Skip to main content
Top
Published in: Pediatric Drugs 3/2015

01-06-2015 | Original Research Article

Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review

Authors: Daniel Rainkie, Mary H. H. Ensom, Roxane Carr

Published in: Pediatric Drugs | Issue 3/2015

Login to get access

Abstract

Background

Pediatric studies and anecdotal experience suggest that current empiric vancomycin dosing does not reach serum trough concentration targets of at least 10 mg/L for uncomplicated infections or 15–20 mg/L for serious or complicated infections.

Objectives

This study reviewed vancomycin dosing and serum concentrations to (i) determine the proportion of patients who reached initial target concentrations; (ii) describe pharmacokinetic parameters; and (iii) compare patient-specific area-under-the-curve (AUC) values to population estimates using the Rodvold equation.

Methods

Following ethics approval, data were extracted from medical records of 200 patients aged 1 month–18 years, who received intravenous (IV) vancomycin and had at least two pharmacokinetically evaluable serum concentrations.

Results

Trough vancomycin concentrations of 10–15 and 15–20 mg/L were achieved in 25 (29 %) and 2 (2 %) patients receiving vancomycin 15 mg/kg IV every 6 h (q6 h) and 22 (20 %) and 9 (8 %) patients receiving vancomycin 20 mg/kg IV every 8 h (q8 h), respectively. Patients were stratified into four age groups (1 month–1 year, 1–6 years, 6–13 years and 13–18 years). Median (IQR) pharmacokinetic parameters were elimination rate constant 0.25 (0.09), 0.29 (0.07), 0.24 (0.10) and 0.22 (0.07) h−1; volume of distribution 0.56 (0.20), 0.61 (0.21), 0.47 (0.26) and 0.49 (0.22) L/kg; and half-life 2.8 (1.1), 2.4 (0.5), 2.9 (1.1) and 3.2 (1.0) h, respectively. Median (IQR) AUCs were 458 (170), 338 (132), 478 (215) and 513 (179) mg h/L and population-estimated AUCs were 67 (44), 108 (70), 299 (102) and 454 (103) mg h/L (p < 0.05 for all groups).

