highlighted. Furthermore, appropriate methods should be established to detect highly resistant strains.

DOI： 10.2169/internalmedicine.54.4965

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We report a case of nephrostomy-associated urinary tract infection caused by Elizabethkingia meningoseptica that occurred in a patient with retroperitoneal fibrosis. Though conventional identification methods failed to detect the causative organism, it was identified on the basis of the complete sequencing of 16S rRNA. Four weeks of levofloxacin and minocycline administration successfully eradicated the infection. E. meningoseptica rarely causes urinary tract infections, and we believe that this is the first such case in which the isolate was genetically confirmed. The accurate identification of the organism is necessary for the provision of appropriate treatment and to obtain a better understanding of its epidemiology and pathogenicity.

DOI： 10.2169/internalmedicine.54.4998

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.54.3392

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.54.4134

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.54.4262

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.54.3752

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.54.4404

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A 67-year-old man with a persistent high fever was diagnosed to have an infective aneurysm in his left internal iliac artery. A blood culture detected a gram-negative spiral rod that was first identified as Campylobacter fetus subsp. venerealis based on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. However, the strain was finally confirmed to be Campylobacter fetus subsp. fetus based on a genetic analysis. The infection was successfully treated with emergency resection of the aneurysm, followed by 4 weeks of antibiotic therapy. Involvement of the peripheral artery is uncommon in cases of C. fetus-infective aneurysm. To figure out the epidemiology and pathogenicity of C. fetus infection, the accurate identification of the responsible organisms is essential.

DOI： 10.2169/internalmedicine.54.4845

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We herein describe the first reported case of pyogenic spondylitis and diskitis caused by Helicobacter cinaedi. The results of magnetic resonance imaging and the histology of biopsied tissue were suggestive of acute infection at the lumbar spine. The pathogen was obtained by a blood culture examination and identified by 16S rRNA analysis. Eight weeks of antibiotics therapy resulted in a good clinical course. H. cinaedi infections have been increasingly reported in recent years, but the pathogen's epidemiological and pathological characteristics are still unclear. One of the difficulties in understanding the pathogenesis of H. cinaedi has been the challenges in cultivating the pathogen. Novel strategies for the diagnosis of H. cinaedi must be developed.

DOI： 10.2169/internalmedicine.54.4726

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We herein report a heterosexual Japanese man in his forties who had been suffering from advanced dementia and personality change for 4 years. Positive results of a serological test for syphilis, Treponema pallidum hemagglutination assay, and fluorescent treponemal antibody-absorption test of both serum and cerebral spinal fluid led to the diagnosis of neurosyphilis. Jarisch-Herxheimer reaction was seen shortly after the first dose of penicillin was administered to the patient. His cognitive function did not recover after treatment. The incidence of syphilis has been reported to be increasing. Neurosyphilis should not be overlooked as an etiology for progressive dementia even in this post-antibiotic era.

DOI： 10.2169/internalmedicine.54.4956

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ Publishing Group  

DOI： 10.1136/bcr-2014-207572

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

A 53-year-old man with a past medical history of total arch replacement surgery and severe aortic regurgitation presented with a 1-month history of persistent general malaise, anorexia, body weight loss and night sweats. His recent history included gingival hyperplasia for 6 years, gingivitis after tooth extraction 3 years before, prolonged inflammatory status for 4 months, fundal hemorrhage and leg tenderness for 2 months. A pathogen was detected from blood culture, but conventional microbiological examination failed to identify the pathogen. The organism was eventually identified as Cardiobacterium valvarum by 16S rRNA analysis, and the patient was diagnosed with infective endocarditis and prosthetic vascular graft infection. The patient received intravenous antibiotic therapy using a combination of ceftriaxone and levofloxacin for 5 weeks and was discharged with a good clinical course.
C. valvarum is a rare human pathogen in clinical settings. Only 10 cases have been reported to date worldwide, and therefore, the clinical characteristics of C. valvarum infection are not fully known. This is a first well-described case of C. valvarum infection in Japan, and further, a first report of aortic prosthetic vascular graft infection worldwide. Identification of C. valvarum is usually difficult due to its phenotypic characteristics, and molecular approaches would be required for both clinicians and microbiologists to facilitate more reliable diagnosis and uncover its clinical picture more clearly. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2014.07.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Campylobacter spp. usually cause gastrointestinal infections, but among them, Campylobacter fetus is a well-known organism causing mycotic abdominal aortic aneurysm (MAAA), which requires proper surgical intervention and antibiotic therapy. We report a 65-year-old man who was successfully treated by an in situ operation using a rifampicin (RFP) ebonded J-Graft for C. fetus-induced MAAA. We performed a review of the English literature on MAAA caused by C. fetus and summarized the results of the cases (28 cases). All but 2 of the patients (92.9%) were men. Blood culture and arterial wall culture were positive in 63% and 73.1% of the cases, respectively. Aneurysm rupture was seen in half of the patients, and approximately half of those patients died. Among the 18 patients who underwent in situ graft replacement, only 1 patient (5.6%) died after surgery. Antibiotic therapy was performed for more than 1 month in most cases, and overall mortality rate was 25.9% (7 of 27 cases, 3 deaths before the operation and 4 deaths after surgery). Although extra-anatomic bypass has been conventionally performed after complete resection of an MAAA, the utility of in situ surgery has generally been recognized. Our review suggests that the in situ operation can be a choice also in cases of C. fetus-associated MAAA. Furthermore, our case suggested the clinical utility of a newly manufactured prosthetic graft, J-Graft, for such surgical treatment.

