Antimicrobial Reports
Clinical Evaluation of Vancomycin Dosage in Pediatric Oncology Patients Stefan J.W.J. Sanders, PharmD,* Yuma A. Bijleveld, PharmD,* Fleur Sinkeler, BSc,* Elles M. Kemper, PharmD, PhD,* Dasja Pajkrt, MD, PhD, MBA,† Marianne van de Wetering, MD, PhD,‡ Natasha K.A. van Eijkelenburg, MD,‡ and Ron A.A. Mathôt, PharmD, PhD* Abstract: Vancomycin trough serum concentrations were below therapeutic range (8–15 mg/L) in 58% of 124 pediatric oncology patients receiving 60 mg/kg/d divided qid. Patients 12 years. A vancomycin dosage of 60 mg/kg/d is inadequate for pediatric oncology patients >12 years. Key Words: vancomycin, pediatric oncology, serum concentrations (Pediatr Infect Dis J 2014;33:731–733)
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ediatric oncology patients with febrile neutropenia need to be treated with broad spectrum antibiotics to decrease morbidity and mortality due to infections. Gram-positive bacteria are the most frequently occurring causative microorganisms of fever in these patients; coagulase-negative Staphylococci are most common.1 Vancomycin is empirically initiated for Gram-positive coverage. Administering a dosage that produces adequate exposure directly upon start of therapy is crucial.2 In previous studies in pediatric oncology, patients trough concentrations have been evaluated after administration of a vancomycin dosage of 40 mg/kg/d.2–4 In these studies, it was however demonstrated that pediatric oncology patients need higher vancomycin dosages to attain comparable trough concentrations than peers without cancer due to an increase of clearance.3,4 Chang et al2 and more recently Piro et al5 suggested a dosage of 60 mg/kg/d for pediatric oncology patients to achieve target trough concentrations of 5–15 mg/L. This dosage is currently recommended for treatment of neutropenia in Dutch vancomycin guidelines for children. In adults, the clinical efficacy of vancomycin has been evaluated by the ratio of area under the came/minimal inhibitory concentration (AUC/MIC) that is preferably >400 hours.6 For pediatric patients, the usefulness of this pharmacodynamic parameter is currently investigated but has not been validated yet.7,8 Nevertheless, in clinical practice, a minimal trough concentration of 4–5 times MIC is generally used as a target for effective therapy. In the Dutch guideline for therapeutic drug monitoring of vancomycin in both adults and children, a trough concentration of 8–15 mg/L was considered therapeutic at the time of research. The objectives of this study were to evaluate if a dosage of 60 mg/kg/d qid leads to adequate vancomycin trough concentrations in pediatric oncology patients and to identify patient characteristics associated with subtherapeutic trough concentrations. Accepted for publication December 16, 2013. From the *Department of Clinical Pharmacy; †Department of Pediatric Infectious Diseases; and ‡Department of Pediatric Oncology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Ron A.A. Mathôt, PharmD, PhD, Department of Clinical Pharmacy, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3307-0731 DOI: 10.1097/INF.0000000000000268
MATERIALS AND METHODS In this retrospective study, all hospitalized pediatric oncology patients treated with vancomycin between January 2005 and December 2009 in our tertiary care academic children’s hospital were reviewed. Inclusion criteria were: children
Clinical Evaluation of Vancomycin Dosage in Pediatric Oncology Patients Stefan J.W.J. Sanders, PharmD,* Yuma A. Bijleveld, PharmD,* Fleur Sinkeler, BSc,* Elles M. Kemper, PharmD, PhD,* Dasja Pajkrt, MD, PhD, MBA,† Marianne van de Wetering, MD, PhD,‡ Natasha K.A. van Eijkelenburg, MD,‡ and Ron A.A. Mathôt, PharmD, PhD* Abstract: Vancomycin trough serum concentrations were below therapeutic range (8–15 mg/L) in 58% of 124 pediatric oncology patients receiving 60 mg/kg/d divided qid. Patients 12 years. A vancomycin dosage of 60 mg/kg/d is inadequate for pediatric oncology patients >12 years. Key Words: vancomycin, pediatric oncology, serum concentrations (Pediatr Infect Dis J 2014;33:731–733)
P
ediatric oncology patients with febrile neutropenia need to be treated with broad spectrum antibiotics to decrease morbidity and mortality due to infections. Gram-positive bacteria are the most frequently occurring causative microorganisms of fever in these patients; coagulase-negative Staphylococci are most common.1 Vancomycin is empirically initiated for Gram-positive coverage. Administering a dosage that produces adequate exposure directly upon start of therapy is crucial.2 In previous studies in pediatric oncology, patients trough concentrations have been evaluated after administration of a vancomycin dosage of 40 mg/kg/d.2–4 In these studies, it was however demonstrated that pediatric oncology patients need higher vancomycin dosages to attain comparable trough concentrations than peers without cancer due to an increase of clearance.3,4 Chang et al2 and more recently Piro et al5 suggested a dosage of 60 mg/kg/d for pediatric oncology patients to achieve target trough concentrations of 5–15 mg/L. This dosage is currently recommended for treatment of neutropenia in Dutch vancomycin guidelines for children. In adults, the clinical efficacy of vancomycin has been evaluated by the ratio of area under the came/minimal inhibitory concentration (AUC/MIC) that is preferably >400 hours.6 For pediatric patients, the usefulness of this pharmacodynamic parameter is currently investigated but has not been validated yet.7,8 Nevertheless, in clinical practice, a minimal trough concentration of 4–5 times MIC is generally used as a target for effective therapy. In the Dutch guideline for therapeutic drug monitoring of vancomycin in both adults and children, a trough concentration of 8–15 mg/L was considered therapeutic at the time of research. The objectives of this study were to evaluate if a dosage of 60 mg/kg/d qid leads to adequate vancomycin trough concentrations in pediatric oncology patients and to identify patient characteristics associated with subtherapeutic trough concentrations. Accepted for publication December 16, 2013. From the *Department of Clinical Pharmacy; †Department of Pediatric Infectious Diseases; and ‡Department of Pediatric Oncology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Ron A.A. Mathôt, PharmD, PhD, Department of Clinical Pharmacy, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3307-0731 DOI: 10.1097/INF.0000000000000268
MATERIALS AND METHODS In this retrospective study, all hospitalized pediatric oncology patients treated with vancomycin between January 2005 and December 2009 in our tertiary care academic children’s hospital were reviewed. Inclusion criteria were: children
