Cutaneous Staphylococcus aureus Infections in Renal Edema Across Kidney Disease and the Intensive Care Unit: Pathophysiological Mechanisms, Clinical Implications, and Therapeutic Challenges.

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), remains a leading cause of skin and soft tissue infections (SSTIs) worldwide. Patients with renal edema, including those with nephrotic syndrome and chronic kidney disease (CKD), and critical illness, are particularly susceptible because of barrier dysfunction, immune impairment, and altered antimicrobial pharmacokinetics. This narrative review examines the mechanisms linking renal edema to increased susceptibility to cutaneous S. aureus infection and discusses their diagnostic and therapeutic implications. Three interconnected pathophysiological pathways appear central to this susceptibility: disruption of the cutaneous barrier, nephrotic and uremic immune dysfunction, and impaired lymphatic immune surveillance. These abnormalities facilitate bacterial colonization, and invasion, while S. aureus further exploits the renal host through adhesins, toxins, biofilm formation, and immune-evasion mechanisms. The review also highlights the challenges of managing severe staphylococcal infections in patients with kidney disease and critical illness, where augmented renal clearance, expanded volume of distribution, extracorporeal renal support, and fluctuating renal function may substantially influence antimicrobial exposure. Current management requires early recognition, source control, individualized antimicrobial selection, renal-adapted dosing, therapeutic drug monitoring, and antimicrobial stewardship. Although emerging anti-virulence and immunomodulatory strategies show promise, most remain at the preclinical or early translational stage. Overall, renal edema should be regarded as a biologically active modifier of host-pathogen interactions that contributes to increased susceptibility to cutaneous S. aureus infection across the spectrum of kidney disease.