Are Elevated Vancomycin Serum Trough Concentrations Achieved Within the First 7 Days of Therapy Associated With Acute Kidney Injury in Children?

Abstract

Background. In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development.Methods. Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic fibrosis, an elevated baseline serum creatinine, or without a serum creatinine concentration obtained after receipt of vancomycin were excluded. Acute kidney injury was defined using adapted pediatric RIFLE criteria as an increase in serum creatinine from baseline of 50% or more. BACKGROUNDVancomycin is commonly used in the pediatric population for empiric or targeted treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and has been associated with acute kidney injury (AKI) [1].Empiric intravenous (IV) vancomycin in children has traditionally been dosed as 40 mg/kg per day in 4 divided doses to achieve target serum trough concentrations of 5-10 mg/L. Recent evidence and recommendations suggest that such doses are unlikely to achieve the goal serum trough concentrations (10-20 mg/L) that are necessary for the optimal area under the curve (AUC) for plasma concentration relative to the organism minimum inhibitory concentration (MIC) (AUC/MIC) [2][3][4][5].

Frequency of and Risk Factors for Acute Kidney Injury Associated With Vancomycin Use in the Pediatric Intensive Care Unit

“…1 Estimates of the incidence of AKI associated with vancomycin in pediatrics range from 5% to 27.2%. [4][5][6][7][8][9] However, evidence is conflicting regarding the relationship between PICU admission, vancomycin use, and AKI. McKamy et al 4 studied children on vancomycin in all hospital wards (n = 167) and defined AKI as a 50% baseline increase in serum creatinine (SCr) or an increase of 0.5 mg/dL.…”

“…The PICU patients had a significantly higher (p < 0.001) frequency of AKI than those without a PICU stay; and trough concentrations of ≥ 15 mg/L in pediatric patients were associated with a threefold increased risk of developing AKI. Knoderer et al 5 studied children on vancomycin in all hospital wards (n = 859) and AKI was defined as meeting pRIFLE category I ( 5 Of note, studies have shown that there is no association between AKI and total daily dose of vancomycin, rather that the serum levels of vancomycin are the important factor in development of AKI. 4,5,7 Totapally et al 7 performed a retrospective analysis on PICU patients who received vancomycin for at least 3 days (n = 391 courses) with AKI defined as pRIFLE category I (Table 1) 9 reported that concurrent use of nephrotoxic medications, and longer duration of therapy were associated with increased odds of AKI (defined as pRIFLE category I; Table 1).…”

Antimicrobial Renal Injury in a Pediatric Intensive Care Unit: β-Lactams vs. Vancomycin

“…While there is much debate and perseveration regarding renal injury associated with vancomycin, our data from our previous [15] and current investigation suggests the incidence and risk is not greater than that associated with other β-lactam antimicrobials, which are commonly used in pediatric intensive care units and don't engender the same debate or concern for renal injury. As previously mentioned, there have been two investigations evaluating whether vancomycin trough levels are associated with renal injury across an entire pediatric population and three specifically evaluating varying pediatric ICU populations [14][15][16][17][18]. While ICU admission and vancomycin troughs ≥15 mcg/mL were identified as risk factors, thus far, none of the three investigations of pediatric ICU patients validate the finding of increased renal injury with vancomycin trough levels ≥15 mcg/mL [15,16,18].…”

“…The authors suggested that higher vancomycin troughs in addition to admission to the intensive care unit were potential risk factors for renal injury [15]. Similarly, Knoderer et al suggest that ICU admission and initial vancomycin trough levels ≥15 mcg/mL were associated with renal injury [17]. However, these studies did not address the relationship between the vancomycin trough concentrations and the incidence of renal injury in critically ill children Cies et al did attempt to quantify the incidence of vancomycin induced renal injury in a pediatric intensive care unit population between troughs ≥15 mcg/mL and troughs of 5-15 mcg/mL [15] and demonstrated there was not an increased incidence of vancomycin induced renal injury in a cohort of 113 patients that received vancomycin for at least 48 h [15].…”

“…The current adult literature suggests an increased incidence of renal injury with increasing vancomycin trough levels, especially when other risk factors are present including: intensive care unit admission, prolonged duration of vancomycin therapy, concurrent nephrotoxic medications, increased age, and obesity [6,[11][12][13]. There is some level of disagreement in the pediatric literature evaluating risk factors for renal injury with higher vancomycin trough concentrations as compared with the adult literature [6,[11][12][13][14][15][16][17][18].…”