Bloodstream infections (BSIs) are associated with significant morbidity and mortality. Prompt initiation of empiric antibiotics improves patient survival, but not much is known about the sequence of antibiotic administration.
A 2022 study in Clinical Infectious Diseases looked at whether administration of a broad-spectrum β-lactam (e.g., cefepime, piperacillin-tazobactam, etc.) before the infusion of vancomycin, as the first dose of antibiotic therapy, is protective against mortality in the first 7 days for hospitalized patients with BSIs. Of 3376 eligible patients across 5 hospitals, 2685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic.
- Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (aOR 0.48 [95% CI 0.33-0.69]). Similar results were observed when evaluating 48-hour mortality (aOR 0.45 [95% CI 0.24-0.83]).
- Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with MRSA BSI (aOR 0.93 [95% CI 0.33-2.63]), supporting the overall study findings of prioritizing β-lactam therapy when there is a heightened suspicion for BSI.
The authors propose 3 mechanisms to explain their findings:
- The prevalence of bacterial pathogens causing BSIs susceptible to broad spectrum β-lactams is higher than the prevalence of pathogens not susceptible to broad-spectrum β-lactams.
- Significant endotoxin release with the first dose of antibiotic therapy is a known phenomenon that may occur during the treatment of gram-negative pathogens. The likelihood of a severe cytokine storm from endotoxin release is likely to be more dramatic and contribute to poor outcomes as the bacterial burden increases, as theoretically occurs in the absence of prompt antibiotic therapy.
- Patients with severe immunocompromise, particularly those with profound neutropenia, are at higher risk of mortality when infected with bacterial pathogens compared to patients with competent immune systems, and the former are more likely to be infected with gram-negative bacteremia rather than MRSA bacteremia.
In sum, for patients likely to be experiencing BSI, prioritizing administration of a β-lactam over vancomycin appears to reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.
tl;dr In patients with suspected bloodstream infection, administering the β-lactam before vancomycin reduced 7-day mortality by 52%! And in patients with MRSA, administering vancomycin first was not associated with improved survival.