Reduction in Nephrotoxic Antimicrobial Exposure Decreases Associated Acute Kidney Injury in Pediatric Hematopoietic Stem Cell Transplant Patients

Abstract

Exposure to nephrotoxic medications is a common risk factor for acute kidney injury (AKI) in pediatric stem cell transplantation (SCT). We hypothesized that reducing nephrotoxic antimicrobial exposure for SCT patients would be associated with lower nephrotoxin-associated AKI (NTMx-AKI) rates and no increase in infection treatment failures. We conducted a prospective cohort analysis of all inpatient SCT patients at Cincinnati Children's Hospital Medical Center between January 2014 and December 2017. In January 2016, first line fever coverage was changed from piperacillin-tazobactam to cefepime, acknowledging that the change resulted in a loss of enterococcal coverage, and the duration of antimicrobial exposures was limited, specifically including vancomycin. We collected data using prospective NTMx-AKI and antimicrobial utilization monitoring platforms within the electronic health record. AKI days and severity were extracted for patients exposed to 3+ nephrotoxins, 3+ days of IV aminoglycosides, or 3+ days of IV vancomycin. AKI was identified using KDIGO serum creatinine criteria. We assessed rates of nephrotoxin exposure and NTMx-AKI in all SCT inpatients for 2 years pre-and post-intervention. Data were grouped and analyzed by calendar month, normalized to a denominator of 1000 patient-days. Statistical process control methods were used to monitor adherence to the intervention and identify changes in mean rate of nephrotoxin exposure and NTMx-AKI. Infection rates, alternate antimicrobial usage rates, and the fraction of repeat positive cultures were used to identify treatment failures. PTZ usage decreased from 196 to 33 days/1000 patient days, cefepime usage increased from 62 to 290 days/1000 patient days, and vancomycin usage decreased from 62 to 41 days/1000 patient days. High nephrotoxin exposure decreased by 33% (143 to 96 days/1000 patient days), and NTMx-AKI decreased by 74% (24 to 6 days/1000 patient days). Rates of all KDIGO stages of NTMx-AKI decreased 50% after the intervention. Stage 3, the most severe, decreased by >80%. The fraction of repeat positive cultures remained stable between the two eras at .1 (standard deviation 0.21) and .07 (standard deviation 0.17), respectively. There were no increases in infection rates, alternate antimicrobial usage rates, or treatment failures. Reduction of nephrotoxic antimicrobial exposure can decrease the amount and severity of NTMx-AKI in SCT patients without an increase in treatment failures.

Acute Kidney Injury Following Pediatric Liver Transplant

“…7,13,19 Benoit et al investigated a change in protocol from piperacillin/tazobactam to cefepime in their pediatric hematopoietic stem cell transplantations and found a decrease in AKI rates without the feared complication of enterococcal infection in any of their 203 subjects. 28 The potential for changes in drug protocols to decrease AKI risk in pediatric liver transplant patients is an important area for future investigation.…”

Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

“…Surgery is sometimes performed in patients with established AKI; however, common perioperative interventions focus on prevention of PO-AKI (Box 3 ). As nephrotoxic drugs are an important preventable contributor to the risk of PO-AKI, exposure to these drugs should be limited whenever possible and the benefits of the intervention weighed against the risk of developing or worsening AKI 62 . Although the avoidance of potential nephrotoxins is considered to be a cornerstone of AKI prevention, there is a relative paucity of data supporting this approach.…”

Quality improvement goals for pediatric acute kidney injury: pediatric applications of the 22nd Acute Disease Quality Initiative (ADQI) conference

“…In fact, many of these quality improvement metrics were first developed and used in pediatric programs. Pediatric providers have been leaders in the development of quality improvement projects to reduce harm [26][27][28]48]. Today, there are over 40 pediatric hospitals that are using these metrics to track quality improvement efforts to reduce hospital-acquired nephrotoxic medication associated with AKI as part of the Solutions for Patient Safety collaborative.…”