STI-driven antibiotic exposure may shape macrolide and tetracycline resistance in nasal Staphylococcus aureus among MSM receiving HIV pre-exposure prophylaxis

Background: HIV pre-exposure prophylaxis (PrEP) programmes are associated with intensified sexually transmitted infection (STI) screening and increased incidence of bacterial STIs, resulting in repeated antibiotic exposure. The ecological impact of STI-driven antimicrobial use on resistance in commensal bacteria remains insufficiently characterised, particularly in populations with high antimicrobial exposure such as men who have sex with men (MSM). Objective: To evaluate differences in nasal Staphylococcus aureus antimicrobial resistance between MSM receiving PrEP and HIV-negative MSM not on PrEP and to explore behavioural and antibiotic exposure factors associated with resistance. Methods: In this exploratory cross-sectional study, 153 HIV-negative MSM attending an STI clinic in Italy were enrolled (80 PrEP users; 73 controls). Participants underwent nasal swabbing for culture-based isolation and antimicrobial susceptibility testing of S. aureus. Antibiotic exposure, behavioural variables and STI history were collected via structured questionnaire. Results: PrEP users reported more sexual partners in the last 6 months (p=0.0009) and higher antibiotic use in the preceding year (p=0.004). Doxycycline postexposure prophylaxis (Doxy-PEP) use was more frequent among PrEP users (16% vs 7%; p=0.08). The cumulative 2-year STI burden was higher in the PrEP group (p<0.0001), driven by Neisseria gonorrhoeae infections. S. aureus colonisation prevalence did not differ significantly between groups (p=0.17). However, erythromycin (p=0.0008), clindamycin (p=0.004) and tetracycline resistance (p=0.03) were more frequent among PrEP users. Tetracycline exposure was independently associated with tetracycline resistance (p=0.03), whereas PrEP status was not. Conclusions: Among MSM, higher antimicrobial resistance in nasal S. aureus may be associated with antibiotic exposure rather than PrEP use per se. These exploratory findings should be interpreted with caution given the limited sample size and lack of detailed exposure quantification but support the need to integrate antimicrobial stewardship into PrEP and Doxy-PEP implementation frameworks. Longitudinal studies are needed to better disentangle the roles of antimicrobial exposure and transmission dynamics.