Study on the efficacy of Rifabutin for M. abscessus group

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22755
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-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
• Keywords: M. abscessus group / 迅速発育性抗酸菌

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.

Free Research Field

抗酸菌感染症

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。