Molecular epidemiological analysis of drug-resistant bacteria from overseas

2023 Fiscal Year Research-status Report

• Project/Area Number: 23K09603
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 貫井 陽子 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20568232)
• Project Period (FY): 2023-04-01 – 2026-03-31
• Keywords: 薬剤耐性菌 / アウトブレイク / 感染対策

Outline of Annual Research Achievements

薬剤耐性菌は新型コロナウイルス感染症流行禍においても”Silent Pandemic” として拡大し続け、全世界的な脅威となっている。今後ポストコロナ時代において海外からのインバウンドの再増加により日本国内においても海外で流行している薬剤耐性菌のアウトブレイクのリスクが高まっている。ひとたびアウトブレイクが生じた際には、適切な個人防護具の着用・接触予防策の開始・個室隔離・環境培養調査・遺伝子解析・保菌調査・新規入院の停止など様々な対策をバンドル（束）化して迅速に進めていく必要がある。米国では、それらの感染管理にかかる費用は年間約100億ドル、デンマークでは年間2.7億ユーロと推定されており、医療経済的な側面においても海外由来薬剤耐性菌の対応は重要である。このような状況に備えるため申請者が在籍していた病院では2019年より海外において医療歴のある患者、海外居住者、頻回の海外渡航歴を有する患者を対象に入院時耐性菌スクリーニング検査を開始した。257株のスクリーニング検体から62株の耐性グラム陰性桿菌を検出し、特に東南アジアからの患者では耐性菌検出率は48.1%と高率であった。検出された海外由来グラム陰性桿菌の内、93.5％が大腸菌、3.2%がKlebsiella pneumoniae、1.6％がKlebsiella oxytoca, Klebsiella aerogenesであった。海外由来耐性大腸菌の耐性機序は、基質特異性βラクタマーゼ(ESBL)産生が91.4%、ESBL産生とAmpC過剰産生が3.4%、カルバぺネム耐性が5.2%であった。
本研究は海外由来耐性菌の遺伝子解析、分子疫学解析を行うことで、国内流行株との差異を明らかにし、臨床的特徴・薬剤感受性結果などの情報を元に最適な治療・感染対策法の確立を目的とする。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

