Continued Acute Kidney Injury in Children After 7 Days of Vancomycin Therapy

INTRODUCTION: Vancomycin is a commonly used antibacterial agent that has been associated with acute

kidney injury (AKI) in adults and children. An association between elevated trough concentrations and AKI in both adults and children has been demonstrated. The objective of this study was to determine the incidence and factors associated with continued AKI in a cohort of children categorized as having AKI within the first 7 days of vancomycin therapy.

METHODS: Children ages 1 through 18 years at a free-standing pediatric hospital, who experienced AKI within the first 7 days of their vancomycin course (from January through December of 2007 and 2010) were previously identified and evaluated. This follow-up study specifically examined those patients with AKI to evaluate continued AKI in patients receiving at least 8 days of vancomycin therapy. Patients were included if they received intravenous (IV) vancomycin for at least 72 hours for suspected or proven Gram-positive infection. Serum creatinine and trough concentrations were collected from day 8 of vancomycin therapy through 10 days following vancomycin discontinuation. AKI was defined as an increase in serum creatinine concentration by ≥50% from baseline values. Continued AKI was defined as any AKI identified beyond the first 7

days of treatment.

RESULTS : At total of 164 patients at a median (interquartile [IQR]) age of 2 (1-9) years with AKI identified within the first 7 days of vancomycin therapy were evaluated. Patients received a mean±SD empiric vancomycin dose of 43.3±15.5 mg/kg/day. Fifty patients (30%) received vancomycin for at least 8 days, and 12 patients (24%) met criteria for long-term AKI. Trough serum concentrations were obtained in 36 patients (72%) after at least 8 days of vancomycin therapy, with a median (IQR) vancomycin trough serum concentration of 11.3 (8-13.9) mg/L. In patients receiving at least 8 days of vancomycin therapy, continued AKI developed in 33.3% versus 25% (p=0.599) of patients with and without any serum trough concentration ≥15 mg/L, respectively. There were no differences in median (IQR) vancomycin trough concentrations between those with and without continued AKI (10.9 [IQR, 10.2-13.9] and 11.6 [IQR, 7.4-14]), respectively; p=0.855]. Rates of intensive care unit admission did not differ between patients with and those without continued AKI (22.9% vs. 26.7%, respectively; p=0.773).

CONCLUSIONS: Continued AKI occurred in 24% of children who were initially identified as having AKI within the first 7 days of vancomycin therapy and also received vancomycin therapy for at least 8 days. These findings raise additional questions about the indicative value of changes in serum creatinine concentration observed early in the vancomycin course for predicting continued AKI.