# In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates

## TL;DR

This study shows that combining sulbactam/durlobactam with beta-lactam antibiotics improves their effectiveness against Mycobacterium abscessus in laboratory tests.

## Contribution

The novel finding is that sulbactam/durlobactam enhances the efficacy of meropenem, cefuroxime, and cefuroxime/amoxicillin against M. abscessus.

## Key findings

- Sulbactam/durlobactam reduced MICs of meropenem, cefuroxime, and cefuroxime/amoxicillin to levels comparable to imipenem.
- Culture medium significantly affected MIC results, with Middlebrook 7H9 showing lower MICs than CLSI CAMHB media for durlobactam combinations.

## Abstract

Mycobacterium abscessus has extensive innate and acquired antibiotic resistance resulting in limited antibiotic treatment options and poor clinical outcomes. Currently, the only β-lactam antibiotics with efficacy against M. abscessus are imipenem and cefoxitin. Durlobactam is a β-lactamase inhibitor that may overcome intrinsic resistance mechanisms and enable the use of alternative oral β-lactam antibiotics. The objective of this study was to determine whether sulbactam/durlobactam increases the susceptibility of M. abscessus to alternative β-lactam antibiotics.

Antibiotic susceptibility testing was performed for durlobactam, meropenem, cefuroxime/amoxicillin alone, and sulbactam/durlobactam alone and in combination with meropenem and cefuroxime/amoxicillin according to Clinical Laboratory Standards Institute (CLSI) standards. These results were then compared with imipenem susceptibility with and without relebactam.

Sulbactam/durlobactam significantly lowered the MICs of M. abscessus to meropenem, cefuroxime and cefuroxime/amoxicillin to MICs comparable to those of imipenem and imipenem/relebactam. The culture medium used had a significant impact on MIC, with Middlebrook 7H9 having significantly lower MICs for all combinations containing durlobactam compared with CLSI standard CAMHB media.

Sulbactam/durlobactam significantly increased susceptibility to oral and intravenous β-lactam antibiotics in the form of cefuroxime, cefuroxime/amoxicillin and meropenem against clinical isolates of M. abscessus. This study also found significant differences in susceptibility to β-lactam antibiotics dependent on the culture media used, highlighting that the optimal culture methods for determining MIC in M. abscessus remains uncertain. Future in vivo studies are required to determine whether the in vitro efficacy of the β-lactam combinations studied could result in clinical efficacy for M. abscessus disease.