83株の海外由来耐性グラム陰性桿菌の菌種、耐性機序解析が終了した。

Strategy for Future Research Activity

今後は薬剤耐性遺伝子保有状況、遺伝子型解析を実施し、国内株との比較を行う。

Research Products

• [Journal Article] Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient (2024)
  • Author(s): Tanino Y, Nishioka K, Yamamoto C, Watanabe Y, Daidoji T, Kawamoto M, Uda S, Kirito S, Nakagawa Y, Kasamatsu Y, Kawahara Y, Sakai Y, Nobori S, Inaba T, Ota B, Fujita N, Hoshino A, Nukui Y, Nakaya T
  • Journal Title: Infect Drug Resist Volume: 8 Pages: 531-541
  • DOI: 10.2147/IDR.S438915
  • Peer Reviewed / Open Access
• [Journal Article] Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children (2024)
  • Author(s): Bastard P, Gervais A, Taniguchi M,, Sahanic S, Tancevski I, Nukui Y, Hayakawa S, Chrousos GP, Gonzalez-Granado LI, Kisand K, Okada S, Puel A, Cobat A, Casanova JL
  • Journal Title: J Exp Med Volume: 221 Pages: e20231353-
  • DOI: 10.1084/jem.20231353
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Negative impact of immunoparesis in response to anti-SARS-CoV-2 mRNA vaccination of patients with multiple myeloma (2024)
  • Author(s): Onishi A, Matsumura-Kimoto Y, Takahashi R, Kobayashi T, Uchiyama H, Uoshima N, Nukui Y, Shimura Y, Inaba T, Kuroda J
  • Journal Title: Int J Hematol Volume: 119 Pages: 50-61
  • DOI: 10.1007/s12185-023-03680-1
  • Peer Reviewed / Open Access
• [Journal Article] Novel insights into genetic characteristics of blaGES-encoding plasmids from hospital sewage (2023)
  • Author(s): Ota Y, Prah I, Mahazu S, Gu Y, Nukui Y, Koike R, Saito R.
  • Journal Title: Front Microbiol Volume: 14 Pages: 1209195 -
  • DOI: 10.3389/fmicb.2023.1209195
  • Peer Reviewed / Open Access
• [Journal Article] Klebsiella Species and Enterobacter cloacae Isolates Harboring blaOXA-181 and blaOXA-48: Resistome, Fitness Cost, and Plasmid Stability (2023)
  • Author(s): Mahazu S, Prah I, Ota Y, Hayashi T, Nukui Y, Suzuki M, Hoshino Y, Akeda Y, Suzuki T, Ishino T, Ablordey A, Saito R
  • Journal Title: Microbiol Spectr Volume: 11 Pages: e0052123-
  • DOI: 10.1128/spectrum.03320-22
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Viral load of SARS-CoV-2 Omicron BA.5 is lower than that of BA.2 despite the higher infectivity of BA.5 (2023)
  • Author(s): Takatsuki Y, Takahashi Y, Nakajima J, Iwasaki Y, Nagano K, Tani-Sassa C, Yuasa S, Kanehira S, Sonobe K, Nukui Y, Takeuchi H, Tanimoto K, Tanaka Y, Kimura A, Ichimura N, Tohda S
  • Journal Title: Immun Inflamm Dis Volume: 11 Pages: e783-
  • DOI: 10.1002/iid3.783
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Antibiotic Time-Outs in Multidisciplinary ICU Rounds for Antimicrobial Stewardship Program on Patient Survival: A Controlled Before-and-After Study (2023)
  • Author(s): Mishima Y, Nawa N, Asada M, Nagashima M, Aiso Y, Nukui Y, Fujiwara T, Shigemitsu H
  • Journal Title: Crit Care Explor Volume: 5 Pages: e0837-
  • DOI: 10.1097/CCE.0000000000000837
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of Treatment with Anti-CD20 Monoclonal Antibody on the Production of Neutralizing Antibody Against Anti-SARS-CoV-2 Vaccination in Mature B-Cell Neoplasms (2023)
  • Author(s): Onishi A, Matsumura-Kimoto Y, Mizutani S, Tsukamoto T, Fujino T, Miyashita A, Nishiyama D, Shimura K, Kaneko H, Kawata E, Takahashi R, Kobayashi T, Uchiyama H, Uoshima N, Nukui Y, Shimura Y, Inaba T, Kuroda J
  • Journal Title: Infect Drug Resist Volume: 25 Pages: 509-519
  • DOI: 10.2147/IDR.S396271
  • Peer Reviewed / Open Access
• [Journal Article] SARS-CoV-2 RT-PCR as a universal screening on planned admission in asymptomatic patients (2023)
  • Author(s): Yamamoto C, Nukui Y, Furukawa K, Taniguchi M, Yamano T, Inaba T, Kikai R, Tanino Y, Yamada Y, Teramukai S, Takayama K
  • Journal Title: J Infect Chemother. Volume: 21 Pages: S1341-
  • DOI: 10.1016/j.jiac.2023.12.010
  • Peer Reviewed / Open Access
• [Journal Article] Variation in presepsin and thrombomodulin levels for predicting COVID-19 mortality (2023)
  • Author(s): Yamazaki A, Nukui Y, Kameda T, Saito R, Koda Y, Ichimura N, Tohda S, Ohkawa R.
  • Journal Title: Sci Rep Volume: 13 Pages: 21493-
  • DOI: 10.1038/s41598-023-48633-0
  • Peer Reviewed / Open Access
• [Journal Article] Raman Fingerprints of SARS-CoV-2 Omicron Subvariants: Molecular Roots of Virological Characteristics and Evolutionary Directions (2023)
  • Author(s): Pezzotti G, Ohgitani E, Fujita Y, Zhu W, Inaba T, Tanino Y, Nukui Y, Higasa K, Yasukochi Y, Okuma K, Mazda O
  • Journal Title: ACS Infect Dis Volume: 9 Pages: 2226-2251
  • DOI: 10.1021/acsinfecdis.3c00312
  • Peer Reviewed / Open Access
• [Journal Article] Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2 (2023)
  • Author(s): hin-Ya M, Nakashio M, Ohgitani E, Suganami A, Kawamoto M, Ichitani M, Kobayashi M, Takihara T, Inaba T, Nukui Y, Kinugasa H, Ishikura H, Tamura Y, Mazda O
  • Journal Title: Sci Rep Volume: 13 Pages: 16577-
  • DOI: 10.1038/s41598-023-43563-3
  • Peer Reviewed / Open Access
• [Presentation] Genetic Analysis of Antimicrobial-Resistant Enterobacteriaceae in Travelers and Patients Treated Overseas (2023)
  • Author(s): Yoko Nukui
  • Organizer: ASM microbe 2023
  • Int'l Joint Research