DifferentialIn VitroActivities of Individual Drugs and Bedaquiline-Rifabutin Combinations against Actively Multiplying and Nutrient-StarvedMycobacterium abscessus

Abstract

ABSTRACTCurrent treatment options for lung disease caused byMycobacterium abscessuscomplex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed thein vitrobactericidal activity of single drugs against actively multiplying and net nonreplicatingM. abscessuspopulations in nutrient-rich and nutrient-starvation conditions, respectively. As single drugs, bedaquiline and rifabutin exerted bactericidal activity only against nutrient-starved and actively growingM. abscessus, respectively. However, when combined, both bedaquiline and rifabutin were able to specifically contribute bactericidal activity at relatively low, clinically relevant concentrations against both replicating and nonreplicating bacterial populations. The addition of a third drug, amikacin, further enhanced the bactericidal activity of the bedaquiline-rifabutin combination against nutrient-starvedM. abscessus. Overall, thesein vitrodata suggest that bedaquiline-rifabutin may be a potent backbone combination to support novel treatment regimens forM. abscessusinfections. This rich data set of differential time- and concentration-dependent activity of drugs, alone and together, againstM. abscessusalso highlights several issues affecting interpretation and translation ofin vitrofindings.