Abstract
BackgroundContinuous infusion of vancomycin is increasingly preferred as an alternative to intermittent administration in critically ill patients. Intermittent vancomycin treatment is associated with an increased occurrence of nephrotoxicity. This study was designed to determine the incidence and risk factors of acute kidney injury (AKI) during continuous infusion of vancomycin.MethodsThis was a retrospective, observational, two-center, cohort study in patients with microbiologically documented Gram-positive pneumonia and/or bacteremia and normal baseline renal function. Vancomycin dose was adjusted daily aiming at plateau concentrations of 15-25 μg/mL. AKI was defined as an increase in serum creatinine of 0.3 mg/dL or a 1.5 to 2 times increase from baseline on at least 2 consecutive days after the initiation of vancomycin. Primary data analysis compared patients with AKI with patients who did not develop AKI. A binary logistic regression analysis using the forward stepwise method was used to assess the risk factors associated with AKI.ResultsA total of 129 patients were studied of whom 38 (29.5%) developed AKI. Patients with AKI had higher body weight (77.3 ± 15 vs. 70.5 ± 15.2 kg; p = 0.02), more diabetes (79% vs. 54%; p = 0.01), and a higher vasopressor need (87% vs. 59%; p = 0.002). Serum vancomycin levels, body weight, and SAPS 3 score were identified as variables contributing to AKI. The incidence of AKI increased substantially when treatment duration was prolonged (14.9 ± 9.8 vs. 9.2 ± 4.9 days; p = 0.05) and plasma levels exceeded 30 μg/mL.ConclusionsAKI is frequently observed during continuous vancomycin infusion, particularly when conditions that cause acute (shock) or chronic (diabetes) renal dysfunction are present and vancomycin levels above target range are achieved. Although this study challenges the concept that continuous vancomycin infusion might alleviate the risk of nephrotoxicity in critically ill patients, a direct relationship between vancomycin and nephrotoxicity remains to be proven.
Highlights
Continuous infusion of vancomycin is increasingly preferred as an alternative to intermittent administration in critically ill patients
A laboratory computed database was searched to identify all patients with community, hospital, or healthcareacquired pneumonia and bacteremia that had been treated with continuous vancomycin infusion
Baseline creatinine values were comparable between patients with and without acute kidney injury (AKI) (0.9 ± 0.19 mg/dL vs. 0.8 ± 0.35 mg/dL; p = 0.12)
Summary
Continuous infusion of vancomycin is increasingly preferred as an alternative to intermittent administration in critically ill patients. Several reasons might explain why conventional twicedaily dosing of vancomycin often fails to obtain microbiological and clinical cure in patients with Staphylococcus aureus (SA) pneumonia and bloodstream infections: poor penetration in infected and/or ventilated lung tissue, a subtle but significant increase in minimal inhibitory concentration (MIC) over time, referred to as the MIC “creep,” and the emergence of heteroresistant strains [1,2]. These observations have prompted experts to decrease the breakpoint of vancomycin susceptibility from 4 to 2 μg/mL and to recommend targeting serum vancomycin trough levels of 15-20 μg/mL for the treatment of methicillin-resistant SA (MRSA) pneumonia [3]. Intensive care unit (ICU) patients are exposed to a wide array of potential nephrotoxic agents, which increases the risk for vancomycin-associated nephrotoxicity
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