DOI： 10.1016/j.avsg.2014.06.072

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Language：English   Publisher：CONTEXTO  

DOI： 10.1016/j.bjid.2014.06.0061413

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

The laboratory diagnostic methods for Clostridium difficile infection (CDI) include toxigenic culture, enzyme immunoassays (EIAs) to detect the toxins of C. difficile, and nucleic acid amplification tests (NAATs) to detect C. difficile toxin genes, but each of these methods has disadvantages; toxigenic cultures require a long time to produce results, EIAs have low sensitivity, and NAATs that target DNA cannot distinguish vegetative cells from spores and dead cells. Here we report a new detection method that uses reverse transcription polymerase chain reaction to target the toxin-gene transcripts. This method was able to specifically detect the vegetative cells of toxigenic C. difficile in fecal samples in spike tests, with a minimum detection limit of 5x10(2) colony-forming units per 100mg of stool specimen. The performance of this method was also demonstrated in a pilot scale evaluation using clinical fecal specimens, which showed that this method may be more sensitive than EIA and requires a shorter time than toxigenic culture. This method could potentially be applied in the clinical laboratory to detect C. difficile in fecal specimens. The ability of this method to discriminate the presence of vegetative cells from spores and dead cells could help to further the understanding of CDI.

DOI： 10.1111/1348-0421.12189

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Aim: Extended-spectrum beta-lactamases and AmpC beta-lactamases give resistance to Enterobacteriaceae against cephalosporins, which are important drugs in various clinical settings. Within 5 days, a total of eight strains of Citrobacter freundii and two strains of Escherichia coli, all of which were resistant to third-generation cephalosporins, were isolated from six different patients in a critical care center. We carried out epidemiological and genetic studies to confirm the situation to be an outbreak by a single strain or a beta-lactamase-producing gene. Methods: A review of patients' clinical data, pulsed-field gel electrophoresis epidemiological study against the strains, and polymerase chain reaction analysis for the detection of extended-spectrum beta-lactamase genes (TEM, SHV, CTX-M-1, CTX-M-2, and CTX-M-9) and multiplex polymerase chain reaction analysis for plasmid-mediated AmpC-beta-lactamase genes were carried out. Results: Pulsed-field gel electrophoresis showed none of the subjects were genetically identical organisms. However, all strains possessed either extended-spectrum beta-lactamases (TEM, CTX-M-2, and CTX-M-9) or AmpC-beta-lactamases. One patient carried both extended-spectrum beta-lactamase- and AmpC- beta-lactamase-producing organisms. Conclusion: This study revealed that various types of easily transmittable drug resistance genes exist in the critical care setting concurrently. This case was not an outbreak of such strains, but the present situation might indicate a more serious condition than a mere outbreak of a single resistant strain. Enterobacteriaceae that possess extended-spectrum beta-lactamases or AmpC-beta-lactamases are increasingly common in many medical institutions in Japan, and constitutive monitoring of drug-resistant organisms and proper contact precautions are essential to prevent possible outbreaks.

