Case Commentary: The hidden side of oxacillin resistance in .

Acquisition of PBP2a (encoded by the gene) is the key resistance mechanism to β-lactams in . The gene can be easily detected by PCR assays; however, these tools will miss 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 c-independent oxacillin resistance.