Lower Vancomycin Serum Trough Concentrations Might Not Be the Answer

Abstract

To the Editors: We read with interest the article published by Frymoyer et al1 regarding desired vancomycin trough serum concentrations for treating invasive methicillin-resistant staphylococcal (MRSA) infections. In their article, the authors suggest that vancomycin serum trough concentrations of 7–10 μg/mL should be sufficient for treatment of invasive MRSA infection in more than 90% of children when the minimal inhibitory concentration of vancomycin is 1.0 μg/mL or less. The revelation that the current clinical practice guidelines by the Infectious Disease Society of America could be so misguided in recommending vancomycin serum trough concentrations of 15–20 μg/mL for the treatment of invasive MRSA seemed astonishing.2 We recently performed a validation study of a pediatric population pharmacokinetic model of vancomycin at our institution. Hospitalized children, 0–18 years of age, receiving vancomycin therapy were invited to participate. Subjects had 2 additional vancomycin serum concentrations drawn (peak and random) in addition to troughs obtained as part of clinical care and at the discretion of the physician. A previously published pediatric population pharmacokinetic model was validated in our population using Bayesian estimation in MW/Pharm (Mediware, Groningen, The Netherlands).3 Of 15 subjects enrolled, 12 subjects had vancomycin peak, random and trough serum concentrations obtained. A 24-hour area under the curve (AUC 24) was calculated to correspond with the serum concentrations in these subjects.4 While the simulation by Frymoyer et al1 was performed using a 25 kg base patient, our subjects’ weights ranged from 12.3 to 52.5 kg and encompassed children aged 1.2–17.3 years. Fifty-eight percentage of the subjects were boys, and the actual dosage range around the time of the vancomycin serum trough concentration ranged from 45 to 102 mg/kg/d. Two subjects who had a vancomycin serum trough concentration < 5 μg/mL had a corresponding AUC 24 ≤ 280. The 4 subjects who had a vancomycin serum trough concentration ≥ 14.5 μg/mL had a corresponding AUC 24 > 694. Only 67% of the remaining subjects with a vancomycin serum trough concentration between 8 and 10 μg/mL had a corresponding AUC 24 >400. This is important, as data from adults suggest that successful treatment is less likely if the ratio of AUC/minimal inhibitory concentration < 400.5 While the study published by Frymoyer et al1 brings up important topics for discussion, we would not recommend a change in clinical practice that simply sought lower vancomycin serum trough values. Instead, personalizing medical treatment and using information about the AUC and the minimal inhibitory concentration for each person requiring vancomycin for invasive staphylococcal disease could provide the best outcomes for our patients. Andrea Hahn, MD Division of Infectious Disease Alexander A. Vinks, PhD, PharmD Division of Clinical Pharmacology Cincinnati Children’s Hospital Medical Center Department of Pediatrics University of Cincinnati College of Medicine Cincinnati, OH