Abstract
Mycobacterium abscessus is a non-tuberculous mycobacterium notoriously known for causing severe, chronic infections. Treatment of these infections is challenging due to either intrinsic or acquired resistance of M. abscessus to multiple antibiotics. Despite prolonged poly-antimicrobial therapy, treatment of M. abscessus infections often fails, leading to progressive morbidity and eventual mortality. Great research efforts are invested in finding new therapeutic options for M. abscessus. Clofazimine and rifabutin are known anti-mycobacterial antibiotics, repurposed for use against M. abscessus. Novel antimicrobials active against M. abscessus include delamanid, pretomanid and PIPD1 and the recently approved beta-lactamase inhibitors avibactam, relebactam and vaborbactam. Previously unused antimicrobial combinations, e.g. vancomycin–clarithromycin and dual beta-lactam therapy, have been shown to have synergistic effect against M. abscessus in experimental models, suggesting their possible use in multiple-drug regimens. Finally, engineered phage therapy has been reported to be clinically successful in a severe case of disseminated M. abscessus infection. While many of these experimental therapeutics have shown activity against M. abscessus in vitro, as well as in intracellular and/or animal models, most have little if any evidence of effect in human infections. Clinical studies of M. abscesssus treatments are needed to reliably determine the value of their incorporation in therapeutic regimens.
Highlights
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms being increasingly recognized as human pathogens, with rising incidence of infections [1]
This review summarizes evidence of novel and experimental therapeutic options for treatment of M. abscessus infections
In Mycobacterium tuberculosis, it was shown to act through inhibition of the ATP Synthase [48], which is considered true in other mycobacteria as well
Summary
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms being increasingly recognized as human pathogens, with rising incidence of infections [1]. Current treatment recommendations of M. abscessus pulmonary infections include combination therapy of two or more intravenous drugs (i.e., amikacin, tigecycline, imipenem and cefoxitin) with one or two oral antimicrobials including macrolides, linezolid, clofazimine and, occasionally, a quinolone. When treating M. abscessus isolates with inducible macrolide-resistance, practice guidelines may differ—while some recommend their use [6], others suggest using other antimicrobials as guided by susceptibility testing [1]. These differences in approach stem from the paucity of clinical data comparing the clinical effect of different treatment combinations. These include novel antibiotics, new—and sometimes counter-intuitive—antibiotic combinations, re-purposing of known antibiotics and phage therapy
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