Unveiling the spectrum of vancomycin resistance in Staphylococcus aureus from Hospital-acquired urinary tract infections (HA-UTI) in cardiac patients.

BACKGROUND: Patients with cardiac disease are highly susceptible to hospital-acquired urinary tract infections (HA-UTI) due to immunosuppression, invasive procedures, and prolonged hospitalization. Although Enterobacteriaceae are frequent pathogens, the contribution of vancomycin-resistant Staphylococcus aureus (VRSA) remains unexplored. Among 11 known glycopeptide resistance genes (vanA, vanB, vanD, vanF, vanI, vanM, vanC, vanE, vanG, vanL, and vanN), vanA and vanB are most commonly reported. However, the diversity of other van genes and their interplay with antimicrobial resistance (AMR) and virulence determinants are poorly characterized.

METHODS AND RESULTS: Between March 2020 and April 2022, 189 cardiac ward patients were screened for VRSA-associated HA-UTI. The presence of van genes, efflux pump genes (norA, norB, sepA, mepA, mdeA), and virulence genes (hla, sea, icaA, fnbA) was determined using singleplex PCR, correlation analysis, and qRT-PCR for expression profiling. Antimicrobial susceptibility was assessed via disk diffusion, minimum inhibitory concentration (MIC), hierarchical clustering, and multiple antibiotic resistance indexing. 55% of VRSA isolates harboured limited van gene diversity, with vanA predominant. These isolates exhibited extensive AMR, high vancomycin MICs (> 256 µg/mL), and multidrug resistance. Co-occurrence of efflux pump genes (norA + norB, norB + norC, sepA + norB) and virulence genes (hla + sea, icaA + fnbA) showed significant positive correlations. All isolates were susceptible to linezolid and chloramphenicol.

CONCLUSION: vanA-mediated resistance in VRSA from HA-UTI is strongly associated with efflux pump activity and virulence gene expression. Integrative genomic and transcriptomic approaches are essential for deciphering these networks, guiding precision therapeutics, and strengthening infection control measures.