Vancomycin Use in ICU Incurs Greater AKI Risk Than Alternative Antibiotics

Findings from a recent target trial emulation study suggest vancomycin causes a higher risk of acute kidney injury than alternative antibiotics like clindamycin and linezolid, necessitating compliance with established prevention strategies.1

The research investigated the effect of initiating vancomycin versus initiating one of several minimally nephrotoxic alternative antibiotics on the 14-day risk of AKI in adult intensive care unit (ICU) admissions and found a heightened risk with vancomycin. Accordingly, investigators recommend strategies like dosing vancomycin according to renal function, therapeutic drug monitoring, and the consideration of a non-nephrotoxic alternative antibiotic where applicable.1

“AKI is a frequent syndrome in ICU patients and is often caused by drugs,” Izak Yasrebi-de Kom, PhD, of Amsterdam University Medical Center, and colleagues wrote.1 “Optimizing pharmacotherapy may reduce the risk of drug-induced AKI and associated negative outcomes”

A tricyclic glycopeptide antibiotic used to treat severe gram-positive bacterial infections, vancomycin has been linked to several adverse side effects, including nephrotoxicity, hypotension, and hypersensitivity reactions. However, evidence regarding its potential to cause AKI in adult intensive care patients is conflicting.1,2

To estimate the effect of initiating vancomycin versus other minimally nephrotoxic alternative antibiotics on AKI risk, investigators conducted a target trial emulation study with an active comparator, new user design. They reused routinely collected electronic health record (EHR) data of admissions to 15 Dutch ICUs between January 2010 and December 2019 and linked them to data from the Dutch National Intensive Care Evaluation quality registry.1

Investigators’ hypothetical trial enrolled adult, non-dialysis dependent AKI-free ICU admissions with a suspected bacterial infection that was perceived to be treatable with vancomycin or 1 of the 6 following alternative antibiotics: clindamycin, linezolid, teicoplanin, meropenem, cefazolin, or daptomycin. Additionally, ICU admissions were only eligible for enrollment after 24 hours and before 7 days post-ICU admission. A baseline serum creatinine (SCr) measurement in the first 24 hours of the ICU admission was also required for inclusion.1

In the hypothetical trial, follow-up started at the time of treatment assignment and ended at AKI diagnosis, loss to follow-up, initiation of the other treatment strategy, initiation of kidney replacement therapy (KRT) without preceding AKI, death, or 14 days after treatment assignment, whichever occurred first. In the emulation, follow-up started at initiation of treatment and ended at AKI diagnosis, discharge from the ICU, initiation of the other treatment strategy, initiation of KRT without preceding AKI, death, or 14 days after treatment initiation, whichever occurred first.1

The outcome of interest was AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria.1

Among a cohort of 176,489 ICU admissions, 30,510 initiated one of the treatment strategies and 1809 met all eligibility criteria. Of these, 887 initiated vancomycin and 922 initiated an alternative antibiotic.1

After adjustment, initiation of vancomycin was associated with a heightened risk of AKI at 14 days of follow-up compared to initiation of an alternative antibiotic (0.28; 95% CI, 0.21 to 0.34 vs 0.17; 95% CI, 0.14 to 0.20; risk difference, 0.11; 95% CI, 0.04 to 0.19), but not at 2 days of follow-up (0.10; 95% CI, 0.06 to 0.12 vs 0.10; 95% CI, 0.08 to 0.11; risk difference, 0.00; 95% CI, −0.03 to 0.03).1

In exploratory dose-response analyses, after excluding the ICU admissions that were lost to follow-up before the 24-hour landmark, 1328 admissions remained, of whom 652 initiated an alternative antibiotic, 322 initiated vancomycin with the lower starting dose, and 354 initiated vancomycin with the higher starting dose. After adjustment, both the higher and the lower vancomycin doses were associated with an increased risk of AKI at 14 days of follow-up compared to the initiation of an alternative antibiotic. However, investigators noted the higher vancomycin dose had a bigger risk difference point estimate (0.17; 95% CI, 0.05 to 0.25 vs 0.10; 95% CI, 0.01 to 0.19).1

“Our findings indicate that vancomycin causes a higher risk of AKI compared to the investigated alternative antibiotics,” investigators concluded.1 “We recommend clinicians to be compliant with clinical vancomycin-induced AKI prevention strategies. Future research on dose–response relationships is warranted.”

References

1. Yasrebi-de Kom IAR, Jager KJ, Stel VS, et al. Vancomycin-Induced Acute Kidney Injury in Intensive Care Patients: A Target Trial Emulation Study Using Multicenter Routinely Collected Data. PDS. https://doi.org/10.1002/pds.70205

2. Patel S, Preuss CV, Bernice F. Vancomycin. StatPearls. October 29, 2024. Accessed August 29, 2025. https://www.ncbi.nlm.nih.gov/books/NBK459263/