RecruitingPhase 4NCT06954129

A Pragmatic Clinical Trial Comparing the Risk of Acute Kidney Injury During Treatment With Vancomycin and Piperacillin-Tazobactam vs. Vancomycin and Cefepime in Hospitalized Patients

Markers of Nephrotoxicity During Treatment With Antibiotic Combinations: A Pragmatic Clinical Trial

Sponsor

University of Pennsylvania

Enrollment

750 participants

Start Date

Jan 28, 2026

Study Type

INTERVENTIONAL

Conditions

Acute Kidney Injury

Summary

Hospitalized patients with suspected or confirmed infection are commonly treated with vancomycin (VN) in combination with either piperacillin-tazobactam (PT) or cefepime (CP). Although these regimens have similar effectiveness, recent observational evidence suggests they may differ in terms of the risk for acute kidney injury (AKI). Interpretation of existing evidence is complicated by the limitations of creatinine, the standard biomarker used to monitor kidney function, which has poor sensitivity and specificity for drug induced AKI. To address this important knowledge gap, the investigators propose to conduct a pragmatic, open-label, non-inferiority trial that will examine the comparative risk of AKI between these standard-of-care antibiotic combinations using sensitive and specific markers of drug-induced AKI. We hypothesize that the regimen of VN in combination with PT (VN+PT) is noninferior to the regimen of VN in combination with CP (VN+CP) in terms of AKI risk.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

Age of at least 18 years
Suspected or confirmed infection based on clinical criteria, for which vancomycin with piperacillin-tazobactam or vancomycin with cefepime was prescribed by the treating clinician, as evidenced by orders being placed in the electronic health record
The treating clinician considers both vancomycin with piperacillin- tazobactam or vancomycin with cefepime as acceptable treatment
The treating clinician anticipates at least 48 hours of antibiotic treatment

Exclusion Criteria11

Dialysis dependence or documented end stage kidney disease
AKI at baseline
Expected survival <24 hours and/or presence of do not resuscitate orders
History of antibiotic-resistant organisms (microbiological culture results showing bacterial isolates with resistant or intermediate susceptibility to any study drug within the prior 90 days)
Documented allergy to vancomycin, cephalosporins, or penicillin
Suspected central nervous system infection
Inability to provide informed consent or lack of proxy for consent
Prisoners/incarcerated individuals
Known pregnancy or breastfeeding
Previous enrollment in this study
Receipt of vancomycin, piperacillin-tazobactam, or cefepime for >24 hours within the preceding 7 days. At the time of screening, one-time doses of vancomycin, with or without piperacillin-tazobactam, or cefepime, will be allowed prior to randomization to avoid treatment delays; such patients must be enrolled within twelve hours of antibiotic administration.

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Interventions

DRUGVancomycin

Vancomycin is a glycopeptide antibiotic used to treat infections caused by Gram-positive bacteria, including those due to methicillin-resistant Staphylococcus aureus. Dosing of vancomycin will follow standard of care procedures, including the use of individualized dosing regimens developed in consultation with clinical pharmacists, based on participant body weight and renal function, and dosage titration guided by therapeutic drug monitoring. Vancomycin is administered via intermittent intravenous infusions of 60-90 minutes.

DRUGPiperacillin-tazobactam

Piperacillin-tazobactam is an anti-pseudomonal penicillin with a dose range of 2.25 g or 4.5 g and frequency of every 6 or 8 hours based on a participant's body weight, renal function, and clinician discretion. Piperacillin-tazobactam is administered via extended-duration (4 hours) intravenous infusions

DRUGCefepime

Cefepime is an anti-pseudomonal cephalosporin with a dose range of 500 mg, 1,000 mg, or 2,000 mg, and frequency every 8, 12, or 24 hours based on a participant's body weight, renal function, and clinician discretion. Cefepime is administered via extended-duration (4 hours) intravenous infusions