In Vivo Emergence of Oxacillin Resistance in mecA ‐Negative MSSA Endocarditis With Metastatic Infection

ABSTRACT Staphylococcus aureus bacteremia (SAB) is particularly challenging when complicated by infective endocarditis (IE), metastatic spread, or evolving antimicrobial resistance. We describe a 76‐year‐old woman with poorly‐controlled diabetes who presented with bilateral knee septic arthritis and persistent methicillin‐sensitive S. aureus (MSSA) bacteremia complicated by in vivo emergence of oxacillin resistance despite a mecA‐negative genotype. Her clinical course was marked by an aortomitral intervalvular fibrosa abscess, vertebral osteomyelitis with epidural extension, a psoas abscess, and septic renal infarctions. She experienced breakthrough bacteremia despite initial clearance on oxacillin. Surgery was delayed due to intracranial hemorrhage but was ultimately enabled by middle meningeal artery embolization (MMAE). This case highlights the rare emergence of phenotypic oxacillin resistance in mecA‐negative MSSA during therapy and illustrates the role of MMAE in facilitating time‐sensitive cardiac surgery in the setting of recent intracranial bleeding. It underscores the importance of dynamic diagnostic reassessment, serial susceptibility testing, and multidisciplinary coordination in complicated SAB.