PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam

PER-1-producing Pseudomonas and Acinetobacter and PER-2-producing Enterobacterales, respectively, are increasingly difficult to treat due to combined resistance to antibiotics like ceftazidime, cefiderocol, and ceftazidime/aztreonam-avibactam, among others. PER-14 differs from PER-2 by an S130T substitution. Through combined functional and in silico analyses, we demonstrated that PER-14 is resistant to avibactam and relebactam inhibition while retaining an extended-spectrum activity and the ability to hydrolyze cefiderocol, as the S130T substitution affects the proper binding of the DBOs.