Faculty Profiles - HAGIYA Hideharu

Papers - HAGIYA Hideharu

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Iatrogenic fever of unknown origin. International journal

Shinnosuke Fukushima, Hideharu Hagiya, Keiji Yunoki, Gentaro Kato, Shinichi Mukai

Internal and emergency medicine 2025.3

Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital

Kazuyoshi Gotoh, Shinnosuke Fukushima, Hideharu Hagiya, Shuma Tsuji, Koji Iio, Osamu Matsushita

IJID Regions 14 100511 - 100511 2025.3

Intention and potential determinants of COVID-19 vaccination among healthcare workers at a single university hospital in Japan, 2024–2025 pre-season

Hideharu Hagiya, Yasushi Fujita, Takashi Kiguchi, Yohei Manabe

Journal of Infection and Chemotherapy 31 ( 3 ) 102660 - 102660 2025.3

A fatal case of enterovirus A71-induced meningoencephalitis following allogenic hematopoietic stem cell transplantation. International journal

Yayoi Ueda, Hiroki Kobayashi, Hideaki Fujiwara, Hideharu Hagiya, Risa Hashida, Saya Kubota, Mami Takemoto, Kenta Hayashino, Kanako Fujiwara, Tomohiro Nagano, Ryuichiro Hiyama, Keiko Fujii, Takumi Kondo, Keisuke Seike, Noboru Asada, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Maeda Yoshinobu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 31 ( 4 ) 102630 - 102630 2025.1

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

Enterovirus A71 (EV-A71) is a major pathogen responsible for hand, foot, and mouth disease (HFMD) in infants and children. EV-A71 infection represents an epidemic in the Asia-Pacific region, and can cause serious central nervous system (CNS) infections in immunocompromised patients that can result in paralysis, disability, or death. There have been few reports in the literature concerning EV-A71 CNS infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients. We describe the case of a 63-year-old woman with EV-A71 meningoencephalitis who underwent a second allo-HSCT for relapsed refractory myelodysplastic syndrome. She developed disturbance of consciousness during intubation due to severe pulmonary impairment following allo-HSCT. Despite the absence of pleocytosis in the cerebrospinal fluid, enterovirus was detected in her cerebral spinal fluid using the Biofire® FilmArray® Meningitis/Encephalitis (ME) panel, which was later identified as EV-A71 at a referral center. Despite a transient improvement in her level of consciousness after intravenous immunoglobulin administration, she did not fully recover. The patient also showed muscle weakness as well as pulmonary impairment that necessitated a tracheotomy. Our case demonstrated the utility of the FilmArray® ME panel as a screening tool for detecting multiple potential pathogens until a specific pathogen could be identified using other diagnostic methods. Clinicians should be aware that EV-A71 CNS infection can occur among adults with severe immunodeficient conditions, and that it leads poor clinical outcomes. Our case suggests that continuous monitoring for this potentially fatal pathogen is warranted for immunocompromised patients.

DOI： 10.1016/j.jiac.2025.102630

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Odontogenic cervical intramedullary abscesses. International journal

Shinnosuke Fukushima, Hideharu Hagiya

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 133 111026 - 111026 2024.12

International trends in biliary tract cancer-related mortality, 2000-2022: An observational study of the World Health Organization mortality database. International journal

Quynh Thi Vu, Yoshito Nishimura, Ko Harada, Hiroki Ito, Tsukasa Higashionna, Akinari Maruo, Keisaku Harada, Tatsuaki Takeda, Hirofumi Hamano, Yoshito Zamami, Hideharu Hagiya, Toshihiro Koyama

Hepatology (Baltimore, Md.) 2024.12

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

BACKGROUND AIMS: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. APPROACH RESULTS: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000-2022 based on available data from countries. Trends in age-standardised mortality rates (ASRs) during 2013-2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% confidence interval: 2.5-3.1) in 2000, and 2.7 (2.3-3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8-6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3-2.9) and 2.2 (1.8-2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to GBC decreased by 45.5%, and those due to eCCA remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013-2022, with iCCA-associated ASRs showing increasing trends in many countries. CONCLUSIONS: Although internationally estimated BTC-associated ASRs showed a stable trend over the last two decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.

DOI： 10.1097/HEP.0000000000001200

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Trends in the growing impact of group A Streptococcus infection on public health after COVID-19 pandemic: a multicentral observational study in Okayama, Japan. International journal

Shinnosuke Fukushima, Takashi Saito, Yoshitaka Iwamoto, Yuko Takehara, Haruto Yamada, Koji Fujita, Masayo Yoshida, Yasuhiro Nakano, Hideharu Hagiya

