The Effectiveness of a Vancomycin Dosing Guideline in the Neonatal Intensive Care Unit for Achieving Goal Therapeutic Trough Concentrations

Abstract

Concern for bacterial resistance and treatment failure with vancomycin trough concentrations < 10 μg/mL have led guidelines to increase goal concentrations. There is a paucity of data evaluating vancomycin dosage necessary to achieve goals in the neonatal intensive care unit (NICU). We aimed to evaluate the implementation of a new vancomycin dosing guideline in improving trough target attainment. This retrospective study evaluated neonates in the NICU treated with vancomycin between January 2009 and December 2015. Therapeutic trough concentration attainment (10-20 μg/mL) was compared between neonates receiving vancomycin per old versus new dosing guidelines. Vancomycin trough concentrations, modeled pharmacodynamic target attainment, and nephrotoxicity were compared between groups. A total of 212 vancomycin trough concentrations (n = 91 old and n = 121 new guideline) were evaluated in 182 unique neonates. The mean ± standard deviation trough concentration achieved was 18.0 ± 7.3 μg/mL vs 8.9 ± 4.8 μg/mL in the new and old guidelines, respectively (P < .01). The new guideline resulted in a higher percentage of neonates achieving trough concentrations of 10 to 20 μg/mL (62% vs 29%; P < .01) and decreased the percentage of neonates with subtherapeutic trough concentrations (9% vs 69%; P < .01). Pharmacokinetic modeling identified postmenstrual age, days of life, and urine output as predictors of vancomycin clearance and resultant trough and area under the curve values (P < .01 for all). Trough concentrations >10 μg/mL ensured area under the curve /minimum inhibitory concentration >400 in >90% of neonates when bacteria minimum inhibitory concentration was ࣘ 1 μg/mL. Nephrotoxicity was similar between groups (8.3% vs 7.7%; P = .99). In conclusion, a vancomycin nomogram designed to achieve trough concentration of 10 to 20 μg/mL improves pharmacodynamic target attainment in neonates in the NICU.

Vancomycin-associated acute kidney injury epidemiology in children: a systematic review

“…Nine studies (45% of relevant studies; 1940 children) found an association between vancomycin levels and v-AKI 17 19 21 25 29 31 32 35 38. Eleven studies (55% of relevant studies; 3234 children) showed no association 16 18 20 26 28 30 32 34 36 37 39. A final vancomycin trough concentration above the local threshold of ≥15 mg/L was reported to be an independent risk factor for v-AKI in children in several studies19 25 29 31 38 and this was confirmed by Zhang et al in multivariate analysis 17.…”

“…This study includes a total of 12 730 paediatric patients with a median age of 2.5 years (range 0–23), and 57% were male patients. There was missing age17 18 and gender data19 20 in two studies each. The median dose of vancomycin was 43.3 mg/kg/day (range 14.9–60.0).…”

“…Two studies (20%), including 7270 patients, found an association between the dose of vancomycin and v-AKI 16 36. Eight studies (80% of papers retrieved; 1136 patients) did not find an association 20 25 26 28 29 31 37 38. In the study by Sinclair et al , the odds of nephrotoxicity increased by 16% for every additional 5 mg/kg of vancomycin (OR=1.11; 95% CI=1.01 to 1.22) and patients who received ≥80 mg/kg/day were 3.3 times more likely to develop AKI 36…”

“…The systematic review demonstrated that the median incidence of v-AKI was 11.8%16–40 (range 1.6–27.2) 22 34. Six specific risk factors were reported by two or more papers to be statistically significantly associated with v-AKI and are described as follows.…”

Vancomycin Prescribing Practices and Therapeutic Drug Monitoring for Critically Ill Neonatal and Pediatric Patients: A Survey of Physicians and Pharmacists in Hong Kong

“…The current landscape of multiple dose recommendations pose difficulties on the clinicians to determine dose that can achieve target AUC/MIC goals. This has led institutions to adopt their own measures of developing internal dosing recommendations based on clinical variables collected from their own specific patient population and through stimulation of real-world data (26,27). Recent studies have also demonstrated the value of using population pharmacokinetic data to personalize empirical vancomycin dosing.…”