DOI： 10.1002/ams2.64

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DOI： 10.1002/ams2.40

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Raoultella ornithinolytica is a rare pathogen in human infection and bacteremic cases had been scarcely reported. For further comprehension of the rare infection, we summarized clinical characteristics of 6 cases that were detected at our medical facility and 5 cases from previous literature. The most common infectious focus was biliary infection and elderly patients with a history of any biliary intervention or malignancy were considered to be at a great risk for the infection. The prognosis of the patients was quite satisfactory. Bacterial identification in this report was performed on the basis of biochemical tests alone, and further investigations by molecular analysis are required to confirm our findings. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2014.05.005

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A 79-year-old man who had undergone a right femoropopliteal (FP) bypass operation 6 weeks previously was diagnosed with vascular graft infection caused by Staphylococcus lugdunensis. Another FP bypass operation was performed, with long-term administration of antibiotics, and the patient eventually recovered well without any recurrences for over 2 years. Although S. lugdunens is classified as coagulase-negative Staphylococcus, its pathogenicity has been reported to be equal to that of S. aureus. Based on the literature review, the organism characteristically colonizes the inguinal area of human skin; thus, operations such as FP bypass grafting may place patients at a relatively high risk for infection by S. lugdunensis, a potentially high-pathogenicity organism.

DOI： 10.18926/AMO/52658

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

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The effect of antibiotics during the perioperative period of percutaneous dilatational tracheostomy (PDT) is still controversial. A total of 297 patients who underwent the PDT procedure were divided into 2 groups: those administered antibiotics perioperatively and those not administered antibiotics. Wound infections were noted in 7 cases (incidence rate, 2.36%) and no death was recorded. Of the 69 patients without antibiotics, 5 developed wound infections (incidence rate, 7.25%), while only 2 of the 228 patients with antibiotics developed wound infections (incidence rate, 0.88%) (p = 0.002; risk ratio, 8.82; 95% confidence interval, 1.67-46.6). Of the 7 cases of wound infection, 5 cases occurred during the early period after PDT (within 7 days). Collectively, the present results suggest that prophylactic administration of antibiotics may prevent the incidence of PDT-induced wound infection, especially in the early phase after the PDT procedures. The need for antibiotics in PDT should be reconsidered.

DOI： 10.18926/AMO/52402

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Chromobacterium violaceum is sensitive to temperature and the infection is usually confined to tropical or subtropical regions. Since Japan has a warm climate, C. violaceum has been scarcely isolated from clinical specimens. With global warming, however, the geographical distribution of C violaceum infection is likely to change. We report two cases of C violaceum nosocomial pneumonia that occurred at an intensive care center in Japan. C violaceum was first detected from a patient in the same center as a pathogenic organism of pneumonia. Later, the organism was isolated from sputum and a ventilator circuit tube of another patient in the center. The two patients were admitted to the center in nearby beds for several days. All of the pathogens were confirmed to be C violaceum by the nucleic acid sequence of the 16S rRNA gene and were proven to be genetically identical organisms by pulsed field gel electrophoresis. Both patients were managed with well-humidified and heated oxygen using a venturi mask and ventilator to promote excretion of sputum. It was thought that the medical respiratory care devices that provide a humid and warm environment, an optimal condition for proliferation of C violaceum, can contribute to C violaceum infection in a hospital environment. (C) 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2013.10.001

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DOI： 10.1089/bfm.2013.0057

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DOI： 10.2169/internalmedicine.53.1777

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We herein report a case of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that was successfully treated with combination therapy consisting of high-dose daptomycin (DAP, 10 mg/kg) and rifampicin. The patient's condition was complicated with multiple infectious foci, including an iliopsoas abscess and epidural abscess, as well as discitis and spondylitis at the cervical, thoracic and lumbar levels. Monotherapy treatments with vancomycin, linezolid and usual-dose DAP were all ineffective. It has been shown that usual-dose DAP administration may result in the emergence of a resistant strain and treatment failure. We would like to emphasize the importance of high-dose DAP therapy for MRSA bacteremia, a condition with a potentially high mortality rate.

DOI： 10.2169/internalmedicine.53.2711

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DOI： 10.2169/internalmedicine.53.3377

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A 69-year-old man with diabetes mellitus was diagnosed with a prostate abscess. Although the pathogen was fluoroquinolone-resistant Escherichia coli and the oral administration of trimethoprim-sulfamethoxazole was initiated, the infection recurred after three months. The antibiotic therapy was subsequently changed to intravenous fosfomycin, and the patient's condition promptly improved. Four weeks of fosfomycin therapy was successfully continued without any adverse events. In the era of antibiotic resistance, revival of forgotten drugs is an important issue for clinicians. Fosfomycin can be applied as an alternative option for prostate infections, considering the remaining susceptibility of multidrug-resistant pathogens to fosfomycin and the good pharmacokinetics of this drug in prostatic tissue.

