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

Abstract

Abstract:Background: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations ≥15 mg/L and longer therapy duration. 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: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy and within 48 hours following vancomycin discontinuation. The primary outcome was incidence of late AKI as determined by modified pRIFLE criteria. Results: One-hundred sixty-seven patients were included, with a median (interquartile range) age (years) and weight (kg) of 2 (1-7) and 12.5 (8.9-23.8). Late AKI was identified in 12.6% (21/167). A higher percentage of late AKI patients received concomitant treatment with intravenous acyclovir, amphotericin products, or piperacillin-tazobactam. Age <1 year was the only factor independently associated with late AKI development (odds ratio = 4.4; 95% confidence interval = 1.3-15.4). Conclusions: Late AKI occurred in nearly 13% of children receiving ≥8 days of vancomycin therapy. This study suggests that vancomycin trough concentrations are not associated with late AKI, but that age <1 year and concomitant administration of certain nephrotoxins may be factors associated with increased risk.

Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient

“…It is well documented that vancomycin is primarily renally eliminated, and adjustments in dose should occur for diminished kidney function. Prior publications have noted that age is a significant covariate for vancomycin pharmacokinetic disposition in the pediatric population, most likely due to extended courses of vancomycin and subsequent increases in SCR, but we did not identify this as a significant covariate (1,11).…”

Review of vancomycin-induced renal toxicity: an update

“…Similarly, there is a threefold greater occurrence of AKI when this combination was compared with the controls who were treated with a concurrent cefepime [Gomes et al 2014]. Furthermore, in a pediatric study, concurrent use of vancomycin with acyclovir, amphotericin B and piperacillin-tazobactam significantly increased the risk of AKI respectively [Knoderer et al 2015]. A major limitation of retrospective data is the uncertainty of the adverse renal impact while using other agents that were not part of the study.…”

“…Furthermore, there is fivefold higher incidence with a concurrent use of nephrotoxic drugs. Other notable determinants of VIN are critical illness, pretreatment kidney injury, and age less than 12 months [Knoderer et al 2015;Ragab et al 2013;Totapally et al 2013]. Nevertheless, AKI is often modest in degree and it is frequently reversible.…”

Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients

“…The length of admission was longer in the piperacillintazobactam group (13 [9][10][11][12][13][14][15] days vs cefepime 10 [6][7][8][9][10][11][12][13][14] days, P = 0.042), the duration of vancomycin and study antibiotics was similar in both groups (piperacillin-tazobactam 9 [6][7][8][9][10][11][12][13] days vs cefepime 10 [6-13] days, P = 0.454). Three patients in the cefepime group had pre-existing CF-related diabetes, but there were not any LECLEIR AND PETTIT | 1001 differences between the medications identified with potential for nephrotoxicity ( Table 1).…”

“…9 These results were confirmed in another study that found that 19.9% of patients, aged 3 (IQR 1-9) years, experienced nephrotoxicity after therapy with vancomycin for at least 72 h. 10 In a subsequent study completed by the same group, they retrospectively found an insignificant increase in late-occurring AKI with vancomycin and piperacillin/tazobactam (OR 2.77, 95%CI 0.97-7.9, P = 0.058). 11 In critically ill pediatric patients, however, multiple studies have not demonstrated an increase in acute kidney injury during vancomycin therapy. Cies and colleagues evaluated beta lactam monotherapy compared to combination therapy with vancomycin and did not find a statistically significant difference in the incidence of renal injury (8.8% vs 8.9%, P = 1) in a critically ill pediatric population, despite a mean vancomycin trough of 17.8 ±3.1 mcg/mL.…”