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Short courses of PTZ/VAN do not increase risk for acute kidney injury

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August 30, 2018

Short courses of piperacillin/tazobactam and vancomycin are not associated with a greater risk for moderate to severe acute kidney injury when compared with similar antibiotic combinations, according to results from a study in critically ill patients.

Writing in Clinical Infectious Diseases, Diana J. Schreier, PharmD, pharmacy informatics resident at the Mayo Clinic in Rochester, Minnesota, and colleagues noted that nephrotoxins contribute to up to 40% of acute kidney injuries (AKI), and that the extended durations of piperacillin/tazobactam and vancomycin (PTZ/VAN) have been identified as nephrotoxic.

“Empiric selection of antibiotics in critically ill patients is a delicate balance between selecting the appropriate agents to treat the infection, limiting host toxicity, and optimizing antimicrobial stewardship,” they wrote. “Current guidelines clearly prioritize broad-spectrum therapies for septic patients, which results in widespread use of intravenous antipseudomonal beta-lactams and drugs to treat resistant gram-positive infections.”

To determine risk for AKI in patients with brief exposures to PTZ/VAN, Schreier and colleagues conducted a retrospective cohort study among ICU patients comparing a short course of the combination with other antipseudomonal beta-lactam/vancomycin combinations.

Any adults 18 or older who were hospitalized in an ICU at the Mayo Clinic between Jan. 1, 2006, and Dec. 31, 2016, were eligible for the study. Eligibility required between 24 and 72 hours of an antipseudomonal beta-lactam and vancomycin — such as PTZ/VAN, cefepime (CEF/VAN) or meropenem (MER/VAN). Antibiotic groups were compared to determine the risk for developing stage 2 or 3 AKI, persistent kidney dysfunction, dialysis dependence or death at 60 days.

Of the 3,299 eligible patients, Schreier and colleagues observed a 9% overall incidence of stage 2 or 3 acute kidney injury. When compared with CEF/VAN (adjusted OR = 1.11; 95% CI, 0.85-1.45) and MER/VAN (aOR = 1.04; 95% CI, 0.71-1.42), PTZ/VAN did not pose a greater risk for stage 2 or 3 AKI, according to the study. At the 60-day follow-up, no significant differences were observed between the antibiotic groups for persistent kidney dysfunction (P =.081), new dialysis dependence (P =.15) or death (P =.091). In patients who received PTZ/VAN and developed stage 2 or 3 AKI, 60% recovered to less than 2-fold baseline by discharge. Comparatively, 38% of patients in the CEF/VAN group and 80% of patients in the MER/VAN group recovered similarly to those in the PTZ/VAN group. Duration of stage 2 or 3 AKI was 2.1, 3.5 and 2.5 days for PTZ/VAN (interquartile range [IQR] 0.6, 3.7), CEF/VAN (IQR 1.1, 5.7) and MER/VAN (IQR 0.8, 3.8), respectively.

Schreier and colleagues said further research is needed to understand the underlying mechanism of previous associations between PTZ/VAN and AKI.

“Recently, nephrotoxicity has been raised as a possibility with PTZ/VAN therapy, which has led to concern over using this combination in the empiric setting,” Schreier and colleagues wrote. “In contrast to previous literature, in this large cohort study of critically ill patients, we found that brief exposure to the combination of PTZ/VAN conferred no greater risk of moderate to severe AKI than similar such exposures to CEF/VAN or MER/VAN.” – by Marley Ghizzone

Disclosures: Schreier reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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