This study demonstrates that nearly one-third of PLWHIV attending a large urban HIV clinic in Kampala carried methicillin-resistant Staphylococcus species in their anterior nares. Although the prevalence of MRSA was relatively modest (8.9%), the overall burden of methicillin-resistant organisms was driven largely by MRCoNS colonization (23%), highlighting the importance of considering coagulase-negative staphylococci within antimicrobial resistance surveillance frameworks.

The observed MRSA prevalence is broadly consistent with reports from other settings in sub-Saharan Africa and Asia, where nasal carriage among PLWHIV has ranged between approximately 2% and 12% (9-10, 12, 14-17). A study conducted in Ghana at a teaching hospital in 2018 reported an MRSA nasal colonization prevalence of 8.2% (9), and in a cross-sectional study in China, the prevalence of nasal carriage of MRSA among PLWHIV was 11.95% (14). Our study’s findings were higher than the 2.4% reported in Ethiopia (15), 3.4% in Taiwan (16), and 5.02% in a tertiary health facility in Buikwe district, Uganda (12), but lower than those reported in Ethiopia at 16.8% and 28% (17, 10). These differences across settings may be influenced by variations in population characteristics, sampling locations, specimen types, and techniques for bacterial isolation and identification.

Our study noted a higher prevalence of MRCoNS colonization. MRCoNS is a source of the mecA gene, which confers methicillin resistance and has the potential to contribute to the emergence of MRSA by transferring the mecA gene from MRCoNS to methicillin-susceptible S. aureus (MSSA) (2). Independently, MRCoNS colonization predisposes to infections such as bloodstream infections, endocarditis, urinary tract infections, surgical site infections, and prosthetic joint infections, particularly in immunocompromised patients, the elderly, critically ill individuals, and those with inserted foreign bodies like catheters (18). Our findings align with a study among 1001 HIV-infected patients in a tertiary facility at Guangzhou, China, which reported 11.89% MRSA and 34.45% MRCoNS prevalence (14). That study also noted multidrug resistance, with MRCoNS isolates showing 81.94% resistance compared to 18.06% for MRSA. Increasing recognition of MRCoNS as both opportunistic pathogens and sources of resistance gene transfer suggests that their epidemiology deserves greater attention in immunocompromised populations.

Frequent healthcare contact (moderate (3–4) or high (≥5) hospital visits within a year of enrollment) emerged as an important predictor of colonization (IRR = 1.18 × 10⁷, p < 0.001). Individuals reporting multiple clinic visits had a substantially higher risk of MRS carriage, consistent with evidence linking repeated healthcare exposure to colonization with antimicrobial-resistant organisms (6,19). HIV programs increasingly utilizing differentiated service delivery models, such as community-based care, could decrease healthcare exposure and MRS colonization among PLWHIV. Strengthening infection prevention practices within outpatient HIV clinics may therefore represent an important component of antimicrobial resistance control.

We also observed that individuals receiving second-line antiretroviral therapy had an increased risk of MRS colonization (IRR = 3.82, p = 0.041). This association may reflect a subgroup of patients with more complex clinical histories, including prolonged healthcare exposure, treatment failure, or greater antibiotic exposure. Similarly, unsuppressed HIV viral load was associated with MRSA colonization (AOR = 11.3; 95% CI: 2.11–60.58, p = 0.005), consistent with findings from a tertiary hospital in Ethiopia linking MRSA colonization to viral loads >1000 copies/mL (10) and another study among children and adolescents also concluded that higher viral loads increased MRSA risk compared to viral loads <1000 copies/mL (20). These findings suggest that immunologic vulnerability may contribute to susceptibility to resistant bacterial colonization.

Interestingly, self-reported mask use in clinic settings was associated with lower MRCoNS colonization. While this finding should be interpreted cautiously due to potential behavioral confounding and self-report bias, it raises the possibility that routine infection prevention practices introduced during the COVID-19 pandemic may have broader benefits for limiting bacterial transmission within healthcare environments.

The high levels of resistance observed to commonly used antibiotics, including erythromycin, ciprofloxacin, and trimethoprim-sulfamethoxazole, are concerning. Our documented cotrimoxazole resistance prevalence of 79.3% was consistent with previous findings from two systematic reviews (21,22). Given the widespread use of cotrimoxazole prophylaxis among PLWHIV in many settings (95.3% of PLWHIV in our study reported prior use), selective pressure for resistant organisms may contribute to this pattern. Continued surveillance of antimicrobial susceptibility patterns in HIV care populations is therefore essential.

This study has several limitations. First, the cross-sectional design precludes causal inference regarding risk factors for colonization. Second, laboratory identification of methicillin resistance relied on phenotypic methods without molecular confirmation. Finally, data were obtained from a single urban referral centre and may not be generalizable to other settings.

Despite these limitations, our findings highlight the substantial burden of methicillin-resistant Staphylococcus colonization among PLWHIV in an urban African setting. Integrating antimicrobial resistance surveillance within HIV care programs, strengthening infection prevention measures, and promoting antimicrobial stewardship may help mitigate the risk of colonization and subsequent infection.