DOI： 10.2169/internalmedicine.53.3098

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We describe a rare case of recurrent Stenotrophomonas maltophilia bacteremia in a previously healthy 45-year-old man. The infection was caused by osteomyelitis at the site of an iliac crest bone graft harvest. A genetic analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed that the blood isolates and pathogens obtained from the surgical wound were identical. Initial treatment with levofloxacin and cefozopran was ineffective, but the patient's infection was successfully treated by long-term administration of latamoxef and trimethoprim-sulfamethoxazole. The present case suggests that attention should be given to the possibility of S. maltophilia infection in any situations.

DOI： 10.2169/internalmedicine.53.1995

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DOI： 10.2169/internalmedicine.53.2734

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We herein describe a case of Wuchereria bancrofti infection in a previously healthy 37-year-old Nepalese man. The patient presented with a history of milky urine with subsequent acute urinary retention lasting for a few days. The presence of microfilariae was confirmed on both peripheral blood and urine smears obtained at midnight. He was conservatively treated with diethylcarbamazine combined with doxycycline. Filariasis was previously endemic in southern parts of Japan, although it has been eradicated. Clinicians should remember filariasis as a potential etiology of urinary retention, especially in cases that may be associated with imported infectious disease.

DOI： 10.2169/internalmedicine.53.2572

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DOI： 10.2169/internalmedicine.53.2772

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We herein present a rare case of Actinomyces meyeri-induced meningitis that occurred in a patient of advanced age with poor oral hygiene. Although Gram staining of the cerebrospinal fluid (CSF) revealed Grampositive rods and a blood culture was positive for the organism, a bacterial culture of the CSF was negative. Anaerobic cultures of CSF specimens are not routinely performed; however, anaerobes are sometimes involved in central nervous system infection. We therefore believe that anaerobic cultures should be considered in high-risk cases, such as those involving necrotizing bowel lesions or poor oral hygiene. A negative result on a CSF culture can result in misdiagnosis and inappropriate treatment.

DOI： 10.2169/internalmedicine.53.0403

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Acute generalized exanthematous pustulosis (AGEP) is a self-limiting type of drug eruption that frequently occurs as a reaction to antibiotics, particularly penicillins or macrolides. Daptomycin (DAP) is a newly developed antibiotic that specifically targets methicillin-resistant Staphylococcus aureus infection. We herein present the case of a 77-year-old severe burn victim who was diagnosed with DAP-induced AGEP while receiving treatment in an intensive care unit. Although rare, physicians should be aware that the administration of DAP can cause AGEP, which may complicate the clinical course of patients with a high fever and inflammation.

DOI： 10.2169/internalmedicine.53.0679

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DOI： 10.2169/internalmedicine.53.1346

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Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is genetically heterogeneous and various genotypes are spreading worldwide. We herein report a case of systematically disseminated Japan-intrinsic CA-MRSA infection that was successfully treated. A genetically identical single strain was isolated from a total of 11 different parts of the patient's body, and the pathogen was found to be multilocus sequence type 8, staphylococcal cassette chromosome mec IV, coagulase type III and negative for both Panton-Valentine leukocidin and arginine catabolic mobile element. The epidemiology and pathogenicity of the Japan-intrinsic CA-MRSA strain remain unknown, and further investigation of this life-threatening organism is warranted.

DOI： 10.2169/internalmedicine.53.1746

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A 38-year-old woman was admitted to our hospital because she experienced cardiopulmonary arrest at her wedding;her cardiac beats were resumed 20 min after cardiopulmonary resuscitation performed by her relatives and hotel staffs. Enhanced computed tomography revealed acute aortic redissection in chronic dissecting aneurysm in the right sinus of Valsalva, which was believed to have occurred in the 4th month of pregnancy 2 years before. Echocardiography showed moderate aortic regurgitation. We performed aortic valve-sparing operation and ascending aortic replacement with partial remodeling of the right sinus of Valsalva. She returned to work 2 months later without high-order dysfunction.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Varicella-zoster virus (VZV) usually causes localized zoster in adults. However, in immunocompromised patients, it can cause systemic infection accompanied by complications such as pneumonia, encephalitis, and hepatitis. Although most of critically ill patients in intensive care unit (ICU) are immunologically compromised, they are usually not considered to be at risk for systemic VZV infection.
We report two cases of systemic VZV infection occurring in critically ill patients in an ICU. One patient was a 69-year-old man with Streptococcus pneumoniae-induced purpurafulminans, and the other was a 75-year-old woman with severe acute pancreatitis. During the clinical course in the ICU, characteristic vesicles with umbilical fossa appeared diffusely and bilaterally on their face, trunk, and extremities. VZV-specific IgG levels were confirmed to be elevated compared to that of the pre-onset, and a diagnosis of recurrent VZV infection was made in both patients. The patients were treated at the same ICU but did not coincide with each other; therefore a cross-infection was unlikely. They were treated with intravenous acyclovir, but the latter patient eventually died of respiratory failure.
VZV infection can cause a number of serious complications, and can lead to death in some patients. Early detection and proper treatment are needed to prevent the infection from spreading out and save the patients. It might be necessary to consider antiviral prophylaxis against VZV infection for a part of critically ill patients in ICU, although the effectiveness of this approach is yet to be established.

