Cefepime + Vanc > Vanc + Cefepime

Written by Erena Weathers

So you’re in Resus, your very first one. Leibner is yelling, triage is yelling, and your sphincters are *tight*. Suddenly a nurse comes asking about your elderly septic patient, “hey, what do you want to start?” You have heard all-stars like Dr. Spadafore or Dr. Maracheril say the phrase “Vanc, Cefepime” so you repeat those words to the nurse. You think you’re safe, but it turns out YOU MAY BE WRONG AND HERE’S WHY.

Enter Amoah, Joe, et al. “Administration of a β-lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients with Bloodstream Infections.” Clinical Infectious Diseases (2021).

This study supports giving a β-lactam as the first dose antibiotic as opposed to vancomycin, as in cefepime before vanc in the vignette above. β-lactams have broader coverage, can be infused faster (dare I say IV pushed), and cover pathogens that tend to be associated with higher mortality.

As per Journal Feed: “Administration of a β-lactam agent prior to administration of vancomycin was protective against 7-day mortality with an adjusted OR of 0.48 (95%CI: 0.22-0.69) as well as 48 hour mortality with an aOR of 0.45 (95%CI 0.24-0.83). Of those patients with MRSA bacteremia, administration of β-lactam prior to vancomycin did not offer any protective 7-day mortality benefit (aOR 0.93 [95%CI 0.33-2.63]) but neither did administering vancomycin first.”

Why is that? Unfortunately, this is only a retrospective cohort analysis and is unable to detect causation. The authors try to explain the possible causes of this finding.  First, 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. Second, 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. Finally, 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.

So why were you wrong in the vignette? You encouraged vancomycin prior to broad-spectrum β-lactam coverage such as cefepime. So next time, say your broad coverage and then vanc, or encourage your nurses to give vanc last. 


Amoah, Joe, et al. “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. 4 Oct 2021. doi: 10.1093/cid/ciab865. Online ahead of print.

Vivian Lei. “β-lactam or Vancomycin First for Bacteremia?” Journal Feed. 17 Nov 2021. https://journalfeed.org/article-a-day/2021/-lactam-or-vancomycin-first-for-bacteremia

Adam Spaulding. “Trick of the Trade: IV-Push Antibiotics in the ED.” ALiEM. 11 May 2015. https://www.aliem.com/trick-iv-push-antibiotics/