Late Occurring Vancomycin-associated Acute Kidney Injury in Children Receiving Prolonged Therapy

Background: Vancomycin-associated acute kidney injury (AKI) has been associated with trough concentrations ≥ 15 mg/L and vancomycin duration in adults and children. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving ≥ 8 days of vancomycin therapy.

Methods: Medical records of children aged 30 days through 17 years who received vancomycin for at least 72 hours between January - December of 2007 and 2010 were identified and reviewed. Available serum creatinine and trough concentrations obtained from start of vancomycin therapy through 10 days after vancomycin discontinuation were recorded. Early AKI was categorized as occurring within the first 7 days of vancomycin therapy. Late AKI was categorized as AKI occurring after the first 7 days of treatment and within 48 hours of vancomycin receipt.

Results: Eight hundred and forty-six children (N = 846) with median age 3 years were included. Early AKI occurred in 19.4% (164/846); those patients were excluded from further analysis. Vancomycin duration ≥ 8 days was observed in 29.5% (201/682) of remaining children; 167 had available serum creatinine data. Late AKI occurred in 12.6% (21/167). Admission to an acute care service was associated with late AKI (21.9% vs. 6.8%, p = 0.004). Late AKI patients maintained a median (IQR) vancomycin trough concentration (mg/L) of 10.1 (7.3 - 12.5) compared to 8.6 (6.7 - 11.3) in patients with no AKI (p = 0.188). Late AKI developed more frequently in patients receiving vancomycin for 15 days or greater (20% vs. 8.9%, p = .043). Patients who received vancomycin in combination with piperacillin/tazobactam and either IV acyclovir or amphotericin experienced increased late AKI (44.4% vs. 10.8%, p = .016; and 50% vs. 11.2%, p = .027; respectively).

Conclusions: Late AKI occurred in nearly 13% of children receiving ≥ 8 days of vancomycin therapy. There appear to be no clinically important associations between vancomycin trough levels and late AKI, but longer vancomycin duration may confer higher risk. There remains need for prospective study of vancomycin-associated AKI risk assessment tools.