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2024.12

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

PURPOSE: Following the COVID-19 pandemic, group A Streptococcus (GAS) infection has been surging worldwide. We aimed to compare the disease burden between notified cases of streptococcal toxic shock syndrome (STSS) and unreported GAS infections. METHODS: This is a multicentral observational study, retrospectively performed at seven hospitals in Okayama prefecture in Japan from January 2022, to June 2024. Clinical and microbiological data of patients with positive cultures of GAS were collected from the medical records. Primary outcomes were defined as rates of surgical procedures, intensive care unit (ICU) admission, and in-hospital mortality, which were compared among patients with locally-defined STSS, invasive GAS (iGAS), and non-iGAS infection. RESULTS: GAS was detected in 181 patients, with 154 active cases of GAS infection. The number of patients with GAS infection surged in late 2023. The most common source of infection was skin and soft tissue infections, accounting for 83 cases, including 15 cases of necrotizing fasciitis, and 12 cases (7.8%) were notified to public health authorities as STSS. Among the 25 unreported iGAS cases, 9 (36.0%) underwent surgical intervention, and 4 patients (16.0%) required ICU admission. The mortality rates in the unreported iGAS cases were comparable to those observed in the notified STSS. CONCLUSIONS: We highlighted that the number of iGAS infections was twofold higher than that of notified STSS, with comparable mortality rate between these groups, indicating substantial underestimation of the true burden of iGAS. This epidemiological investigation has significant implications for enhancing infectious disease surveillance frameworks and public health policy development.

DOI： 10.1007/s10096-024-05015-2

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Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Kazuyoshi Gotoh, Shuma Tsuji, Koji Iio, Hidemasa Akazawa, Osamu Matsushita, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. METHODS: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including "Corynebacterium", "Daptomycin", and "Resistance", in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. RESULTS: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8%), and prosthetic device-associated infections accounted for 66.7% of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71% to 100%) within 24 hours of incubation, compared to other Corynebacterium strains CONCLUSION: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.

DOI： 10.1016/j.jiac.2024.12.004

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Epidemiology and Clinical Features of Patients with Tick Bites in the Japanese Spotted Fever-Endemic Zone. Reviewed International journal

Shinnosuke Fukushima, Takaomi Sumida, Osamu Kawamata, Yoshimi Hidani, Hideharu Hagiya

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024.12

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: This study aimed to clarify the epidemiology and clinical features of tick bites in a Japanese spotted fever (JSF)-endemic area. METHOD: The clinical records of patients with tick bites were retrospectively reviewed based on a survey conducted at Numakuma Hospital, Fukuyama City, Hiroshima, Japan, from 2016-2023. Data on basic characteristics, visit dates, residential address, exposure activities, tick-bite sites, and prophylactic antimicrobial prescriptions for each patient with tick bites were collected at the JSF hotspot hospital. RESULTS: A total of 443 patients with tick bites visited the hospital, of which data on 305 cases (68.8%) were reviewed. The median age of these patients was 71 years, with a higher proportion of women (63.0%). One-third of the patients had a preceding history of working in fields, whereas two-thirds had entered mountains or agricultural fields. Nearly 90% of the patients visited the hospital from April to August, and the most common bite sites were the lower extremities (45.1%). Most patients (76.1%) resided in the southern area of Numakuma Hospital. Nearly all patients were prescribed prophylactic antibiotics (minocycline in 87.8% of cases), and none subsequently developed JSF. CONCLUSION: Continued surveillance of patients with tick bites is warranted to better understand changes in the clinical impact of tick-borne diseases.

DOI： 10.1016/j.jiac.2024.11.020

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Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic. Reviewed International journal

Yasue Sakurada, Yui Matsuda, Kanon Motohashi, Toru Hasegawa, Yuki Otsuka, Yasuhiro Nakano, Kazuki Tokumasu, Koichiro Yamamoto, Naruhiko Sunada, Hiroyuki Honda, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Journal of psychosomatic obstetrics and gynaecology 45 ( 1 ) 2305899 - 2305899 2024.12

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

PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated. METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances. RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints. CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

DOI： 10.1080/0167482X.2024.2305899

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Detailed regimens for the prolonged β-lactam infusion therapy. Reviewed International journal

Hideharu Hagiya

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 12 ) 1324 - 1326 2024.12

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

A recent systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of prolonged versus intermittent β-lactam infusion in adult sepsis patients. The findings revealed a significant decrease in all-cause mortality and marked clinical success in the prolonged infusion group. Unfortunately, however, the manuscript lacked data and discussion for the specific regimens of prolonged β-lactam infusion defined in the included 15 RCT studies, which are herein additionally provided. Excluding one RCT, all protocols adopted a continuous infusion for the prolonged treatment. Except for three RCTs, dosages and timings of bolus injection were clearly defined. The total daily antibiotic dose for the continuous therapy was equivalent to those recommended for intermittent therapy. We believe this supplementary data aids clinicians in providing prolonged β-lactam infusions, contributing to enhanced treatment outcomes for patients suffering from severe sepsis or septic shock.

