Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 23 , ISSUE 11 ( November, 2019 ) > List of Articles

Original Article

Steady-state Pharmacokinetics of Vancomycin in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Referral Center

Nitin B Mali, Milind S Tullu, Poorwa P Wandalkar, Siddharth P Deshpande, Vinod C Ingale, Nithya J Gogtay, Urmila M Thatte

Keywords : Gram-positive bacterial infection, Liquid chromatography mass spectrometry, Pediatric intensive care unit, Pharmacokinetics–pharmacodynamics, Vancomycin

Citation Information : Mali NB, Tullu MS, Wandalkar PP, Deshpande SP, Ingale VC, Gogtay NJ, Thatte UM. Steady-state Pharmacokinetics of Vancomycin in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Referral Center. Indian J Crit Care Med 2019; 23 (11):497-502.

DOI: 10.5005/jp-journals-10071-23275

License: CC BY-NC 4.0

Published Online: 01-08-2019

Copyright Statement:  Copyright © 2019; The Author(s).


Aims and objectives: Vancomycin is a drug of choice for various gram-positive bacterial (GPB) infections and is largely prescribed to pediatric intensive care unit (PICU) patients. Despite the different pathophysiology of these patients, limited data are available on pharmacokinetics of vancomycin. There are lack of data for critically ill Indian children; hence, study was conducted to assess the steady-state pharmacokinetics in children admitted to PICU. Materials and methods: Twelve subjects (seven males, five females) aged 1–12 years were enrolled. Vancomycin (dose of 20 mg/kg per 8 hours) was infused for over 1 hour and steady-state pharmacokinetics was performed on day 3. Vancomycin concentrations were measured by the validated liquid chromatography mass spectrometry method. Pharmacokinetic parameters were calculated using Winnonlin (Version 6.3; Pharsight, St. Louis, MO). Results: The steady-state mean Cssmax was 40.94 μg/mL (±15.07), and mean AUC0–8 hours was 124.15 μg/mL (±51.27). The mean t1/2 was 4.82 hours (±2.71), Vd was 12.48 L (±4.43), and Cl was 2.08 mL/minute (±0.89). The mean AUC0–24 among 12 subjects was 372.44 μg/mL (±153.82). Among 35 measured trough concentrations, 23 (65.71%) were below, 11 (31.43%) were within, and 1 (2.86%) was above the recommended range. Conclusion: The pharmacokinetic parameters of vancomycin were comparable with previously reported studies. However, recommended trough levels (10–20 μg/mL) were not achievable with current recommended dosing of 60 mg/kg/day.

