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Study on the efficacy of Rifabutin for M. abscessus group

Research Project

Project/Area Number 20K22755
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0803:Pathology, infection/immunology, and related fields
Research Institution公益財団法人結核予防会 結核研究所

Principal Investigator

Kamada Keisuke  公益財団法人結核予防会 結核研究所, 臨床・疫学部, 医員 (80885666)

Project Period (FY) 2020-09-11 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsM. abscessus group / 迅速発育性抗酸菌 / M. abscessus / Rifabutin / rifabutin / 迅速発育抗酸菌 / 薬剤感受性
Outline of Research at the Start

M. abscessus group 感染症は難治性であり新規治療薬の探索が喫緊の課題である。rifabutinも近年、治療薬の候補として注目が高まっているがその評価は定まっていない。本研究では日本で臨床分離されたM. abscessus group を対象にrifabutinの薬剤感受性とRifampicin-resistance determining region (RRDR)領域の遺伝子変異の関係性だけでなく感受性株と耐性株のwhole genome sequenceを比較することでRRDR領域以外の遺伝子学的な差異に関しても評価し、rifabutinの治療薬としての可能性を検討する。

Outline of Final Research Achievements

We reported on 320 clinical isolates of M. abscessus species, showing that M. abscessus, a more drug-resistant subspecies, may be more susceptible to rifabutin than M. massiliense. Furthermore, the synergistic effect of the combination of rifabutin and omadacycline was demonstrated in an experiment using bacterial isolates. To investigate the difference in susceptibility to rifabutin between strains, we analyzed the gene sequence of the rifampicin-resistance determining region (RRDR), and found that the amino acid sequence was identical in all clinical isolates. Because of a series of reports of decreased rifabutin MIC in ADP-ribosyltransferase (Arr) gene (MAB_0591) knockout strains, we decided to investigate the gene and amino acid sequence of MAB_0591 and its promoter region in clinical isolates, and are currently analyzing the results.

Academic Significance and Societal Importance of the Research Achievements

高度薬剤耐性を有するM. abscessus感染症の治療は非常に難しい。通常、薬剤感受性が担保された3-4種類の抗菌薬を併用した上で最短でも数ヶ月以上の治療期間が必要とするが、特に内服できる治療薬の選択肢は極めて限られており、Rifabutinにかかる期待は大きい。代表者らのM. abscessusに対するRifabutinの薬剤感受性評価は過去最大規模のものである。また、近年海外で効果が注目されているomadacyclineとの併用で治療相乗効果が期待されることも臨床的に重要性の高い発見であり今後の臨床研究での評価が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021 2020

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] In Vitro Synergistic Effects of Omadacycline with Other Antimicrobial Agents against Mycobacterium abscessus2023

    • Author(s)
      Keiji Fujiwara, Akio Aono, Takahiro Asami, Kozo Morimoto, Keisuke Kamada, Yuta Morishige, Yuriko Igarashi, Kinuyo Chikamatsu, Yoshiro Murase, Hiroyuki Yamada, Akiko Takaki, Satoshi Mitarai
    • Journal Title

      Antimicrobial agents and chemotherapy

      Volume: online ahead

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nationwide surveillance of antimicrobial susceptibility of 509 rapidly growing mycobacteria strains isolated from clinical specimens in Japan.2021

    • Author(s)
      Kamada K, Yoshida A, Iguchi S, Arai Y, Uzawa Y, Konno S, Shimojima M, Kikuchi K.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 12208-12208

    • DOI

      10.1038/s41598-021-91757-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Geographical distribution and regional differences in 532 clinical isolates of rapidly growing mycobacterial species in Japan.2021

    • Author(s)
      Kamada K,Yoshida A, Iguchi S, Arai Y, Uzawa Y, Konno S, Shimojima M, Kikuchi K.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 4960-4960

    • DOI

      10.1038/s41598-021-84537-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nationwide surveillance of antimicrobial susceptibility of 509 rapidly growing mycobacteria strains isolated from clinical specimens in Japan2021

    • Author(s)
      Kamada Keisuke、Yoshida Atsushi、Iguchi Shigekazu、Arai Yuko、Uzawa Yutaka、Konno Satoshi、Shimojima Masahiro、Kikuchi Ken
    • Journal Title

      Research Square

      Volume: -

    • DOI

      10.21203/rs.3.rs-269825/v1

    • Related Report
      2020 Research-status Report
    • Open Access
  • [Journal Article] Pulmonary infection due to fluoroquinolone-resistant Mycolicibacterium fortuitum: a case report.2020

    • Author(s)
      Kurokawa K, Harada N, Sasano H, Takagi H, Takei S, Nakamura A, Kamada K, Yoshida A, Kikuchi K, Takahashi K.
    • Journal Title

      BMC Infect Dis

      Volume: 20 Issue: 1 Pages: 866-866

    • DOI

      10.1186/s12879-020-05596-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 迅速発育性抗酸菌の薬剤感受性と治療薬選択2022

    • Author(s)
      鎌田 啓佑
    • Organizer
      第71回日本感染症学会東日本地方会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2020-09-29   Modified: 2024-01-30  

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