In this episode, I’ll discuss which antibiotic should be given first in sepsis – the beta-lactam or the vancomycin?
Quickly administering appropriate empiric antibiotic therapy is essential in the treatment of severe infections. If multiple antibiotics are required for empiric therapy to treat a severe infection (such as for empiric coverage of resistant gram-negative and gram-positive organisms), simultaneous administration can be appropriate. However, IV access, antibiotic compatibility, and other resources may require that antibiotic administration be sequential.
To determine whether the order of administration for beta-lactams and vancomycin had an impact on mortality when treating suspected bacteremia, researchers conducted a multicenter, observational study and recently published it in Clinical Infectious Diseases.
Data from over 3000 patients were analyzed. Beta-lactams were administered before vancomycin in a 4:1 ratio in the patient cohort.
The authors found that administration of a beta-lactam antibiotic prior to vancomycin protected against 7-day mortality with an adjusted odds ratio 0.48. Protection against 48 hour mortality also resulted in similar results with an adjusted odds ratio of 0.45.
As would be expected however, not all bacteremias were adequately covered by beta-lactams after culture and sensitivity data became available with almost 1 in 7 patients having a bacteremia caused by MRSA. Interestingly, when vancomycin was given before the beta-lactam to these patients with MRSA bacteremia, there was no statistically significant improvement in 48 hour or 7 day mortality rates.
The authors concluded:
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.
The results of this study appear to have been confirmed with an even larger 25,000+ patient retrospective analysis also published in Clinical Infectious Diseases.
Beta-lactams were administered before vancomycin in a 5:1 ratio in this patient cohort. All patients had suspected sepsis.
On inverse probability weighting analysis, the beta-lactam-first strategy was associated with lower mortality with an adjusted odds ratio of 0.89. While less impressive than the first study, this was statistically significant.
These 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 in-hospital mortality. These findings support prioritizing β-lactam therapy in most patients with sepsis but merit confirmation in randomized trials given the risk of residual confounding in observational analyses.
The article in this episode is a selection from my Hospital Pharmacy Academy’s weekly literature digest. Have you ever felt like your physician colleagues are one step ahead of you with new literature developments? Every week, Academy members are provided a summary curated and explained by me of the top hospital pharmacy-related articles published that week from over 20 major journals and sources to save you time and keep you up to date with the literature. To get immediate access, go to pharmacyjoe.com/academy.
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.
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