Drug Repurposing for the Treatment of Mycobacterium abscessus Infections

Résumé fourni par la source

Abstract With the ever-increasing burden of antimicrobial resistance, the demand to introduce countermeasures becomes increasingly critical. The urgency of this need is intensified by the void in antibiotic discovery, with the identification of novel compounds declining with time. Of increasing concern is Mycobacterium abscessus, which displays high levels of intrinsic resistance that lead to poor success rates, even after lengthy drug regimens. Research tackling these issues is now focused on the repurposing of preexisting drugs for antimycobacterial use, facilitating the discovery of antimicrobial compounds amidst a crisis where novel antibiotics are sparse. Part of this includes the use of combination treatments, whereby coadministration of synergistic compounds can reduce dose requirements and slow the progression of antimicrobial resistance in the long term. In this review, we will introduce the current therapeutic options for M. abscessus and provide insight into why treatment is so burdensome. We will also compile the current updates within drug repurposing for this pathogen, including the use of unconventional agents such as antimalarial drugs, the repositioning of antituberculosis candidates and the repurposing of preexisting antibiotics, including the application of combination regimens. In addition, the in vitro drug screening platforms used in their discovery will be appraised, with the view of highlighting potential future perspectives that may help increase physiological relevance. This review provides a timely appraisal of the future of M. abscessus treatment.

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