Influence of Beta-Lactam Infusion Strategy on Acute Kidney Injury

• Retrospective, matched cohort comparison of adults admitted from July 2006 to September 2015 who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for > 48 hours • Exclusion criteria: pre-existing renal dysfunction (CKD Stage 3 or higher or on renal replacement therapy), pregnancy, breastfeeding • Data extracted from University of Kentucky Center for Clinical and Translation Science Enterprise Data Trust • Matched on beta-lactam received, age, gender, vancomycin exposure, Charlson score, baseline CrCl, hypotension, ICU admission • Concomitant nephrotoxins defined as receipt of at least 1 dose of the drug during or within 24 hour of beta-lactam treatment • AKI defined by RIFLE criteria3 where risk is ≥25% decrease in GFR, injury is ≥ 50% decrease in GFR, and failure is >75% decrease in GFR. Background: Prolonged beta-lactam infusions have been promoted as a strategy to optimize time-dependent bactericidal activity. Limited literature is available assessing nephrotoxicity in prolonged infusions. The objective of this study was to compare the incidence of acute kidney injury (AKI) associated with a prolonged beta-lactam infusion (PI) or a bolus infusion. Methods: Adult patients admitted from July 2006 to September 2015 who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 hours were evaluated. Patients were excluded for pre-existing renal dysfunction, or pregnancy. Clinical data were extracted from our institution’s Center for Clinical and Translation Science Enterprise Data Trust. AKI was evaluated using the RIFLE criteria. Patients in the bolus group were matched to patients in the PI group based on the following: beta-lactam agent, age, gender, Charlson Comorbidity Index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in intensive care unit. Results: Of 19,034 patients evaluated, a total of 3843 were included in our matched analysis with 2747 receiving bolus infusions (53% TZP, 35% FEP, 12% MEM) and 1096 receiving PI (45% TZP, 30% FEP, 25% MEM). The overall age of the population was 44.9+17.8 years with the majority being males (60.4%) and Caucasian (91.3%). The PI cohort had a longer length of stay [11 (6-17) vs 8 (5-16) days, p <0.001] and more cystic fibrosis (CF) patients [39.8% vs 3.4%, p <0.001] than the bolus group. The incidence of AKI was higher in the PI group compared to bolus infusions (21.4% vs 17.6%, p = 0.006), with the difference being seen in the risk stratification (15% vs 11%). After multivariate regression, PI was not associated with increased odds of AKI [OR of 1.07 (95% CI 0.85-1.33)]. Independent predictors of AKI included: concomitant nephrotoxins, age ≥65 [OR 1.23 (95% CI 1.03-1.94)], hypotension [OR 1.23 (95% CI 1.01-1.49)], diabetes [OR 1.34 (95% CI 1.09-1.66)], CF [OR 1.78 (95% CI 1.29-2.45)], and TZP therapy [OR 1.97 (95% CI 1.61-2.42)]. Conclusion: Although AKI was more common in patients receiving prolonged beta-lactam infusions than those receiving bolus infusions, prolonged infusion was not found to be an independent risk factor for AKI.