Examining Beta-Lactams With Vancomycin for Bloodstream Infections for MRSA

When treating bloodstream infections (BSIs) due to methicillin-resistant Staphylococcus aureus (MRSA), the first-line of care is to prescribe monotherapy vancomycin (VAN). In the literature, however, there has been in vitro and clinical evidence to suggest a combination of certain beta-lactam antibiotics and vancomycin is efficacious against MRSA.

At the Detroit Medical Center, a MRSA BSI treatment pathway was implemented, which incorporates early use of combination therapy with VAN and cefazolin (CFZ). Subsequently, a group of investigators at the medical center wanted to study patients receiving vancomycin monotherapy vs combination therapy with VAN + CFZ for treatment of MRSA BSIs.

“There have been no studies that have exclusively looked at vancomycin and cefazolin together," said study investigator Kaylee Caniff, PharmD, BCIDP, postdoctoral research fellow, Infectious Diseases Outcomes, Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University. "[We] found that there was a reduced mortality rate when combining cefazolin within the first five days of bacteremia compared to vancomycin monotherapy.”

“VAN + CFZ was associated a lower 30-day mortality rate (3.4% vs. 9.8%, p = 0.022) and shorter duration of bacteremia (49.0 [35.0-74.0] hours vs. 62.0 [42.0-95.8] hours, p = 0.005),” the investigators reported. “After adjusting for confounders, VAN + CFZ receipt was independently associated with reduced 30-day mortality (aOR 0.31, 95% CI 0.11-0.93).”

Study Criteria

This was a retrospective, observational study of patients hospitalized with MRSA BSI at the Detroit Medical Center from 2006-2021. Patients included in the study were initiated on vancomycin within 72 hours of the index culture. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality.

Exclusion criteria included those patients that received < 5 days of vancomycin, transferred to an outside hospital, received an alternative anti-MRSA antibiotic, received > 5 days of non-CFZ beta-lactam, or initiated on CFZ > 120 hours after index culture.

The investigators noted that except for the combination therapy group more likely to receive an infectious diseases clinician consult, there were no significant differences between the 2 cohorts for infectious source, demographics, comorbidities, MRSA risk factors, and illness severity.

“Mortality is where we found the benefit. We did not find a difference in persistent bacteremia,” said Caniff. “It trended towards that direction, but it was not significant. I think this is likely because my study had less complicated cases due to the exclusionary criteria."

A total of 359 patients were included with 145 patients receiving VAN + CFZ in the one cohort, and and 214 receiving monotherapy VAN in the other.

“In patients with MRSA BSI, the addition of CFZ to VAN within 120 hours of index culture was associated with improved outcomes. To our knowledge, this is the first study specifically examining VAN + CFZ in this population,” the investigators reported.

Contagion spoke to Caniff recently at IDWeek who provided more insights on the study and the takeaways from it.

Reference

Caniff K, Coyne A, Rybak M. Unexpected Allies: Vancomycin and Cefazolin Combination Therapy in Methicillin-Resistant Staphylococcus aureus Bacteremia. Presented at: IDWeek 2023. October 11-14, 2023; Boston, MA. Abstract 1033.