  1. Grohskopf LA, Huskins WC, Sinkowitz-Cochran RL, Levine GL, Goldmann DA, Jarvis WR. Use of antimicrobial agents in United States neonatal and pediatric intensive care patients. Pediatr Infect Dis J 2005;24(9):766–773. DOI: 10.1097/01.inf.0000178064.55193.1c.
  2. Kepenekli E, Soysal A, Yalindag-Ozturk N, Ozgur O, Ozcan I, Devrim I, et al. Healthcare-associated infections in pediatric intensive care units in Turkey: a national point-prevalence survey. Jpn J Infect Dis 2015;68(5):381–386. DOI: 10.7883/yoken.JJID.2014.385.
  3. Abbas Q, Haq AU, Kumar R, Ali SA, Hussain K, Shakoor S. Evaluation of antibiotic use in pediatric intensive care unit of a developing country. Indian J Crit Care Med 2016;20(5):291–294. DOI: 10.4103/0972-5229.182197.
  4. Keyserling HL, Sinkowitz-Cochran RL, Harris II JM, Levine GL, Siegel JD, Stover BH, et al. Vancomycin use in hospitalized pediatric patients. Pediatrics 2003;112(2):e104–e111. DOI: 10.1542/peds.112.2.e104.
  5. Vazquez-Guillamet C, Kollef MH. Treatment of Gram-positive infections in critically ill patients. BMC Infect Dis 2014;14:92. DOI: 10.1186/1471-2334-14-92.
  6. Rivera AM, Boucher HW. Current concepts in antimicrobial therapy against select Gram-positive organisms: methicillin-resistant Staphylococcus aureus, penicillin-resistant Pneumococci, and vancomycin-resistant enterococci. Mayo Clin Proc 2011;86(12): 1230–1243. DOI: 10.4065/mcp.2011.0514.
  7. Bruniera FR, Ferreira FM, Saviolli LRM, Bacci MR, Feder D, Pedreira MDLG, et al. The use of vancomycin with its therapeutic and adverse effects: a review. Eur Rev Med Pharmacol Sci 2015;19(4):694–700.
  8. Rybak M, Lomaestro B, Rotschafer JC, Moellering Jr R, 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. DOI: 10.2146/ajhp080434.
  9. Vandecasteele SJ, De Vriese AS, Tacconelli E. The pharmacokinetics and pharmacodynamics of vancomycin in clinical practice: evidence and uncertainties. J Antimicrob Chemother 2013;68(4):743–748. DOI: 10.1093/jac/dks495.
  10. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, 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): 285–292. DOI: 10.1093/cid/cir034.
  11. Mali NB, Deshpande SP, Tullu MS, Deshmukh CT, Gogtay NJ, Thatte UM. A prospective antibacterial utilization study in pediatric intensive care unit of a tertiary referral center. Indian J Crit Care Med 2018;22(6):422–426. DOI: 10.4103/ijccm.IJCCM_365_17.
  12. Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2).
  13. Food and Drug Administration. Guidance for Industry: Bioanalytical method validation. [Internet]. 2001. Available from:
  14. Zhang T, Watson DG, Azike C, Tettey JNA, Stearns AT, Binning AR, et al. Determination of vancomycin in serum by liquid chromatography-high resolution full scan mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2007;857(2):352–356. DOI: 10.1016/j.jchromb.2007.07.041.
  15. Gabrielsson J, Weiner D. Non-compartmental analysis. Methods Mol Biol 2012;929:377–389. DOI: 10.1007/978-1-62703-050-2_16.
  16. Blot S, Koulenti D, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, et al. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study. Crit Care 2014;18(3):R99. DOI: 10.1186/cc13874.
  17. Matzke GR, Kovarik JM, Rybak MJ, Boike SC. Evaluation of the vancomycin clearance: creatinine-clearance relationship for predicting vancomycin dosage. Clin Pharm 1985;4(3):311–315.
  18. Marinho DS, Huf G, Ferreira BL, Castro H, Rodrigues CR, de Sousa VP, et al. The study of vancomycin use and its adverse reactions associated to patients of a Brazilian university hospital. BMC Res Notes 2011;4:236. DOI: 10.1186/1756-0500-4-236.
  19. Reis AG, Grisi SJ. Adverse effects of vancomycin in children: a review of 22 cases. Sao Paulo Med J 1997;115(3):1452–1455. DOI: 10.1590/S1516-31801997000300010.
  20. Safarnavadeh T, Rezaee S, Dashti-Khavidaki S, Khalili H, Daneshjoo K, Sadrai S, et al. Steady-state pharmacokinetic analysis of vancomycin in Iranian pediatric patients. DARU J Pharm Sci 2009;17:124–130.
  21. Gous AG, Dance MD, Lipman J, Luyt DK, Mathivha R, Scribante J. Changes in vancomycin pharmacokinetics in critically ill infants. Anaesth Intensive Care 1995;23(6):678–682. DOI: 10.1177/0310057X9502300603.
  22. Abdel Hadi O, Al Omar S, Nazer LH, Mubarak S, Le J. Vancomycin pharmacokinetics and predicted dosage requirements in pediatric cancer patients. J Oncol Pharm Pract 2015;22(3):448–453. DOI: 10.1177/1078155215591386.
  23. Chang D. Influence of malignancy on the pharmacokinetics of vancomycin in infants and children. Pediatr Infect Dis J 1995;14(8):667–673. DOI: 10.1097/00006454-199508000-00004.
  24. Krivoy N, Peleg S, Postovsky S, Ben Arush MW. Pharmacokinetic analysis of vancomycin in steady-state in pediatric cancer patients. Pediatr Hematol Oncol 1998;15(4):333–338. DOI: 10.3109/08880019809014017.
  25. Polard E, Le Bouquin A, Le Corre P, Kérebel C, Trout H, Feuillu A, et al. Non steady state PKS bayasian forecasting and vancomycin pharmacokinetics in ICU adult patients. Ther Drug Monit 1999;21(4):365–403. DOI: 10.1097/00007691-199908000-00003.
  26. Harada H, Miyagawa S, Kawasaki S, Hayashi K, Kitamura H, Katsuyama Y, et al. Study of the pharmacokinetics of vancomycin in patients with impaired liver function. J Infect Chemother 1999;5:104–107. DOI: 10.1007/s101560050018.
  27. Brown N, Ho D, Fong K, Bogerd L, Maksymiuk A, Bolivar R, et al. Effects of hepatic function on vancomycin clinical pharmacology. Antimicrob Agents Chemother 1983;23(4):603–609. DOI: 10.1128/AAC.23.4.603.
  28. Chhim RF, Arnold SR, Lee KR. Vancomycin dosing practices, trough concentrations, and predicted area under the curve in children with suspected invasive staphylococcal infections. J Pediatric Infect Dis Soc 2013;2(3):259–262. DOI: 10.1093/jpids/pis083.
  29. Hwang D, Chiu NC, Chang L, Peng CC, Huang DTN, Huang FY, et al. Vancomycin dosing and target attainment in children. J Microbiol Immunol Infect 2017;50(4):494–499. DOI: 10.1016/j.jmii.2015.08.027.
  30. Frymoyer A, Guglielmo BJ, Wilson SD, Scarpace SB, Benet LZ, Hersh AL. Impact of a hospitalwide increase in empiric pediatric vancomycin dosing on initial trough concentrations. Pharmacotherapy 2011;31(9):871–876. DOI: 10.1592/phco.31.9.871.
  31. Arfa P, Karimi A, Tabatabaei SR, Fahimzad A, Armin S, Sistanizad M. A prospective study to assess vancomycin serum concentrations in pediatric patients with current dosing guidelines. Iran J Pharm Res 2016;15(1):341–346.
  32. Buckel WR, Ghobrial S, Tamma PD, Milstone AM, Zhao Y, Hsu AJ. Risk factors for non-therapeutic initial steady-state vancomycin trough concentrations in children and adolescents receiving high empiric doses of intravenous vancomycin. Pediatr Drugs 2017;19(1):43–51. DOI: 10.1007/s40272-016-0202-4.
  33. Miloslavsky M, Galler MF, Moawad I, Actis J, Cummings BM, El Saleeby CM. The impact of pediatric-specific vancomycin dosing guidelines: a quality improvement initiative. Pediatrics 2017;139(6):e20162423. DOI: 10.1542/peds.2016-2423.
  34. Eiland LS, English TM, Eiland EH. Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients. Ann Pharmacother 2011;45(5):582–589. DOI: 10.1345/aph.1P588.
  35. Durham SH, Simmons ML, Mulherin DW, Foland JA. An evaluation of vancomycin dosing for complicated infections in pediatric patients. Hosp Pediatr 2015;5(5):276–281. DOI: 10.1542/hpeds.2014-0081.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.