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

Background and objectives 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. Material and methods 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. Results 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. Conclusion 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.