Importance  Previous studies suggested that a bundled intervention was associated with lower rates ofStaphylococcus aureus surgical site infections (SSIs) among patients having cardiac or orthopedic operations.
Objective  To evaluate whether the implementation of an evidence-based bundle is associated with a lower risk of S aureus SSIs in patients undergoing cardiac operations or hip or knee arthroplasties.
Design, Setting, and Participants  Twenty hospitals in 9 US states participated in this pragmatic study; rates of SSIs were collected for a median of 39 months (range, 39-43) during the preintervention period (March 1, 2009, to intervention) and a median of 21 months (range, 14-22) during the intervention period (from intervention start through March 31, 2014).
Interventions  Patients whose preoperative nares screens were positive for methicillin-resistant S aureus(MRSA) or methicillin-susceptible S aureus (MSSA) were asked to apply mupirocin intranasally twice daily for up to 5 days and to bathe daily with chlorhexidine-gluconate (CHG) for up to 5 days before their operations. MRSA carriers received vancomycin and cefazolin or cefuroxime for perioperative prophylaxis; all others received cefazolin or cefuroxime. Patients who were MRSA-negative and MSSA-negative bathed with CHG the night before and morning of their operations. Patients were treated as MRSA-positive if screening results were unknown.
Main Outcomes and Measures  The primary outcome was complex (deep incisional or organ space) S aureus SSIs. Monthly SSI counts were analyzed using Poisson regression analysis.
Results  After a 3-month phase-in period, bundle adherence was 83% (39% full adherence; 44% partial adherence). Overall, 101 complex S aureus SSIs occurred after 28 218 operations during the preintervention period and 29 occurred after 14 316 operations during the intervention period (mean rate per 10 000 operations, 36 for preintervention period vs 21 for intervention period, difference, −15 [95% CI, −35 to −2]; rate ratio [RR], 0.58 [95% CI, 0.37 to 0.92]). The rates of complex S aureus SSIs decreased for hip or knee arthroplasties (difference per 10 000 operations, −17 [95% CI, −39 to 0]; RR, 0.48 [95% CI, 0.29 to 0.80]) and for cardiac operations (difference per 10 000 operations, −6 [95% CI, −48 to 8]; RR, 0.86 [95% CI, 0.47 to 1.57]).
Conclusions and Relevance  In this multicenter study, a bundle comprising S aureus screening, decolonization, and targeted prophylaxis was associated with a modest, statistically significant decrease in complex S aureus SSIs.