Background: The combination of vancomycin (VAN) and anti-pseudomonal beta-lactams has been implicated in increasing incidence of acute kidney injury. It is unknown if this is a recent phenomenon or has been consistently occurring. The objective of this study was to examine the incidence of acute kidney injury over time in patients receiving VAN with piperacillin-tazobactam (PTZ) or cefepime (CFP).
Methods: This is a retrospective cohort study including adult patients admitted to the University of Kentucky HealthCare Enterprise from 1/1/2008 through 9/30/2015 who received at least two days of combination therapy with VAN and PTZ or CFP. Data was collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust. AKI was assessed with the RIFLE criteria.
Results: There were 14,779 patients who met inclusion criteria, with 11,365 (77%) of patients receiving PTZ+VAN and 3,414 (23%) receiving CFP+VAN. The groups were similar in age (53.5±16.6 v 52±16.7 years) and weight (83±24.6 v 83.2±25.1 kg). Patients receiving PTZ+VAN had worse baseline renal function (90.5 [65.4-120.5] v 94.7 [68.8-125.4] mL/min, p <0.00001), and more frequent exposure to additional nephrotoxins, such as aminogylcosides, ACE-inhibitors, and loop diuretics. CFP+VAN patients were more likely to be admitted to the ICU (20.9 vs 16.0%, p<0.00001). Figure 1 shows the trends in AKI incidence and regimen utilization. Overall, AKI incidence in these patients has decreased over time with Q1 2008 having the highest incidence (36%) and Q3 2015 having the lowest (13%; r2 = -0.89, p <0.00001). PTZ+VAN and CFP+VAN utilization was steady until a Q4 2014, in which the national PTZ shortage impacted regimen selection. The incidence of AKI in PTZ+VAN group ranged from 22% to 37% and decreased from the start of the study (r2= -0.85, p <0.0001). Conversely, the rate of AKI in the CFP+VAN averaged 14% and ranged from 0 to 31%, with no trend in either direction (r2= -0.07, p=0.7).
Conclusion: Overall AKI incidence and PTZ+VAN associated AKI are decreasing, while CFP+VAN AKI incidence remains stable over the past 31 quarters. The PTZ shortage beginning in Q4 2014 was associated with a large increase in CFP+VAN utilization but the overall AKI rate continued to decrease.
W. C. Rutter,
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