Antimicrobial susceptibility of Mycobacterium abscessus and treatment of pulmonary and extra-pulmonary infections

BackgroundMycobacterium abscessus (MAB) is the mycobacterial species the least susceptible to antimicrobials. Infections are difficult to treat and cure rates are below 50% even after a combination of 4-5 drugs for many months.ObjectivesTo examine antimicrobial susceptibilities and treatment recommendations in light of what is known about mechanisms of resistance and pharmacodynamics/pharmacokinetics (PK/PD) interactions.SourcesOriginal papers on the topics of “antimicrobials”, “susceptibility”, “treatment”, “outcome” from 2019 onwards, in the context of the evidence brought by the guidelines published in 2020 for pulmonary infections.ContentMAB is susceptible in vitro to only a few antimicrobials. Breakpoints were set by CLSI and are revised by EUCAST for epidemiological cutoff values. Innate resistance is due to multiple resistance mechanisms involving efflux pumps, inactivating enzymes, and low drug-target affinity. In addition, MAB may display acquired resistance to macrolides and amikacin through mutations in drug binding sites. Treatment outcomes are better for macrolide-based combinations and MAB subspecies massiliense. New compounds in the family of cyclines, oxazolidinones, and penem-beta-lactamase inhibitor combinations (described in another paper), as well as bedaquiline, a new antituberculous agent, are promising, but their efficacy remains to be proven. Pharmacokinetic/pharmacodynamics (PK/PD) studies, which are critical for establishing optimal dosing regimens, were mainly done for monotherapy and healthy individuals.ImplicationsMedical evidence is poor and randomized clinical trials or standardized cohorts are needed to compare outcomes of patients with similar underlying disease, clinical characteristics and identified MAB subspecies/sequevar. Microbiological diagnosis and susceptibility testing need to be harmonized for enabling to compare agents and test new compounds. Testing antimicrobial combinations require new methods, especially for PK/PD parameters. Molecular testing may help in assessing MAB resistance prior to treatment. New antimicrobials need to be systematically tested against MAB to find an effective antimicrobial regimen.