Conclusions

Based on these findings, we recommend vancomycin 70 and 90 mg/kg/day divided q6 h for troughs of 10–15 and 15–20 mg/L, respectively (patients 1 month–6 years) and 60 mg/kg/day divided q8 h and 70 mg/kg/day divided q6 h, respectively (patients >6 years) to undergo further testing as initial dosing regimens. Furthermore, population estimates grossly underestimate vancomycin AUC in patients 1–18 years old and thus patient-specific parameters are required.
Literature
1.
go back to reference Purcell K, Fergie J. Epidemic of community-acquired methicillin-resistant Staphylococcus aureus infections: a 14-year study at Driscoll Children’s Hospital. Arch Pediatr Adolesc Med. 2005;159(10):980–5.PubMedCrossRef Purcell K, Fergie J. Epidemic of community-acquired methicillin-resistant Staphylococcus aureus infections: a 14-year study at Driscoll Children’s Hospital. Arch Pediatr Adolesc Med. 2005;159(10):980–5.PubMedCrossRef
4.
go back to reference Ebert S, Leggett J, Vogelman B. In vivo cidal activity and pharmacokinetics parameters (PKPs) for vancomycin against methicillin-susceptible (MSSA) and -resistant (MRSA) S.aureus. In: Program and abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy (New York). Washington: American Society for Microbiology; 1987. p. 173. Ebert S, Leggett J, Vogelman B. In vivo cidal activity and pharmacokinetics parameters (PKPs) for vancomycin against methicillin-susceptible (MSSA) and -resistant (MRSA) S.aureus. In: Program and abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy (New York). Washington: American Society for Microbiology; 1987. p. 173.
5.
go back to reference Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82–98.PubMedCrossRef Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82–98.PubMedCrossRef
6.
go back to reference Lamer C, De Beco V, Soler P, Calvat S, Fagon JY, Dombret MC, et al. Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. Antimicrob Agents Chemother. 1993;37(2):281–6.PubMedCentralPubMedCrossRef Lamer C, De Beco V, Soler P, Calvat S, Fagon JY, Dombret MC, et al. Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. Antimicrob Agents Chemother. 1993;37(2):281–6.PubMedCentralPubMedCrossRef
7.
go back to reference Klugman KP, Friedland IR, Bradley JS. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother. 1995;39(9):1988–92.PubMedCentralPubMedCrossRef Klugman KP, Friedland IR, Bradley JS. Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in cerebrospinal fluid of children with acute bacterial meningitis. Antimicrob Agents Chemother. 1995;39(9):1988–92.PubMedCentralPubMedCrossRef
8.
go back to reference Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986;11(4):257–82.PubMedCrossRef Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986;11(4):257–82.PubMedCrossRef
9.
go back to reference Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-Resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–55.PubMedCrossRef Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-Resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–55.PubMedCrossRef
10.
go back to reference Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925–42.PubMedCrossRef Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925–42.PubMedCrossRef
11.
go back to reference Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O’Sullivan MVN, et al. Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2013;57(4):1654–63.PubMedCentralPubMedCrossRef Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O’Sullivan MVN, et al. Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2013;57(4):1654–63.PubMedCentralPubMedCrossRef
12.
go back to reference Eiland LS, English TM, Eiland EH 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;45(5):582–9.PubMedCrossRef Eiland LS, English TM, Eiland EH 3rd. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother. 2011;45(5):582–9.PubMedCrossRef
13.
go back to reference Frymoyer A, Hersh AL, Benet LZ, Gugliemo BJ. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J. 2009;28(5):398–402.PubMedCentralPubMedCrossRef Frymoyer A, Hersh AL, Benet LZ, Gugliemo BJ. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J. 2009;28(5):398–402.PubMedCentralPubMedCrossRef
14.
go back to reference Esau R, editor. Therapeutic drug monitoring: pediatric drug dosage guidelines. 6th ed. Vancouver (British Columbia): Department of Pharmacy, Children’s and Women’s Health Centre of B.C.; 2012. p. 295. Esau R, editor. Therapeutic drug monitoring: pediatric drug dosage guidelines. 6th ed. Vancouver (British Columbia): Department of Pharmacy, Children’s and Women’s Health Centre of B.C.; 2012. p. 295.
16.
go back to reference Rodvold KA, Blum RA, Fischer JH, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother. 1988;32(6):848–52.PubMedCentralPubMedCrossRef Rodvold KA, Blum RA, Fischer JH, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother. 1988;32(6):848–52.PubMedCentralPubMedCrossRef
18.
go back to reference Lwanga SK, Lemeshow S. Sample size determination in health studies: a practical manual. England: WHO; 1991. Lwanga SK, Lemeshow S. Sample size determination in health studies: a practical manual. England: WHO; 1991.
19.
go back to reference Benner KW, Worthington MA, Kimberlin DW, Hill K, Buckley K, Tofil NM. Correlation of vancomycin dosing to serum concentrations in pediatric patients: a retrospective database review. J Pediatr Pharmacol Ther. 2009;14(2):86–93.PubMedCentralPubMed Benner KW, Worthington MA, Kimberlin DW, Hill K, Buckley K, Tofil NM. Correlation of vancomycin dosing to serum concentrations in pediatric patients: a retrospective database review. J Pediatr Pharmacol Ther. 2009;14(2):86–93.PubMedCentralPubMed
20.
go back to reference ICH Expert Working Group. ICH Harmonised Tripartite Guideline: clinical investigation of medicinal products in the pediatric population E11. 2000. ICH Expert Working Group. ICH Harmonised Tripartite Guideline: clinical investigation of medicinal products in the pediatric population E11. 2000.
21.
go back to reference Carr R, Ensom MHH. Drug disposition and therapy in adolescence: the effects of puberty. J Pediatr Pharmacol Ther. 2003;8(2):86–96.PubMedCentralPubMed Carr R, Ensom MHH. Drug disposition and therapy in adolescence: the effects of puberty. J Pediatr Pharmacol Ther. 2003;8(2):86–96.PubMedCentralPubMed
22.
go back to reference Hayton WL. Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS PharmSci. 2000;2(1):E3.PubMed Hayton WL. Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS PharmSci. 2000;2(1):E3.PubMed
23.
go back to reference Madigan T, Sieve RM, Graner KK, Banerjee R. The effect of age and weight on vancomycin serum trough concentrations in pediatric patients. Pharmacotherapy. 2013;33:1264–72.PubMedCrossRef Madigan T, Sieve RM, Graner KK, Banerjee R. The effect of age and weight on vancomycin serum trough concentrations in pediatric patients. Pharmacotherapy. 2013;33:1264–72.PubMedCrossRef
24.
go back to reference Frymoyer A, Gugliemo BJ, Hersh AL. Desired vancomycin trough serum concentration for treating invasive methicillin-resistant staphylococcal infections. Pediatr Infect Dis. 2013;32:1077–9.CrossRef Frymoyer A, Gugliemo BJ, Hersh AL. Desired vancomycin trough serum concentration for treating invasive methicillin-resistant staphylococcal infections. Pediatr Infect Dis. 2013;32:1077–9.CrossRef
25.
go back to reference Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, et al. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013;32:e155–63.PubMedCentralPubMedCrossRef Le J, Bradley JS, Murray W, Romanowski GL, Tran TT, Nguyen N, et al. Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J. 2013;32:e155–63.PubMedCentralPubMedCrossRef
26.
go back to reference Camaione L, Elliott K, Mitchell-Van Steele A, Lomaestro B, Pai MP. Vancomycin dosing in children and young adults: back to the drawing board. Pharmacotherapy. 2013;33:1278–87.PubMedCrossRef Camaione L, Elliott K, Mitchell-Van Steele A, Lomaestro B, Pai MP. Vancomycin dosing in children and young adults: back to the drawing board. Pharmacotherapy. 2013;33:1278–87.PubMedCrossRef
27.
go back to reference Suzuki Y, Kawasaki K, Sato Y, Tokimatsu I, Itoh H, Hiramatsu K, et al. Is peak concentration needed in therapeutic drug monitoring of vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant Staphylococcus aureus pneumonia. Chemotherapy. 2012;58:308–12.PubMedCrossRef Suzuki Y, Kawasaki K, Sato Y, Tokimatsu I, Itoh H, Hiramatsu K, et al. Is peak concentration needed in therapeutic drug monitoring of vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant Staphylococcus aureus pneumonia. Chemotherapy. 2012;58:308–12.PubMedCrossRef
28.
go back to reference van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57(2):734–44.PubMedCentralPubMedCrossRef van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57(2):734–44.PubMedCentralPubMedCrossRef
Metadata
Title
Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review
Authors
Daniel Rainkie
Mary H. H. Ensom
Roxane Carr
Publication date
01-06-2015
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 3/2015
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.1007/s40272-015-0122-8

Other articles of this Issue 3/2015

Pediatric Drugs 3/2015 Go to the issue