OBJECTIVEPostoperative surgical site infections (SSIs) in neurosurgical patients carry a significant risk of increased morbidity and mortality. With SSIs accounting for approximately 20% of nosocomial infections and costing approximately $1.6 billion USD annually, there is a need for additional prophylaxis to improve current standards of care. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. A randomized controlled trial assessing its efficacy in the general neurosurgical population is currently underway. Here, the authors report their initial impressions of topical vancomycin safety among patients enrolled during the 1st year of the trial.METHODSThis prospective, multicenter, patient-blinded, randomized controlled trial will enroll 2632 patients over 5 years. Here, the authors report the incidence of adverse events, the degree of systemic vancomycin absorption in treated patients, and pattern changes of antibiotic-resistant profiles of Staphylococcus aureus flora among patients enrolled during the 1st year.RESULTSThe topical vancomycin treatment group comprised 257 patients (514 total enrolled patients), of whom 2 exhibited weakly positive serum levels of vancomycin (> 3.0 mg/dl). S. aureus was detected preoperatively in the anterior nares of 35 (18.1%) patients and the skin near the surgical site of 9 (4.7%). Colonization in the nares remained for many patients (71.4%) through postoperative day 30. The authors found a significant association between preoperative S. aureus colonization and postoperative colonization. Seven methicillin-resistant isolates were detected among 6 different patients. Two isolates were detected preoperatively, and 5 were de novo postoperative colonization. No adverse responses to treatment have been reported to date.CONCLUSIONSThe authors’ data indicate that the use of topical vancomycin is safe with no significant adverse effects and minimal systemic absorption, and no development of vancomycin-resistant microorganisms.Clinical trial registration no.: NCT02284126 (clinicaltrials.gov)