DOI： 10.1186/1743-422X-10-225

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Language：Japanese   Publishing type：Research paper (scientific journal)  

This report focuses on 3 cases of traumatic aortic dissection or rupture at the isthmus. We selected 3 different methods of treatment. In the 1st case, we performed an emergency operation with graft replacement of the proximal descending aorta. In the 2nd case, we performed elective graft replacement 5 months after the rupture under careful blood pressure control. Thirdly, we performed emergency stent grafting at the isthmus, the rupture site. All cases were successfully treated, but it remains difficult to select the method of treatment for multisystem disorder. Our current strategy for traumatic rupture at the isthmus is immediate stent grafting. It will also be a very useful procedure for multisystem trauma.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

The clinical picture of Ochrobactrum anthropi infection is not well described because the infection is rare in humans and identification of the pathogen is difficult. We present a case of O. anthropi bacteremia that was initially misidentified as Ralstonia paucula and later identified by 16S rRNA sequencing and recA analysis.

DOI： 10.1128/JCM.03238-12

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

A 95-year-old man with chronic obstructive pulmonary disease and chronic hepatitis C virus infection was treated for acute lung injury caused by Chlamydophila pneumoniae with antibiotics and high-dose corticosteroids. In total, 7,500 mg methylprednisolone and 680 mg prednisolone were administered over 21 days. However, respiratory failure progressed, and chest computed tomography (CT) scan showed bilateral ground-glass opacity and cavity-forming consolidation in the right upper lobe. Despite intensive therapy, the patient died of multiple organ failure on day 7. CT-guided necropsy was performed, and pathological examination revealed invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonia. Invasive pulmonary aspergillosis and P. jirovecii pneumonia are both life-threatening opportunistic fungal infections. Co-infection of these organisms is rare but possible if the patient is in an extremely immunocompromised state. Short-term but high-dose systemic corticosteroid therapy was considered to be the risk factor in this case. We should pay more attention to immunocompromised hosts who might be suffering from co-infection of opportunistic infections. Moreover, we need to consider preventive measures in such high-risk cases.

DOI： 10.1007/s10156-012-0473-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

A 46-year-old woman was transferred to our emergency unit because of impaired consciousness and respiratory failure with the history of excessive pesticide intake. The patient was hypersalivative and had bilateral pupillary miosis. Laboratory results showed markedly decreased cholinesterase. She was intubated and treated in the intensive care unit with the diagnosis of organophosphorus poisoning. The patient had persisted diarrhea, with a high fever and stomach tenderness on day 10. Whole-body contrast enhanced computed tomography revealed a swollen, enhanced small intestinal wall, and blood culture identified Delftia acidovorans. She was diagnosed as D. acidovorans bacteremia, probably caused by bacterial translocation based on the clinical presentation and the exclusion of other sources, and treated well with a total of 8 days of antibiotic therapy. So far as we know, this is the first case of D. acidovorans bacteremia that was presumably caused by bacterial translocation after organophosphorus poisoning in an immunocompetent adult patient.

DOI： 10.1007/s10156-012-0472-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

We herein present the case of a 69-year-old Japanese man who had unprotected sexual contact with a local commercial sex worker in an East Asian country and was diagnosed as having disseminated gonococcal infection (DGI). The organism was confirmed to be Neisseria gonorrhoeae based on 16S rRNA sequencing and positive results for the cppB gene. This case indicates that a diagnosis of DGI should also be considered in elderly individuals. DGI potentially causes many complications, and the pathogen has recently been reported to be resistant to various antibiotics. Physicians must therefore pay more attention to the possible occurrence of DGI in various clinical settings.

