December 15, 2021
By Christopher J. Graber, MD, MPH, FIDSA
Empiric antimicrobial therapy for patients with suspected bloodstream infection frequently consists of a β-lactam plus vancomycin. However, little thought is typically given to which agent should be administered first. Arguments in favor of administering the β-lactam first include a greater likelihood of treating etiologic agents of sepsis (especially gram-negative bacteria) and shorter time of infusion.
Authors of a recent study in Clinical Infectious Diseases retrospectively examined a cohort of 3,376 patients from five hospitals in an academic health care system who were treated with a β-lactam-vancomycin combination within 6 hours of blood culture collection and found to be bacteremic with a gram-positive or gram-negative organism from July 2016 to June 2020. Inverse probability of treatment weighting based on propensity scores that included demographics, comorbidities and illness characteristics (including time from emergency department arrival to first dose of antibiotics) were used to adjust for potential selection bias in the order in which antibiotics were given. In the cohort, 2,685 (79.5%) patients received the β-lactam first, with piperacillin-tazobactam (47.9%) and cefepime (42%) being the most common agents. The most common causes of bacteremia were Staphylococcus aureus (22.5%, 42.3% of which was methicillin-resistant), Escherichia coli (20.8%) and Klebsiella pneumoniae (13.9%).
Administration of a β-lactam before vancomycin was associated with lower 7-day mortality in weighted regression analysis with an adjusted odds ratio (aOR) of 0.48 (95% confidence interval [CI], 0.33-0.69); results for 48-hour mortality were similar (aOR, 0.45 [95% CI, 0.24-0.83]). Importantly, in patients with methicillin-resistant S. aureus bacteremia, aOR for 7-day mortality among patients who received the β-lactam first was 0.93 (95% CI, 0.33-2.63).
This work provides fairly compelling evidence for a likely simple intervention at most institutions to prioritize β-lactam administration prior to vancomycin for patients with suspected bacteremia and should spur study of antibiotic sequencing for other indications as well.