Effects of the Sequence of Empiric Beta-Lactam and Vancomycin Administration on Clinical Outcomes in Patients with Bloodstream Infection: A Systematic Review

<b>Background/Objectives</b>: Beta-lactam antibiotics (BLAs) and vancomycin have remained the cornerstones of therapy for serious bacterial infections, especially bloodstream infections (BSIs). The clinical impact of administering BLAs before vancomycin on outcomes remains unclear and poorly synthesized. Therefore, this systematic review aims to synthesize the available evidence on the impact of the relative timing of BLA administration to vancomycin initiation on important clinical outcomes in patients with BSIs. <b>Methods</b>: A comprehensive search was performed to retrieve clinical studies that evaluated the impact of the sequence of BLA and vancomycin administration on clinical outcomes. Beta-lactam-first group (BLF) included patients who received a BLA before vancomycin, while vancomycin-first group (VF) included patients who received vancomycin prior to BLAs. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. <b>Results</b>: A total of three retrospective observational studies were included, with a sample size of 29,005 patients, with 24,356 patients in the BLF and 4649 patients in the VF. One study reported that prioritizing BLAs over vancomycin resulted in a 52% reduction in 7-day mortality (adjusted OR, 0.48; 95% CI, 0.33-0.69) and a 55% reduction in 48 h mortality (adjusted OR: 0.45; 95% Cl, 0.24-0.83). Similarly, another study found the BLF strategy was associated with a modest reduction in in-hospital mortality (adjusted OR: 0.89; 95% CI: 0.80-0.99). However, no difference was found in the most recent small, single-institution study that included patients with BSIs. <b>Conclusions</b>: The evidence suggests a potential survival benefit for the BLF strategy over VF in patients with suspected or confirmed BSIs. Larger prospective studies are required to confirm the findings.