Management of methicillin-resistant Staphylococcus aureus bloodstream infections: a comprehensive narrative review of available evidence focusing on current controversies and the challenges ahead

Introduction: Bloodstream infections (BSIs) caused by Staphylococcus aureus are common worldwide, representing one of the most relevant issues in clinical infectious diseases practice. In particular, BSIs by methicillin-resistant S. aureus (MRSA-BSI) are still today a challenge since mortality burden remains elevated although decades of research. Areas covered: The following topics regarding MRSA-BSI were reviewed and discussed by resorting to best available evidence retrieved from PubMed/MEDLINE up to October 2024: i) epidemiology; ii) microbiology; iii) classification, with a focus on complicated and not complicated forms; iv) the structured approach to the patient; v) pharmacokinetics and pharmacodynamics of the main antimicrobial options; vi) controversies regarding the best therapeutic approach. Expert opinion: Despite ongoing efforts to better stratify and manage MRSA-BSI, there is no universally accepted classification system accurately distinguishing between uncomplicated/low risk and complicated/high risk forms. Biomarkers such as interleukin(IL)-10 hold promise in order to enable a more precise stratification, premise for an appropriate treatment plan. There is a theoretical rationale for implementing a combination therapy including a beta-lactam agent upfront, especially for patients considered at higher risk of unfavorable outcomes, but further data are necessary, and the same applies to newer adjuvants. Novel microbiological techniques may help in guiding antimicrobial duration.