Clinical Pharmacokinetics

, Volume 33, Issue 1, pp 32–51 | Cite as

Pharmacokinetics and Administration Regimens of Vancomycin in Neonates, Infants and Children

  • Keith A. RodvoldEmail author
  • Julie A. Everett
  • Randy D. Pryka
  • Donna M. Kraus
Review Article Special Populations


The increased use of vancomycin in neonatal and paediatric patients has prompted numerous pharmacokinetic studies and the development of many empirical administration methods. The majority of dosage guidelines use the relationship between pharmacokinetic parameters and patient variables such as chronological age, body weight, and/or measures of renal function. Currently, those dosage guidelines which are based upon postconceptional age and body weight seem to provide the best options for empirical administration in neonates and infants. In addition, serum creatinine may prove to be a useful guide to the empirical administration of vancomycin in neonates older than 7 to 14 days.

Several investigators have reported the individualisation of dosage regimens based on pharmacokinetic-based administration methods. The most common techniques employed have been Sawchuk-Zaske method and Bayesian forecasting. However, only a limited number of studies have evaluated either empirical administration or individualised administration techniques in patient populations outside those of the original reports; this makes choosing between the methods difficult.

Pharmacokinetic data and administration recommendations have gradually become available in special paediatric patient populations. The majority of studies have focused on patients requiring cardiopulmonary bypass surgery or with burns, cancer or central nervous system infections. However, a limited amount of information is available regarding vancomycin disposition in children older than 1 year of age with and without end-stage renal failure.

The monitoring of serum vancomycin concentrations may be useful in selected neonatal and paediatric patient populations, especially where large interpatient variability occurs and administration guidelines are not clearly established. Similar to the literature on adults, the lack of conclusive evidence concerning the relationship between serum vancomycin concentrations and therapeutic responses leaves this topic open to debate.


