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

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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.

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References

  1. 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.

    Article  PubMed  Google Scholar 

  2. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2010. Centers for Disease Control and Prevention; 2011 [Cited Aug 4/2012]. Available from: http://www.cdc.gov/abcs/reports-findings/survreports/spneu10.pdf.

  3. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2003. Centers for Disease Control and Prevention; 2004 [Cited Aug 4/2012]. Available from: http://www.cdc.gov/abcs/reports-findings/survreports/spneu03.pdf.

  4. 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. 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.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986;11(4):257–82.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  14. 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.

  15. Clinical Pharmacokinetics Service and Anticoagulation Guidelines. Davis GA, Lewis DA, editors, July 2010 (32nd ed) [Cited July 29/2012]. Available online at: http://www.hosp.uky.edu/pharmacy/formulary/criteria/Clinical_PKS_Manual-July_2010.pdf#page=100.

  16. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–37.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Lwanga SK, Lemeshow S. Sample size determination in health studies: a practical manual. England: WHO; 1991.

    Google Scholar 

  19. 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.

    PubMed Central  PubMed  Google Scholar 

  20. ICH Expert Working Group. ICH Harmonised Tripartite Guideline: clinical investigation of medicinal products in the pediatric population E11. 2000.

  21. Carr R, Ensom MHH. Drug disposition and therapy in adolescence: the effects of puberty. J Pediatr Pharmacol Ther. 2003;8(2):86–96.

    PubMed Central  PubMed  Google Scholar 

  22. Hayton WL. Maturation and growth of renal function: dosing renally cleared drugs in children. AAPS PharmSci. 2000;2(1):E3.

    CAS  PubMed  Google Scholar 

  23. 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.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  Google Scholar 

  25. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of interest

Daniel Rainkie has no conflicts of interest to declare. Mary H.H. Ensom has held grants (not related to the article) from the Canadian Society of Hospital Pharmacists Research and Education Foundation and Medisca, Inc. in the past 36 months. Roxane R. Carr has no conflicts of interest to declare.

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Authors and Affiliations

  1. Children’s and Women’s Health Centre of British Columbia, Vancouver, BC, Canada

    Daniel Rainkie & Mary H. H. Ensom

  2. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

    Daniel Rainkie, Mary H. H. Ensom & Roxane Carr

  3. Department of Pharmacy, Children’s and Women’s Health Centre of British Columbia, 4500 Oak Street Room 0B7, Vancouver, BC, V6H 3N1, Canada

    Roxane Carr

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  1. Daniel Rainkie
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  2. Mary H. H. Ensom
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  3. Roxane Carr
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Correspondence to Roxane Carr.

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Rainkie, D., Ensom, M.H.H. & Carr, R. Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review. Pediatr Drugs 17, 245–253 (2015). https://doi.org/10.1007/s40272-015-0122-8

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  • DOI: https://doi.org/10.1007/s40272-015-0122-8

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