# In Vitro Susceptibility to Imipenem/Relebactam and Comparators in a Multicentre Collection of Mycobacterium abscessus Complex Isolates

## TL;DR

This study tests how well imipenem/relebactam works against Mycobacterium abscessus infections and finds it to be highly effective with potential for combination therapies.

## Contribution

The study demonstrates the in vitro efficacy of imipenem/relebactam and identifies genetic factors linked to resistance in MABc isolates.

## Key findings

- Imipenem/relebactam showed 97.6% susceptibility in MABc isolates, with only four resistant cases.
- Genetic mutations in BlaMab, transpeptidases, and mspA porin were linked to reduced susceptibility to imipenem/relebactam.
- The drug combination demonstrated synergism with other antimicrobials, supporting its use in dual regimens.

## Abstract

Background and Objectives: Infections caused by non-tuberculous mycobacteria (NTM), including Mycobacterium abscessus complex (MABc), are increasing globally and are notoriously difficult to treat due to the intrinsic resistance of these bacteria to many common antibiotics. The aims of this study were to demonstrate the in vitro activity of imipenem/relebactam against MABc clinical isolates and to determine any in vitro synergism between imipenem/relebactam and other antimicrobials. Methods: A nationwide collection of 175 MABc clinical respiratory isolates obtained from 24 hospitals in Spain (August 2022–April 2023) was studied. Fifteen different antimicrobial agents were comprised, including imipenem/relebactam. MICs were determined according to CLSI criteria, and the synergism studies were performed with the selected clinical isolates. Results: Of the 175 isolates obtained, 110 were identified as M. abscessus subsp. abscessus (62.9%), 51 as M. abscessus subsp. massiliense (29.1%), and 14 as M. abscessus subsp. bolleti (8%). The antibiotics yielding the highest susceptibility rates were tigecycline, eravacycline, and omadacycline (100%); followed by imipenem/relebactam and clofazimine (97.6%); and finally amikacin (94.6%). Only four isolates were resistant to imipenem/relebactam, three of which were further characterized by WGS, revealing MABc mutations in BlaMab as well as D,D- and L,D-transpeptidades and mspA porin, which may play an important role in reduced susceptibility to imipenem/relebactam, even though none were previously described or associated with resistance to β-lactams. Conclusions: Our data demonstrate that relebactam improved the anti-MABc activity of imipenem, representing a β-lactam for the treatment of MABc infections. Furthermore, imipenem/relebactam demonstrated in vitro synergism with other anti-MABc treatments, thus supporting its use as part of dual regimens.