Evaluation of β-lactam monotherapy and conventional anti-staphylococcal combination therapy for polymicrobial MSSA infections

INTRODUCTION: Staphylococcus aureus (SA) remains a major pathogen in both community-acquired and healthcare-associated infections, necessitating effective treatment strategies. Management of infections involving methicillin-susceptible S. aureus (MSSA) has traditionally included the use of targeted anti-staphylococcal antibiotics in combination with broad-spectrum agents. Recent evidence suggests that beta-lactam antibiotics may provide equivalent or superior outcomes in MSSA infections, challenging conventional treatment paradigms. METHODOLOGY: This retrospective cohort study evaluated adult patients with polymicrobial infections involving MSSA across multiple healthcare facilities from January 2019 to December 2023. Patients receiving beta-lactam monotherapy were compared with those receiving beta-lactam therapy plus a traditional anti-staphylococcal agent. Primary outcomes included treatment failure, defined as recurrence or escalation of infection within 90 days. Secondary outcomes were 90-day hospital readmission rates and all-cause mortality. RESULTS: Of 1,000 patient records reviewed, 108 met the inclusion criteria. Beta-lactam monotherapy was associated with a significantly lower treatment failure rate compared with combination therapy (1.6% vs. 17.0%, p = 0.035). Hospital readmission rates (24.6% vs. 51.1%, p = 0.093) and all-cause mortality (11.5% vs. 19.1%, p = 0.784) were lower in the beta-lactam group, though the differences were not statistically significant. CONCLUSIONS: Beta-lactam monotherapy demonstrated comparable or superior efficacy to traditional anti-staphylococcal combination regimens for polymicrobial infections with MSSA. These findings support the potential for simplifying treatment regimens, reducing unnecessary antibiotic exposure, and enhancing antibiotic stewardship. Further prospective studies are needed to confirm these results and inform clinical practice guidelines.