Our understanding of how antimicrobial resistance enzymes evolve to expand their substrate spectrum is limited. OXA-48, an enzyme able to catalyse the hydrolysis of β-lactam drugs, has become one of the most successfully disseminating β-lactamases. Although OXA-48 hydrolyses penicillins with high efficiency, its activity towards oxyimino cephalosporins, such as ceftazidime, is limited. Thus, ceftazidime ...