In this episode, I’ll discuss whether the beta-lactam should be given before vancomycin in patients with sepsis that need both antibiotics.
While there is plenty of data to justify efforts to administer antibiotics to patients with sepsis quickly, there is little information to guide whether the order of administration matters when a patient requires both a beta-lactam antibiotic and vancomycin.
A group of authors recently published in Clinical Infectious Diseases a large retrospective analysis looking at the association between beta-lactam vs vancomycin first strategies and in-hospital mortality.
Over 25,000 patient cases were analyzed from a database of 5 US hospitals. All patients had suspected sepsis and were treated with vancomycin and a broad-spectrum beta-lactam within 24 hours of arrival.
About 5 out of every 6 patients received the beta-lactam antibiotic first. Compared to the beta-lactam first group, patients administered vancomycin first were, on average, less severely ill, had nearly 3 times more skin/musculoskeletal infections, and received beta-lactams a median of 3.5h later relative to ED arrival time.
To account for these differences, the authors applied inverse probability weighting (IPW) to adjust for potential confounders. After adjustment the beta-lactam first group had a significantly lower mortality with an adjusted odds ratio of 0.89.
The authors concluded:
Among patients with suspected sepsis prescribed vancomycin and β-lactam therapy, β-lactam administration before vancomycin was associated with a modest reduction in hospital mortality. These findings support prioritizing β-lactam therapy in most patients with sepsis but merit affirmation in randomized trials given the risk of residual confounding in observational analyses.
I believe it is highly unlikely that a randomized trial examining this issue will ever be performed. This would involve deliberately delaying gram-negative coverage for patients with sepsis, and the retrospective data now available may be enough to give an institutional review board a reason to prevent such a study from being conducted.
To get access to my free download area with 20 different resources to help hospital pharmacists go to pharmacyjoe.com/free.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Leave a Reply