Available online 3 September 2022, 106669

Mycobacterium abscessus complex is β-lactam-resistant as it produces β-lactamases.

Relebactam or nacubactam combined with β-lactams decreases the β-lactam-resistance.

There was no difference in the combinational effects between the subspecies.

Rough morphotypes are less susceptible to the antibiotics than smooth morphotypes.

: Mycobacterium abscessus complex (MABC) pulmonary disease is notoriously difficult to treat due to intrinsic resistance to many common antibiotics. MABC is β-lactam-resistant as it produces class A β-lactamases, such as blaMab, which are inhibited by diazabicyclooctane (DBO) β-lactamase inhibitors.

: To investigate the microbiological effects of the combination of β-lactam and DBO β-lactamase inhibitors (relebactam and nacubactam) against MABC and determine if the effects are associated with the MABC subspecies and colony morphotypes.

: We evaluated the antimicrobial susceptibility of three type strains and 20 clinical isolates of MABC to the combination of seven β-lactams with relebactam or nacubactam by broth microdilution checkerboard assays. For these strains, we assessed blaMab expression levels by quantitative real-time polymerase chain reaction and the genotypic diversity by 18-locus variable number tandem repeat assay.

: Relebactam and nacubactam lowered the minimum inhibitory concentrations of β-lactams, especially imipenem, meropenem, tebipenem, against MABC. There was no difference in efficacy of combination treatment between three subspecies, but rough morphotypes tended to be less susceptible than smooth morphotypes. There were no differences in blaMab expression levels and genotypic diversity between the morphotypes.

: The combination of β-lactam with relebactam or nacubactam improved the efficacy of β-lactams against all MABC subspecies, but higher concentrations of β-lactams are needed for rough morphotypes.

Mycobacterium abscessus complex

β-lactamase

diazabicyclooctane β-lactamase inhibitor

β-lactam

colony morphotype

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