DOI： 10.1016/j.jiac.2024.07.003

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日本紅斑熱好発地域におけるヒト吸血をきたしたダニ種および保有病原体の検討

福島伸乃介, 後藤和義, 辻秀真, 角南博, 中野靖浩, 中本健太, 萩谷英大

日本臨床微生物学会雑誌 35 ( Suppl.1 ) 306 - 306 2024.12

Human Papillomavirus vaccination awareness and uptake among healthcare students in Japan. Reviewed International journal

Madoka Shimbe, Yuki Otsuka, Hideharu Hagiya, Yoichi Yamada, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2024.11

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The vaccination rate for HPV (Human Papillomavirus) has remained significantly low in Japan because of the administrative suspension of active recommendation. This study investigates the awareness and uptake of the HPV vaccine among healthcare students in Japan following the reinstatement of active recommendation for young women in April 2022. METHODS: A web-based survey was administered to 2567 healthcare students from Okayama and Shujitsu Universities in Japan in July 2023. The survey assessed participants' backgrounds, immunization status, awareness of vaccine recommendations, and knowledge of cervical cancer across various demographics, including sex, academic year, and department (Medicine, Health Science, Pharmaceutical, and Dentistry). RESULTS: The response rate was 36.3 % (933 students; 181 male, 739 female, and 13 unspecified gender). The overall immunization rate among female students was 55.6 %, with higher rates observed in medical (73.8 %) and dental (63.0 %) students. Awareness of the government's change in vaccine recommendation was notably high among female and senior male students. Over half of the female students (54.7 %) reported receiving vaccinations based on their parents' advice. Among those unvaccinated but interested in future immunization, concerns about adverse reactions (47.4 %) and challenges in scheduling vaccinations (29.1 %) were predominant. CONCLUSION: Healthcare students exhibited a higher HPV vaccination rate than the general population. Ongoing education to improve vaccine literacy is crucial for augmenting HPV vaccination rates in Japan.

DOI： 10.1016/j.jiac.2024.11.004

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Letter to the Editor: "Real-World Effectiveness of Ensitrelvir in Reducing Severe Outcomes in Outpatients at High Risk for COVID-19". Reviewed International journal

Hideharu Hagiya

Infectious diseases and therapy 13 ( 11 ) 2461 - 2462 2024.11

Ethical consumption of antimicrobial agents: A proposal for a new concept in promoting antimicrobial stewardship. Reviewed International journal

Hideharu Hagiya

The American journal of the medical sciences 368 ( 5 ) 553 - 555 2024.11

Addressing the Rejection of a Rebuttal Letter: Author's Experience and Thoughts. Reviewed

Hideharu Hagiya

JMA journal 7 ( 4 ) 628 - 629 2024.10

Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital. Reviewed

Kazuyoshi Gotoh, Makoto Miyoshi, I Putu Bayu Mayura, Shuma Tsuji, Koji Iio, Shinnosuke Fukushima, Osamu Matsushita, Hideharu Hagiya

Acta medica Okayama 78 ( 5 ) 371 - 376 2024.10

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control.

DOI： 10.18926/AMO/67657

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Threat of MRSA bacteremia still matters: a propensity score matching analysis. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Naoki Kuninaga, Yuto Haruki, Haruto Yamada, Yoshitaka Iwamoto, Masayo Yoshida, Kota Sato, Yoshihisa Hanayama, Shuichi Tanaka, Tomoko Miyoshi, Yuki Otsuka, Keigo Ueda, Fumio Otsuka

Infection 2024.9

Cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus clinical isolates Reviewed International journal

Shuma Tsuji, Kazuyoshi Gotoh, Tadahiro Manabe, Koji Iio, Shinnosuke Fukushima, Osamu Matsushita, Hideharu Hagiya

Diagnostic Microbiology and Infectious Disease 110 ( 1 ) 116399 - 116399 2024.9

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

We investigated the prevalence and characteristics of Cefazolin inoculum effect (CInE) among clinical MSSA isolates in Japan. Although 35.5 % (39 isolates) were positive for the blaZ gene, none met the phenotypic criteria for CInE. Our findings suggested a very low prevalence of CInE among MSSA isolates in our clinical setting.

DOI： 10.1016/j.diagmicrobio.2024.116399

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出血性脳梗塞,肺塞栓,深部静脈血栓症を合併したCOVID-19の1例

長谷川功, 山本紘一郎, 中本健太, 平佑貴, 庵谷紘美, 中野靖浩, 萩谷英大, 大塚文男

日本病院総合診療医学会雑誌 20 ( 5 ) 289 - 294 2024.9

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

52歳男性。COVID-19発症7日後に経皮的動脈血酸素飽和度94%(リザーバー10L/分投与下),右眼球共同偏倚と左半側空間無視,左上下肢完全麻痺をきたし搬送された。単純CTでは頭部で右中大脳動脈領域低吸収域を認め,胸部では両側広範囲の末梢優位のすりガラス影を認めた。造影CTでは右下肺動脈と左大腿静脈・膝窩静脈に血栓を認め,脳梗塞と肺塞栓症・深部静脈血栓症を合併した重症COVID-19と診断した。経過中に出血性脳梗塞を発症するも救命し得た。脳梗塞・肺塞栓を合併したCOVID-19では出血性脳梗塞の発症を念頭に慎重なフォローが必要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J05937&link_issn=&doc_id=20241218260009&doc_link_id=10.60227%2Fjhgmwabun.20.5_289&url=https%3A%2F%2Fdoi.org%2F10.60227%2Fjhgmwabun.20.5_289&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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Papers - HAGIYA Hideharu