DOI： 10.2169/internalmedicine.52.1033

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Methicillin-resistant Staphylococcus aureus is still a great concern, and recognition of the carrier is essential for appropriate infection control in intensive care units. The utility of wet swab compared to dry swab as an intranasal screening test has not been well assessed yet. A comparative study of the wet and dry swab in its ability to detect the organism was performed against critically ill patients, and it was found that there were no statistically significant differences between the two different methods. The wet swab did not show increased sensitivity compared to dry one.

DOI： 10.1186/2052-0492-1-10

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An emphysematous liver abscess is a fatal condition that often occurs in patients with uncontrolled diabetes mellitus. I herein describe two cases of Klebsiella pneumoniae-induced emphysematous liver abscesses complicated by septic pulmonary emboli in patients with poorly controlled diabetes mellitus. Both patients showed hemoglobin A1c levels of more than 10% and did not present with any abdominal symptoms on admission. However, they were diagnosed and successfully treated with percutaneous transhepatic abscess drainage and antibiotics. This fatal disease should be taken into consideration in patients with uncontrolled diabetes mellitus who suffer from prolonged fevers and uncharacteristic general malaise. © 2013 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.52.8737

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A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality. © 2013 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.52.0499

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

An 88-year-old man died of streptococcal toxic shock syndrome due to a group G streptococcus infection that was possibly caused by an intramuscular injection given 30 hours earlier in his right deltoid muscle. The causative pathogen was later identified to be Streptococcus dysgalactiae subsp. equisimilis (stG485). Although providing intramuscular injections is an essential skill of health care workers that is performed daily worldwide, it may constitute a port of entry for pathogens via skin breaches that can cause life-threatening infections. All invasive procedures should be carefully performed, especially when immunologically compromised patients are involved.

DOI： 10.2169/internalmedicine.52.8846

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An 86-year-old woman with diabetes mellitus and severe decubitus at the sacral and calcaneal regions stemming from poor daily activity was diagnosed with pyometra perforation caused by Actinomyces. No foreign materials, including an IUD, were found inside the uterus. Pyometra is usually caused by Enterobacteriaceae or anaerobes derived from the gastrointestinal tract. The virulence of Actinomyces is rather low, and, in almost all the reported cases of Actinomyces-related pyometra, an intrauterine device (IUD) was involved. Although rare, Actinomyces may be ascribed as a virulent pathogen that causes pyometra in the absence of foreign materials.

DOI： 10.1155/2013/658902

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

We herein report the case of an 85-year-old woman presenting with right internal jugular vein candidal thrombophlebitis associated with central venous catheters (CTCVC). The infecting agent was Candida albicans, which caused recurrent candidemia five times in total. Micafungin (MCFG) alone was ineffective; however, the combination of MCFG with fosfluconazole (F-FLCZ) successfully treated the patient without a need for any anticoagulant or surgical therapies. To the extent of our knowledge, this is the first report of CTCVC being successfully treated with a combination of F-FLCZ and MCFG. These new antifungal agents have better efficacy, tolerability and bioavailability; therefore, they can be useful alternatives to classical combination therapies such as amphotericin-B and 5-fluorocytosine.

DOI： 10.2169/internalmedicine.52.0584

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A 73-year-old man with long-term food deprivation and total parenteral nutrition was diagnosed with septic pulmonary emboli (SPE) and a persistent bacteremia caused by central line-associated blood stream methicillin-resistant Staphylococcus aureus (MRSA) infection. Although daptomycin (DAP) failed to treat the persistent bacteremia, linezolid successfully controlled it. DAP is inactivated by lung surfactant, and therefore, it should not be administered for lower respiratory infections. However, SPE caused by MRSA has been reported to be treatable with DAP since it is an infection of the lung parenchyma. We herein report the lack of effect of daptomycin in SPE treatment.

DOI： 10.2169/internalmedicine.52.0023

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 21-year-old Japanese man with a history of marked body weight loss over a short period of time died of necrotizing duodenitis caused by Clostridium perfringens (C. perfringens) type A. C. perfringens type A is considered to usually cause self-limiting gastroenteritis. Necrotizing enteritis sometimes occurs due to C. perfringens in developing countries; however, it is primarily caused by the type C strain and its site of onset is typically the jejunum or ileum. This is a rare case of necrotizing duodenitis caused by C. perfringens type A in a Japanese young man. Physicians need to be more aware of this emerging fatal disease in developed countries.

DOI： 10.2169/internalmedicine.51.8407

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE