Faculty Profiles - HAGIYA Hideharu

Papers - HAGIYA Hideharu

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Antibiotic-associated adverse drug events at a Japanese academic hospital. Reviewed International journal

Ryohei Kokado, Hideharu Hagiya, Toshihiro Koyama, Eiko Matsui, Hideo Okuno, Daiichi Morii, Shigeto Hamaguchi, Hisao Yoshida, Yoshihiro Miwa, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 5 ) 392 - 395 2019.5

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

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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Association between rapid antigen detection tests and antibiotics for acute pharyngitis in Japan: A retrospective observational study. Reviewed International journal

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Ayako Ohshima, Yoshito Zamami, Yasuhisa Tatebe, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 4 ) 267 - 272 2019.4

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

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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Repeated Left Upper Abdominal Pain. Reviewed

Kazuhiro Hongyo, Futoshi Nakagami, Hideharu Hagiya, Hiromi Rakugi

Internal medicine (Tokyo, Japan) 58 ( 6 ) 893 - 893 2019.3

Fastidious spiral bacilli causing backbone infections after gastroenteritis. International journal

Koichiro Lee, Hideharu Hagiya, Misaki Kageyama, Futoshi Nakagami

BMJ case reports 12 ( 3 ) 2019.3

Spreading Patterns of NDM-Producing Enterobacteriaceae in Clinical and Environmental Settings in Yangon, Myanmar. Reviewed International journal

Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Noriko Sakamoto, Dan Takeuchi, Rathina Kumar Shanmugakani, Daisuke Motooka, Isao Nishi, Khwar Nyo Zin, Mya Mya Aye, Thuzar Myint, Kazunori Tomono, Shigeyuki Hamada

Antimicrobial agents and chemotherapy 63 ( 3 ) 2019.3

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

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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Mycobacterium avium complex infection mimicking lung cancer. International journal

Hideharu Hagiya

BMJ case reports 12 ( 2 ) 2019.2

PCR-Dipstick-Oriented Surveillance and Characterization of mcr-1- and Carbapenemase-Carrying Enterobacteriaceae in a Thai Hospital. Reviewed International journal

Rathina Kumar Shanmugakani, Yukihiro Akeda, Yo Sugawara, Warawut Laolerd, Narong Chaihongsa, Suntariya Sirichot, Norihisa Yamamoto, Hideharu Hagiya, Daiichi Morii, Yoshihiro Fujiya, Isao Nishi, Hisao Yoshida, Dan Takeuchi, Noriko Sakamoto, Kumthorn Malathum, Pitak Santanirand, Kazunori Tomono, Shigeyuki Hamada

Frontiers in microbiology 10 149 - 149 2019.2

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

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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An uncommon cause of leg oedema. Reviewed International journal

Naito T, Hagiya H, Nakagami F, Yamamoto K

BMJ case reports 12 ( 1 ) 2019.1

Acute Non-calcific Retropharyngeal Tendinitis. Reviewed

Futoshi Nakagami, Hideharu Hagiya, Hiromi Rakugi

Internal medicine (Tokyo, Japan) 57 ( 23 ) 3499 - 3500 2018.12

Persistent methicillin-resistant Staphylococcus aureus bacteremia owing to placental abscess. Reviewed International journal

Naomi Maeda, Hideharu Hagiya, Tsuyoshi Takiuchi, Shinsuke Kusakabe, Tetsuo Maeda, Keigo Kimura, Sayuri Iwai, Keisuke Kawasaki, Yumiko Hori, Eiichi Morii, Yuzuru Kanakura, Tadashi Kimura, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 ( 12 ) 975 - 979 2018.12

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

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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Swollen Extraocular Muscle and Tingling Extremities. Reviewed International journal

Futoshi Nakagami, Hideharu Hagiya, Akane Oyama, Kazuhiro Hongyo, Motonori Nagasawa, Hiromi Rakugi

The American journal of medicine 131 ( 12 ) e492-e493 2018.12

Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed International journal

Hiroshi Onoue, Toshihiro Koyama, Yoshito Zamami, Hideharu Hagiya, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Yasuyoshi Ouchi, Mitsunobu R Kano

Journal of the American Geriatrics Society 66 ( 12 ) 2267 - 2273 2018.12

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

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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Oral shingles. Reviewed International journal

Hagiya H, Nakagami F, Isomura E

BMJ case reports 11 ( 1 ) 2018.12

Emergence of daptomycin non-susceptible coagulase-negative Staphylococci in patients with cardiovascular device infections: Two cases report investigated by whole genome analysis. Reviewed International journal

Hagiya H, Sugawara Y, Kimura K, Hamaguchi S, Nishi I, Hayashi M, Akeda Y, Tomono K

Medicine 97 ( 49 ) e13487 2018.12

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

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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Daptomycin-associated myopathy induced by concomitant administration of mirabegron. Reviewed International journal

Hagiya H, Kokado R, Okuno H, Tomono K

Infection 47 ( 2 ) 331 - 332 2018.11

Trends in incidence and mortality of tuberculosis in Japan: a population-based study, 1997-2016. Reviewed International journal

Hagiya H, Koyama T, Zamami Y, Minato Y, Tatebe Y, Mikami N, Teratani Y, Ohshima A, Shinomiya K, Kitamura Y, Sendo T, Hinotsu S, Tomono K, Kano MR

Epidemiology and Infection 147 1 - 10 2018.11

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

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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Broad-spectrum antibiotic prescriptions are unevenly discontinued throughout the week. Reviewed International journal

Kokado R, Hagiya H, Morii D, Okuno H, Yamamoto N, Hamaguchi S, Yoshida H, Miwa Y, Tomono K

The Journal of hospital infection 101 ( 4 ) 471 - 474 2018.11

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

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 mucosa bacteremia in a neutropenic child: A case report and literature review. International journal

Keigo Kimura, Hideharu Hagiya, Isao Nishi, Hisao Yoshida, Kazunori Tomono

IDCases 14 e00469 2018.11

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

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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Neurosyphilis concurrently involving eye and ear. Reviewed International journal

Futoshi Nakagami, Hideharu Hagiya, Kazuichi Maruyama, Yuri Onishi

BMJ case reports 2018 2018.10

Reduced Seroprevalence of Hepatitis A Virus Among Japanese Healthcare Workers as a Risk Factor for Occupational Infection. Reviewed International journal

Yoshioka N, Deguchi M, Hagiya H, Kagita M, Tomono K

Clinical laboratory 64 ( 10 ) 1791 - 1793 2018.10

Language：English

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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Papers - HAGIYA Hideharu