OBJECTIVES: This study aims to investigate whether Staphylococcus aureus nasal carriage influences susceptibility to community-acquired S. aureus-associated infection and any other bacterial infection risk in healthy individuals. METHODS: This prospective cohort study included blood donors aged 18-70 years between 2014 and 2021 in Denmark. A nasal swab cultivated for S. aureus defined carriage type (exposure) and infection endpoints were redeemed antibacterial prescriptions or International Classification of Diseases, tenth revision diagnoses from national registers. Adjusted incidence rate ratio (IRR) was estimated using Poisson regression for prescriptions, while Cox regression estimated hazard ratio for diagnoses. RESULTS: Of 8738 included participants, 3503 (40.5%) were carriers. During a median follow-up of 3.8 years (interquartile range, 2.4-5.1), 1110 participants redeemed dicloxacillin/flucloxacillin and 1412 redeemed topical fusidic acid prescriptions, whereas 378 participants received hospital treatment for infections during 3.4 years (interquartile range, 1.9-4.6). Nasal carriers redeemed dicloxacillin and topical fusidic acid prescriptions more often than non-carriers (IRR, 1.40 [95% CI, 1.24-1.58] and IRR, 1.22 [1.10-1.36]
respectively). Participants who redeemed one dicloxacillin prescription were six times more likely to redeem another within 2 years. Among these, carriers had a higher incidence of redeeming additional dicloxacillin prescriptions than non-carriers (absolute risk, 19.0% vs. 12.9%, respectively
IRR 1.46 [1.17-1.84]). S. aureus nasal carriage was not associated with a higher risk of redeeming other antibacterial prescriptions nor with risk of hospital-treated S. aureus and any other bacterial infections. DISCUSSION: In this study comprising healthy adults, nasal carriers with S. aureus exhibited an increased risk of redeemed dicloxacillin and topical fusidic acid prescriptions, but nasal carriage was not associated with any other types of bacterial infection. Findings suggest that nasal carriage elevates the burden of community-acquired S. aureus infections.