Rethinking Preoperative MRSA/MSSA Screening Through Molecular Triage

Background: Preoperative screening for methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) is intended to identify patients at increased risk of surgical site infection and guide decolonization and perioperative antimicrobial prophylaxis. However, many molecular assays reduce this decision to a binary positive/negative result, potentially obscuring clinically important distinctions in organism identity, methicillin resistance attribution, and mupirocin resistance risk. Methods: This structured narrative review organized direct perioperative evidence and indirect mechanistic, implementation, and economic evidence around one question: how MRSA/MSSA screening can move from organism detection to actionable molecular triage. Results: Useful preoperative reporting depends on assigning resistance markers to the correct organism. The proposed multi-target NAAT framework organizes concordant and discordant molecular patterns into provisional reportable categories, including MSSA, MRSA, methicillin-resistant non-aureus Staphylococcus/CoNS, mixed populations, SCCmec dropout patterns, mupirocin resistance marker states, and invalid or indeterminate results. No externally validated composite score, universal molecular cutoff, or prospectively validated target-to-action decision rule currently links all of these categories to specific perioperative actions. Conclusions: Preoperative MRSA/MSSA screening may benefit from moving beyond binary reporting, but the framework presented here is a development-stage rule set rather than a validated clinical decision instrument. Assay-specific analytical thresholds, locked target combination rules, and prospective clinical and implementation validation are required before the framework can be used to assign patients reproducibly to management pathways. Until such validation is completed, the proposed categories should be interpreted as a testable reporting and validation architecture rather than as universal prophylaxis or decolonization instructions.