Rifaximin potentiates clarithromycin against Mycobacterium abscessus in vitro and in zebrafish.

Autor:	Goh BC; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Larsson S; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Dam LC; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Ling YHS; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Chua WLP; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Abirami R; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Singh S; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Ong JLE; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Teo JWP; Department of Laboratory Medicine, National University Hospital, Singapore, Singapore., Ho P; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore., Ingham PW; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; Institute of Molecular and Cell Biology, Agency of Science, Technology and Research (A*Star), Singapore, Singapore., Pethe K; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore., Dedon PC; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jazyk:	angličtina
Zdroj:	JAC-antimicrobial resistance [JAC Antimicrob Resist] 2023 May 08; Vol. 5 (3), pp. dlad052. Date of Electronic Publication: 2023 May 08 (Print Publication: 2023).
DOI:	10.1093/jacamr/dlad052
Abstrakt:	Background: Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) that causes chronic pulmonary infections. Because of its extensive innate resistance to numerous antibiotics, treatment options are limited, often resulting in poor clinical outcomes. Current treatment regimens usually involve a combination of antibiotics, with clarithromycin being the cornerstone of NTM treatments. Objectives: To identify drug candidates that exhibit synergistic activity with clarithromycin against M. abscessus . Methods: We performed cell-based phenotypic screening of a compound library against M. abscessus induced to become resistant to clarithromycin. Furthermore, we evaluated the toxicity and efficacy of the top compound in a zebrafish embryo infection model. Results: The screen revealed rifaximin as a clarithromycin potentiator. The combination of rifaximin and clarithromycin was synergistic and bactericidal in vitro and potent in the zebrafish model. Conclusions: The data indicate that the rifaximin/clarithromycin combination is promising to effectively treat pulmonary NTM infections. (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
Databáze:	MEDLINE
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