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  1. 1.
    Spears RL, Koch R. The use of vancomycin in pediatrics. Antibiotics Ann 1959–1960: 798–803Google Scholar
  2. 2.
    Schaad UB, McCracken GH, Nelson JD. Clinical pharmacology and efficacy of vancomycin in pediatric patients. J Pediatr 1980; 96: 119–26PubMedCrossRefGoogle Scholar
  3. 3.
    Kaplan EL. Vancomycin in infants and children: a review of pharmacology and indications for therapy and prophylaxis. J Antimicrob Chemother 1984; 14 Suppl. D: 59–66PubMedCrossRefGoogle Scholar
  4. 4.
    de Louvois J, Harvey D. Antibiotic therapy of the newborn. Clin Perinatol 1988; 15: 365–89PubMedGoogle Scholar
  5. 5.
    Hall SL. Coagulase-negative staphylococcal infections in neonates. Pediatr Infect Dis J 1991; 10: 57–67PubMedCrossRefGoogle Scholar
  6. 6.
    Patrick CC. Coagulase-negative staphylococci: pathogens with increasing clinical significance. J Pediatr 1990; 116: 497–507PubMedCrossRefGoogle Scholar
  7. 7.
    Battisti O, Mitchison R, Davies PA. Changing blood culture isolates in a referral neonatal intensive care unit. Arch Dis Child 1981; 56: 775–8PubMedCrossRefGoogle Scholar
  8. 8.
    Hoogkamp-Korstanje KJ, Cats B, Senders RC, et al. Analysis of bacterial infections in a neonatal intensive care unit. J Hosp Infect 1982; 3: 275–84PubMedCrossRefGoogle Scholar
  9. 9.
    Hack M, Horbar JD, Malloy MH, et al. Very low birth weight outcomes of the national institute of child health and human development neonatal network. Pediatrics 1991; 87: 587–97PubMedGoogle Scholar
  10. 10.
    Becerra JE, Fry YW, Rowley DL. Morbidity estimates of conditions originating in the perinatal period: United States, 1986 through 1987. Pediatrics 1991; 88: 553–9PubMedGoogle Scholar
  11. 11.
    Edwards MS, Baker CJ. Median sternotomy wound infections in children. Pediatr Infect Dis J 1983; 2: 105–9CrossRefGoogle Scholar
  12. 12.
    Scherer LR, West KW, Weber TR, et al. Staphylococcus epidermidis sepsis in pediatric patients: clinical and therapeutic considerations. J Pediatr Surg 1984; 19: 358–61PubMedCrossRefGoogle Scholar
  13. 13.
    Siegel JD, McCracken GH. Sepsis neonatorum. N Engl J Med 1981; 304: 642–7PubMedCrossRefGoogle Scholar
  14. 14.
    Friedman LE, Brown AE, Miller DR, et al. Staphylococcus epidermidis septicemia in children with leukemia and lymphoma. Am J Dis Child 1984; 138: 715–9PubMedGoogle Scholar
  15. 15.
    Pryka RD, Rodvold KA, Erdman SM. An updated comparison of drug dosing methods: Part IV: vancomycin. Clin Pharmacokine 1991; 20: 463–76CrossRefGoogle Scholar
  16. 16.
    Leader WG, Chandler MHH, Castiglia M. Pharmacokinetic optimisation of vancomycin therapy. Clin Pharmacokinet 1995; 28: 327–42PubMedCrossRefGoogle Scholar
  17. 17.
    Cantu TG, Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis 1994; 18: 533–43PubMedCrossRefGoogle Scholar
  18. 18.
    Moellering RC. Monitoring serum vancomycin levels: climbing the mountain because it is there? Clin Infect Dis 1994; 18: 544–6PubMedCrossRefGoogle Scholar
  19. 19.
    Pryka RD. Vancomycin serum concentration monitoring: a continued debate. Ann Pharmacother 1994; 28: 1397–9PubMedGoogle Scholar
  20. 20.
    Saunders NJ. Vancomycin administration and monitoring reappraisal. J Antimicrob Chemother 1995; 36: 279–82PubMedCrossRefGoogle Scholar
  21. 21.
    Wandstrat TL, Phelps SJ. Vancomycin dosing in neonatal patients: the controversy continues. Neonatal Netw 1994; 13: 33–9PubMedGoogle Scholar
  22. 22.
    Morse GD, Nairn DK, Bertino JS, et al. Overestimation of vancomycin concentrations utilizing fluorescence polarization immunoassay in patients on peritoneal dialysis. Ther Drug Monit 1987; 9: 212–5PubMedCrossRefGoogle Scholar
  23. 23.
    Anne L, Hu M, Chan K, et al. Potential problem with fluorescence polarization immunoassay cross-reactivity to vancomycin degradation product CDP-1: its detection in sera of renally impaired patients. Ther Drug Monit 1989; 11: 585–91PubMedCrossRefGoogle Scholar
  24. 24.
    Hu MW, Anne L, Forni T, et al. Measurement of vancomycin in renally impaired patient samples using a new high-performance liquid chromatography method with vitamin B12 internal standard: comparison of high-performance liquid chromatography, EMIT, and fluorescence polarization immunoassay. Ther Drug Monit 1990; 12: 562–9PubMedCrossRefGoogle Scholar
