Russell J. Benefield, PharmD

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A new study shows continuous infusions of vancomycin is not necessarily more beneficial than intermittent infusions for patients in an outpatient parenteral antimicrobial therapy program.¹

A team, led by Russell J. Benefield, University of Utah Health, Department of Pharmacy, compared safety and other outcomes for patients treated with continuous compared to intermittent infusions of vancomycin.

The Treatment

While there is some data showing continuous infusions of vancomycin is linked to reduced nephrotoxicity, there is limited research into continuous infusion vancomycin in outpatient parenteral antimicrobial therapy programs.

In the retrospective, single-center study, the investigators examined adult patients treated with vancomycin outpatient parenteral antimicrobial therapy programs as continuous or intermittent infusion for at least 7 days.

The investigators sought primary outcomes of the time to nephrotoxicity with continuous compared to intermittent infusion vancomycin while on outpatient parenteral antimicrobial therapy. They also looked at additional outcomes of time to any vancomycin-associated adverse event, time to 60-day death or readmission, and time to 60-day emergency department encounter.

The investigators used proportional hazards modeling to identify variables independently associated with outcomes and to assess the strength of association of continuous infusion with each outcomes.

The Study

Overall, the study included 492 patients, 118 treated with continuous infusions and 374 treated with intermittent vancomycin infusions.

The results show continuous infusions were not linked to lower rates of nephrotoxicity compared to intermittent infusions (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.35-1.50).

There were also no advantages found of continuous infusions compared to intermittent infusions in the rates of any adverse event (aHR, 0.93; 95% CI, 0.56-1.53).

The same was found for the other outcomes, including 60-day death or readmission (aHR, 1.04; 95% CI, 0.68-1.61) or 60-day emergency department encounter (aHR, 1.17; 95% CI, 0.68-1.99).

The area under the concentration-time curve (AUC) for vancomycin at discharge was the only modifiable factor found that was independently associated with patient safety outcomes.

“There was no appreciable benefit of continuous infusion vancomycin on outpatient safety outcomes. AUC-centered dosing approaches warrant further investigation as strategies to improve vancomycin safety in OPAT programs,” the authors wrote.

Vancomycin

A recent research letter highlighted that for patients receiving vancomycin, being younger than 50 and having high vancomycin trough levels may be risk factors for drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.²

As one of the main therapies designed for antibiotic-resistant gram-positive infections, vancomycin was seen as important to assess given the danger associated with the therapy and given the higher fatality rate of vancomycin DRESS syndrome.

The investigators conducted a case-control study through the use of Mass General Brigham (MGB) electronic health record data, assessed from 2013 through 2021. They confirmed potential cases of DRESS syndrome thanks to research fellows and through the guidance of board-certified specialists.

Within the investigators’ adjusted models, patients who were less than 50-years-old were associated with a higher vancomycin DRESS syndrome risk (adjusted OR [aOR], 3.21; 95% CI, 1.33-7.78). Although hypertension was found to be inversely associated with DRESS syndrome (aOR, 0.45; 95% CI, 0.25-0.82), they found no comorbidities associated with increased risk of DRESS.

The investigators also noted that a vancomycin trough of over 25 μg/mL and 30 μg/mL did have an association with greater risk of DRESS (aOR, 2.32 [95% CI, 1.18-5.11] and 8.69 [95% CI, 3.39-22.27], respectively).