Rifaximin potentiates clarithromycin against Mycobacterium abscessus in vitro and in zebrafish

Boon Chong Goh, Simon Larsson, Linh Chi Dam, Yan Han Sharon Ling, Wei Lin Patrina Chua, R Abirami, Samsher Singh, Jun Long Ernest Ong, Jeanette W P Teo, Peiying Ho, Philip W Ingham, Kevin Pethe, Peter C Dedon

Research output: Contribution to journalArticlepeer-review

3 Citations (SciVal)

Abstract

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.

Original languageEnglish
Article numberdlad052
Number of pages6
JournalJAC-Antimicrobial Resistance
Volume5
Issue number3
Early online date8 May 2023
DOIs
Publication statusPublished - 1 Jun 2023

Bibliographical note

Funding Information:
This work was funded by the A*STAR Singapore Therapeutics Development Review (H19H0G1003), the Singapore-MIT Alliance for Research and Technology (SMART) Innovation Centre (ING-000772 BIO IGN) and the SMART Antimicrobial Resistance IRG, which is supported by the National Research Foundation of Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) Program.

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.

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