Antibiotic synergy against : a systematic review and meta-analysis.

Antimicrobial combinations have been extensively evaluated to identify synergistic combinations for clinical use. Despite the available literature, no studies comprehensively summarize the findings for antimicrobial combinations against . We performed a systematic review to identify synergistic combinations that may be beneficial for clinical use against . The PubMed, Cochrane, and Web of Science databases were queried from inception to February 2024 for studies of assays evaluating two antimicrobials in combination against isolates of . Studies were included if they used common methods to determine synergy including time-kill assays, checkerboard assays, or the combined gradient diffusion method. The proportion of isolates for which synergy was identified was compared for different antimicrobial combinations. Two hundred sixty-five studies were included for analysis. One hundred forty-two studies evaluated synergy against methicillin-resistant (MRSA), 31 against methicillin-susceptible (MSSA), and 92 assessed synergy against both MRSA and MSSA, or did not define the methicillin susceptibility profile of the isolates studied. Time-kill assays ( = 176) and checkerboard assays ( = 158) were the most frequently used methods, with few studies evaluating synergy using the combined gradient diffusion method ( = 13). The proportion of synergy varied based on the antimicrobial combination and isolate being evaluated. Antimicrobial synergy has been extensively studied for , with combinations of glycopeptides and cephalosporins being studied most frequently. Future evaluations of synergy for should focus on antimicrobial combinations with strong rationales and robust potential for clinical use.