Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug 
resistance and the persistence of drug-tolerant bacteria. Currently, the 
standard of care is a multidrug regimen with at least 3 active drugs, preferably 
including a β-lactam (imipenem or cefoxitin). These regimens are lengthy and 
toxic and have limited efficacy. The search for more efficacious regimens led us 
to evaluate bedaquiline, a diarylquinoline licensed for treatment of 
multidrug-resistant tuberculosis. We performed in vitro time-kill experiments to 
evaluate the activity of bedaquiline alone and in combination with the 
first-line drug imipenem against M. abscessus under various conditions. Against 
actively growing bacteria, bedaquiline was largely bacteriostatic and 
antagonized the bactericidal activity of imipenem. Contrarily, against 
nutrient-starved persisters, bedaquiline was bactericidal, while imipenem was 
not, and bedaquiline drove the activity of the combination. In an intracellular 
infection model, bedaquiline and imipenem had additive bactericidal effects. 
Correlations between ATP levels and the bactericidal activity of imipenem and 
its antagonism by bedaquiline were observed. Interestingly, the presence of 
Tween 80 in the media affected the activity of both drugs, enhancing the 
activity of imipenem and reducing that of bedaquiline. Overall, these results 
show that bedaquiline and imipenem interact differently depending on culture 
conditions. Previously reported antagonistic effects of bedaquiline on imipenem 
were limited to conditions with actively multiplying bacteria and/or the 
presence of Tween 80, whereas the combination was additive or indifferent 
against nutrient-starved and intracellular M. abscessus, where promising 
bactericidal activity of the combination suggests it may have a role in future 
treatment regimens.