Sulbactam-durlobactam susceptibility among cefiderocol heteroresistant Acinetobacter

ABSTRACT The ATTACK clinical trial for treatment of carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) isolates determined treatment with sulbactam-durlobactam to be efficacious and safe. However, other newly introduced β-lactam antibiotics, including the novel cephalosporin cefiderocol, have been compromised upon clinical introduction by a type of antibiotic resistance called heteroresistance, in which only a small subpopulation of total cells exhibit phenotypic resistance. Therefore, we sought to test for sulbactam-durlobactam heteroresistance, as well as whether sulbactam-durlobactam was effective against cefiderocol heteroresistant CRAB isolates. We did not observe heteroresistance (or conventional resistance) to sulbactam-durlobactam among the 107 carbapenem-resistant Acinetobacter isolates tested, consistent with the efficacy of this new antibiotic in the ATTACK trial. Further, sulbactam-durlobactam was active against cefiderocol heteroresistant CRAB, highlighting that this antibiotic may be prioritized in relation to cefiderocol in treating CRAB infections.