TY - JOUR
T1 - Differential in vitro activities of individual drugs and bedaquiline-rifabutin combinations against actively multiplying and nutrient-starved mycobacterium abscessus
AU - Lee, Jin
AU - Ammerman, Nicole
AU - Agarwal, Anusha
AU - Naji, Maram
AU - Li, Si Yang
AU - Nuermberger, Eric
N1 - Publisher Copyright:
Copyright © 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Current treatment options for lung disease caused by Mycobacterium abscessus complex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed the in vitro bactericidal activity of single drugs against actively multiplying and net nonreplicating M. abscessus populations in nutrient-rich and nutrient-starvation conditions, respectively. As single drugs, bedaquiline and rifabutin exerted bactericidal activity only against nutrient-starved and actively growing M. 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-starved M. abscessus. Overall, these in vitro data suggest that bedaquiline-rifabutin may be a potent backbone combination to support novel treatment regimens for M. abscessus infections. This rich data set of differential time- and concentration-dependent activity of drugs, alone and together, against M. abscessus also highlights several issues affecting interpretation and translation of in vitro findings.
AB - Current treatment options for lung disease caused by Mycobacterium abscessus complex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed the in vitro bactericidal activity of single drugs against actively multiplying and net nonreplicating M. abscessus populations in nutrient-rich and nutrient-starvation conditions, respectively. As single drugs, bedaquiline and rifabutin exerted bactericidal activity only against nutrient-starved and actively growing M. 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-starved M. abscessus. Overall, these in vitro data suggest that bedaquiline-rifabutin may be a potent backbone combination to support novel treatment regimens for M. abscessus infections. This rich data set of differential time- and concentration-dependent activity of drugs, alone and together, against M. abscessus also highlights several issues affecting interpretation and translation of in vitro findings.
KW - Amikacin
KW - Bedaquiline
KW - Mycobacterium abscessus
KW - Nontuberculous mycobacteria
KW - Rifabutin
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U2 - 10.1128/AAC.02179-20
DO - 10.1128/AAC.02179-20
M3 - Article
C2 - 33168614
AN - SCOPUS:85099934737
SN - 0066-4804
VL - 65
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 2
M1 - e02179-20
ER -