Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococci (VRE) in Nosocomial Infections: A Systematic Review of Resistance, Pathogenesis, and Clinical Management

Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are high-burden healthcare-associated pathogens that increase mortality, prolong hospitalisation, and drive substantial healthcare costs worldwide. These infections are associated with high morbidity, increased mortality, prolonged hospital stays, and significant costs, particularly among immunocompromised patients or those with extended hospitalizations. This systematic review was conducted and reported in accordance with PRISMA 2020, aiming to synthesise existing data on the epidemiology, resistance mechanisms, clinical manifestations, and strategies for the diagnosis, treatment, and prevention of MRSA and VRE infections. Data were qualitatively synthesised. A total of 113 records published between 2020 and 2025 met the inclusion criteria and were identified through searches in multiple bibliographic databases and publisher platforms (e.g., PubMed, Scopus, Web of Science). MRSA and VRE are implicated in numerous severe infections, including ventilator-associated pneumonia, catheter-associated urinary tract infections, endocarditis, and bacteraemia. Antimicrobial resistance is driven by the mecA, vanA, and vanB genes, while biofilm formation further complicates therapeutic efforts. Biofilm formation can promote antibiotic tolerance (slower killing without an increase in MIC) and persistence (survival of ‘persister’ cells), distinct from genetic resistance, and may complicate therapy in selected infections. Effective strategies include appropriate anti-MRSA/anti-VRE agents (e.g., ceftaroline for MRSA; linezolid or daptomycin for VRE), active screening, stringent infection prevention and control measures, and antimicrobial stewardship programmes. Implementation is often hindered by institutional barriers, limited resources, and insufficient staff training. A multidisciplinary, evidence-based approach is essential for the effective management of these infections. Reducing this burden requires coordinated implementation of rapid diagnostics, stringent infection prevention and control, and antimicrobial stewardship, supported by sustained institutional and public health investment.