Administration of a β-Lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients With Bloodstream Infections

Clin Infect Dis. 2022 Aug 24;75(1):98-104. doi: 10.1093/cid/ciab865.


Background: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSIs). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (ie, β-lactam or vancomycin, if both are deemed necessary and cannot be administered simultaneously) impacts early mortality for patients with BSI.

Methods: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on demographics, Pitt bacteremia score, intensive care unit status, highest lactate, highest white blood cell count, Charlson comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose.

Results: Of 3376 eligible patients, 2685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (adjusted odds ratio [aOR], 0.48 [95% confidence interval {CI}, .33-.69]). Similar results were observed when evaluating 48-hour mortality (aOR, 0.45 [95% CI, .24-.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR, 0.93 [95% CI, .33-2.63]).

Conclusions: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

Keywords: antibiotics; bacteremia; mortality; sepsis; β-lactam.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents
  • Bacteremia* / drug therapy
  • Humans
  • Lactams / therapeutic use
  • Methicillin-Resistant Staphylococcus aureus*
  • Retrospective Studies
  • Staphylococcal Infections* / drug therapy
  • Treatment Outcome
  • Vancomycin / therapeutic use
  • beta-Lactams / therapeutic use


  • Anti-Bacterial Agents
  • Lactams
  • beta-Lactams
  • Vancomycin