BACKGROUND: Infections with Staphylococcus aureus (S. aureus) are associated with excess mortality and costs. Simple interventions, such as decolonization protocols, might help to reduce subsequent infections, especially in settings in which S. aureus is of major clinical relevance, such as healthcare-associated infections. AIM: To determine if S. aureus decolonization protocols, using a nasal ointment and applied at hospital admission, reduce the risk of infection. SEARCH METHODS: MEDLINE, EMBASE and clinicaltrials.gov were searched for all randomized controlled trials investigating the use of nasal ointments for decolonization for patients at hospital admission and reporting on infections within 90 days. Data were pooled as risk ratios using a random-effects model. The Cochrane RoB 2 tool and GRADE were used to assess the risk of bias and quality of evidence. RESULTS: Four (0.5%) of 833 screened studies with a total of 4,150 patients met eligibility criteria. The overall certainty of evidence ranged from low to moderate across outcomes. Nasal S. aureus decolonization likely reduces infections (6.9% vs. 9.5%
rate ratio (RR): 0.73 (95%CI 0.57
0.93)) and may increase microbiological eradication (82.7% vs. 55.2%
RR: 1.80 (95%CI 0.73
4.44) compared to placebo. It may not reduce mortality (2.5 vs. 2.4
RR: 1.02 (95%CI 0.67
1.54) but also not lead to increased adverse effects (0.7% vs 0.6%
RR: 1.01, 95% CI 0.45
2.30). Results were consistent across subgroups and sensitivity analyses.