Disclosures: Sanders reports receiving grants or contracts with the Society of Infectious Diseases Pharmacists Young Investigator Award and Merck Investigator Initiated Research Grant that here paid to his institution for research outside the submitted work. Cutrell and Tamma report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
October 16, 2021
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Beta-lactams before vancomycin reduces mortality from bloodstream infections

Disclosures: Sanders reports receiving grants or contracts with the Society of Infectious Diseases Pharmacists Young Investigator Award and Merck Investigator Initiated Research Grant that here paid to his institution for research outside the submitted work. Cutrell and Tamma report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Administering a beta-lactam antibiotic before vancomycin significantly reduced mortality rates among patients being treated for bloodstream infections, according to a study published in Clinical Infectious Diseases.

Pranita D. Tamma

“I always hypothesized that for patients presenting with clinical signs and symptoms concerning for bacteremia, that if both a beta-lactam agent and vancomycin are being ordered, the beta-lactam is more critical to infuse first,” Pranita D. Tamma, MD, MHS, director of the pediatric antimicrobial stewardship program and associate professor of pediatrics at the Johns Hopkins School of Medicine, told Healio.

“This is in part because, based on numbers, a broad-spectrum beta-lactam is more likely to provide coverage for organisms that commonly cause bloodstream infections compared to vancomycin, and additionally, a broad-spectrum beta-lactam is more likely to be active against organisms with the highest likelihood of early mortality,” Tamma said.

Tamma and colleagues conducted a multicenter, observational study of patients aged 13 years or older with bloodstream infections (BSIs) who received both a beta-lactam and vancomycin “to evaluate the association of the sequence of antibiotic administration” with mortality rates.

In a related editorial, James B. Cutrell, MD, and James M. Sanders, PhD, PharmD, from the University of Texas Southwestern Medical Center, called the study design “elegant.”

“Given the observational study design, they employed inverse probability of treatment weighting (IPTW) based on propensity scores using key demographic, comorbidity, severity of illness, and treatment variables to adjust for selection bias,” Cutrell and Sanders wrote. “They then used weighted regression analysis to estimate the odds ratio of mortality in the IPTW cohort and doubly robust estimation to adjust for additional potential confounding.”

Of 3,376 patients included in the study, 2,685 (79.5%) received a beta-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. According to the study, in the weighted cohort, exposed and unexposed patients were similar on all baseline variables.

The study demonstrated that administration of a beta-lactam agent before vancomycin reduced 7-day mortality by 52% (adjusted OR = 0.48; 95% CI, 0.33-0.69) and 48-hour mortality by 55% (aOR = 0.45; 95%, CI 0.24-0.83).

Additionally, among a subgroup of more than 500 patients with MRSA BSI, administering vancomycin before a beta-lactam was not associated with improved survival (aOR = 0.93; 95% CI, 0.33-2.63).

“Our study suggests that when presented with a critically ill patient who may be experiencing a bloodstream infection, it is prudent to administer the beta-lactam agent first, if both agents are clinically indicated and cannot be administered simultaneously,” Tamma said. “This simple change in practice has the potential to improve the likelihood of survival.”

References:

Amoah J, et al. Clin Infect Dis. 2021;doi:10.1093/cid/ciab865.

Cutrell JB and Sanders JM. Clin Infect Dis. 2021;doi:10.1093/cid/ciab871.