Category: Pharmacology & Therapeutics
Keywords: sepsis, beta-lactam, vancomycin, antibiotic (PubMed Search)
Posted: 6/13/2025 by Alicia Pycraft
Click here to contact Alicia Pycraft
Background:
Early antibiotic administration is consistently linked to improved mortality outcomes in patients with sepsis. As a result, time-to-antibiotic delivery is a critical metric in hospital sepsis quality improvement initiatives. Empiric treatment often consists of a broad-spectrum beta-lactam to cover both gram-positive and gram-negative organisms, alongside vancomycin to ensure coverage of methicillin-resistant Staphylococcus aureus (MRSA). When multiple agents are indicated, they may be given simultaneously; however, factors such as limited intravenous (IV) access or drug incompatibilities can necessitate sequential administration. Administration of vancomycin first may delay the administration of a beta-lactam agent by at least 60-120 minutes due to its prolonged infusion time. This raises an important clinical question: Does the order in which antibiotics are administered influence outcomes in sepsis?
A 2022 retrospective study by Amoah et al. found that, among patients with confirmed bloodstream infections, a beta-lactam-first regimen was associated with a 52% reduction in the odds of short-term mortality compared to a vancomycin-first regimen. However, the generalizability of these findings to the broader population of patients with suspected sepsis, of whom only 15-20% ultimately have positive blood cultures, remains uncertain.
What's new?
A recent retrospective, multi-center, cohort study by Kondo et al. evaluated the impact of a beta-lactam-first antibiotic strategy compared to a vancomycin-first strategy on in-hospital mortality in patients with suspected sepsis. Of the 25,391 patients with sepsis who were screened, 21,449 (84.4%) received a beta-lactam first and 3,942 (15.6%) received vancomycin first. Patients who received vancomycin first had lower comorbidity burden, lower illness severity, more skin/musculoskeletal infections, and received beta lactams a median of 3.5 hours later relative to ED arrival compared to those who received a beta-lactam first. Although the overall rate of documented bloodstream infections was similar between groups, MRSA-positive cultures were more common in the vancomycin-first group, both in clinical cultures (4.5% vs. 3.2%) and in blood cultures (1.8 vs. 1.2%).
Beta-lactam administration prior to vancomycin was associated with an 11% reduction in the odds of in-hospital mortality (aOR: 0.89; 95% CI: 0.8-0.99; p=0.046). When the time-to-first antibiotic covariate was replaced with time-to-first beta-lactam, this association was no longer significant (aOR 0.93, 95% CI: 0.82-1.05, p=0.25), suggesting a possible link between time-to-first beta-lactam antibiotic and mortality. There was a trend toward lower in-hospital morality for the beta-lactam first regimen in several subgroups examined, including patients with positive blood cultures or positive MRSA cultures, and patients who received anti-pseudomonal beta-lactams; however, none reached statistical significance.
Bottom line:
Given the observed mortality benefit and absence of harm associated with a beta-lactam-first approach, even among patients with positive MRSA cultures, the findings of this study support the prioritization of beta-lactam therapy in patients with sepsis.
