Since its initial description in the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has developed multiple mechanisms for antimicrobial resistance and evading the immune system, including biofilm production. MRSA is now a widespread pathogen, causing a spectrum of infections ranging from superficial skin issues to severe conditions like osteoarticular infections and endocarditis, leading to high morbidity and mortality. Biofilm production is a key aspect of MRSA’s ability to invade, spread, and resist antimicrobial treatments. Environmental factors, such as suboptimal antibiotics, pH, temperature, and tissue oxygen levels, enhance biofilm formation. Biofilms are intricate bacterial structures with dense organisms embedded in polysaccharides, promoting their resilience. The process involves stages of attachment, expansion, maturation, and eventually disassembly or dispersion. MRSA’s biofilm formation has a complex molecular foundation, involving genes like icaADBC, fnbA, fnbB, clfA, clfB, atl, agr, sarA, sarZ, sigB, sarX, psm, icaR, and srtA. Recognizing pivotal genes for biofilm formation has led to potential therapeutic strategies targeting elemental and enzymatic properties to combat MRSA biofilms. This review provides a practical approach for healthcare practitioners, addressing biofilm pathogenesis, disease spectrum, and management guidelines, including advances in treatment. Effective management involves appropriate antimicrobial therapy, surgical interventions, foreign body removal, and robust infection control practices to curtail spread within healthcare environments.

Infective endocarditis (IE) is a life-threatening condition with increasing global incidence, primarily caused by Staphylococcus aureus, especially methicillin-resistant strains (MRSA). Biofilm formation by S. aureus is a critical factor in pathogenesis, contributing to antimicrobial resistance and complicating the treatment of infections involving prosthetic valves and cardiovascular devices. Biofilms provide a protective matrix for MRSA, shielding it from antibiotics and host immune defenses, leading to persistent infections and increased complications, particularly in cases involving prosthetic materials. Clinical manifestations range from acute to chronic presentations, with complications such as heart failure, embolic events, and neurological deficits. Diagnosis relies on the Modified Duke Criteria, which have been updated to incorporate modern cardiovascular interventions and advanced imaging techniques, such as PET/CT (positron emission tomography, computed tomography), to improve the detection of biofilm-associated infections. Management of MRSA-associated IE requires prolonged antimicrobial therapy, often with vancomycin or daptomycin, needing a combination of antimicrobials in the setting of prosthetic materials and frequently necessitates surgical intervention to remove infected prosthetic material or repair damaged heart valves. Anticoagulation remains controversial, with novel therapies like dabigatran showing potential benefits in reducing thrombus formation. Despite progress in treatment, biofilm-associated resistance poses ongoing challenges. Emerging therapeutic strategies, including combination antimicrobial regimens, bacteriophage therapy, antimicrobial peptides (AMPs), quorum sensing inhibitors (QSIs), hyperbaric oxygen therapy, and nanoparticle-based drug delivery systems, offer promising approaches to overcoming biofilm-related resistance and improving patient outcomes. This review provides an overview of the pathogenesis, current management guidelines, and future directions for treating biofilm-related MRSA IE.

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of serious infection and is associated with substantial morbidity and mortality. Clinical presentations range from localized disease to severe, life-threatening infections, including bacteremia and sepsis with metastatic complications such as infective endocarditis and osteoarticular involvement. MRSA bacteremia carries a high risk of dissemination and death, underscoring the importance of early recognition and effective management. Optimal treatment requires timely initiation of appropriate antimicrobial therapy in conjunction with source control when indicated. Despite advancements in treatment, persistent MRSA bacteremia continues to pose significant clinical challenges. Given the complexity of these infections, a clear understanding of current treatment strategies is essential for clinicians. In this narrative review, we summarize contemporary guideline-based approaches to the management of MRSA bacteremia, highlight key pharmacologic considerations of available antimicrobial agents, and discuss knowledge gaps and recent developments in both established and emerging therapies aimed at improving outcomes in these challenging infections.