Identification of novel antimicrobial drug combinations with synergistic activity against Mycobacterium abscessus
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Mycobacterium abscessus (Mab), classified as a rapid-growing mycobacterium, is naturally resistant to many antimicrobial drugs. Mab infections are typically treated with multidrug therapy, given low efficacy and risk of resistance development with monotherapy. Utilizing effective combinations of antimicrobial drugs with synergistic activity from the early stages of treatment may improve treatment success rates. We conducted a literature search of PubMed to identify studies published between 1992 and 2024 that assessed in vitro antimicrobial drug interactions in Mab. In addition, we evaluated in vitro drug interactions of 15 antimicrobial drugs that are clinically used in Japan. We utilized the diagonal measurement of n-way drug interactions (DiaMOND), a recently developed method to efficiently assess antimicrobial drug interactions. We experimentally identified 17 novel synergistic antimicrobial drug combinations against the standard Mab strain ATCC 19977. However, according to our literature review, only some synergistic interactions were conserved across different Mab strains. Combining a literature review and an in vitro assay, this study presents the most updated landscape of the activity of antimicrobial combinations against Mab.
