Case Commentary: The hidden side of oxacillin resistance in Staphylococcus aureus .

Acquisition of PBP2a (encoded by the mec gene) is the key resistance mechanism to β-lactams in Staphylococcus aureus . The mec gene can be easily detected by PCR assays; however, these tools will miss me c-independent oxacillin resistance. This phenotype is mediated by mutations in cell wall metabolism genes that can be acquired during persistent infections under prolonged antibiotic exposure. The complex case presented by Hess et al. (Antimicrob Agents Chemother 67:e00437-23, 2023, https://doi.org/10.1128/aac.00437-23) highlights the diagnostic and therapeutic challenges in the management of me c-independent oxacillin resistance.