  25. 25.
    White LO, Edwards R, Holt HA, et al. The in-vitro degradation at 37°C of vancomycin in serum, CAPD fluid and phosphate-buffered saline. J Antimicrob Chemother 1988; 22: 739–45PubMedCrossRefGoogle Scholar
  26. 26.
    Harris CM, Kopecka H, Harris TM. Vancomycin: structure and transformation to CDP-1. J Am Chem Soc 1983; 105: 6915–22CrossRefGoogle Scholar
  27. 27.
    Paap CM, Sharpe GL. Overestimation of serum vancomycin concentrations using a fluorescence polarization immunoassay (TDx) in preterm neonates. Dev Pharmacol Ther 1993; 20: 174–9PubMedGoogle Scholar
  28. 28.
    Alpert G, Campos JM, Harris MC, et al. Vancomycin dosage in pediatrics reconsidered. Am J Dis Child 1984; 138: 20–2PubMedGoogle Scholar
  29. 29.
    Bailie GR, Ackerman BH, Fischer J, et al. Increased vancomycin dosage requirements in young burn patients. J Burn Care Rehabil 1984; 5: 376–8CrossRefGoogle Scholar
  30. 30.
    Gross JR, Kaplan SL, Kramer WG, et al. Vancomycin pharmacokinetics in premature infants. Pediatr Pharmacol 1985; 5: 17–22Google Scholar
  31. 31.
    Amaker RD, DiPiro JT. Bhatia J. Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 1996; 40: 1139–42PubMedGoogle Scholar
  32. 32.
    Armstrong DK, Hidalgo HA, Eldadah M. Vancomycin and tobramycin clearance in an infant during continous hemofiltration. Ann Pharmacother 1993; 27: 224–7PubMedGoogle Scholar
  33. 33.
    Asbury WH, Darsey EH, Rose WB, et al. Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation. Ann Pharmacother 1993; 27: 490–6PubMedGoogle Scholar
  34. 34.
    Chang D, Liem L, Malogolowkin M. A prospective study of vancomycin pharmacokinetics and dosage requirements in pediatric cancer patients. Pediatr Infect Dis J 1994; 13; 969–74PubMedCrossRefGoogle Scholar
  35. 35.
    Chang D. Influence of malignancy on the pharmacokinetics of vancomycin in infants and children. Pediatr Infect Dis J 1995; 14; 667–73PubMedCrossRefGoogle Scholar
  36. 36.
    Gabriel MH, Kildoo CW, Gennrich JL, et al. Prospective evaluation of a vancomycin dosage guidelines for neonates. Clin Pharm 1991; 10: 129–32PubMedGoogle Scholar
  37. 37.
    Hatzopoulos FK, Stile-Calligaro IL, Rodvold KA, et al. Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery. Pediatr Infect Dis J 1993; 12: 300–4PubMedCrossRefGoogle Scholar
  38. 38.
    Hoie EB, Swigart SA, Leuschen MP, et al. Vancomycin pharmacokinetics in infants undergoing extracorporeal membrane oxygenation. Clin Pharm 1990; 9: 711–5PubMedGoogle Scholar
  39. 39.
    Jarrett RV, Marinkovich GA, Gayle EL, et al. Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants. Pediatr Infect Dis J 1991; 12: 156–7Google Scholar
  40. 40.
    Kildoo CW, Lin ML, Gabriel MH, et al. Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine. Dev Pharmacol Ther 1990; 14: 77–83Google Scholar
  41. 41.
    Koren G, James A. Vancomycin dosing in preterm infants: prospective verification of new dosing recommendation. J Pediatr 1987; 110: 797–8PubMedCrossRefGoogle Scholar
  42. 42.
    Leonard MB, Koren G, Stevenson DK, et al. Vancomycin pharmacokinetics in very low birth weight neonates. Pediatr Infect Dis J 1989; 8: 282–6PubMedGoogle Scholar
  43. 43.
    Lisby-Sutch SM, Nahata MC. Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants. Eur J Clin Pharmacol 1988; 35: 637–42PubMedCrossRefGoogle Scholar
  44. 44.
    McDougal A, Ling EW, Levine M. Vancomycin pharmacokinetics and dosing in premature neonates. Ther Drug Monit 1995; 17: 319–26PubMedCrossRefGoogle Scholar
  45. 45.
    Moller JC, Nachtrodt G, Tegtmeyer FK, et al. Prophylactic low-dose vancomycin treatment in very-low-birth-weight infants. Dev Pharmacol Ther 1992; 19: 178–82PubMedGoogle Scholar
  46. 46.
    Reed MD, Kliegman RM, Weiner JS, et al. The clinical pharmacology of vancomycin in seriously ill preterm infants. Pediatr Res 1987; 22: 360–3PubMedCrossRefGoogle Scholar
  47. 47.
    Rodvold KA, Gentry CA, Plank G, et al. Bayesian forecasting of serum vancomycin concentrations in neonates and infants. Ther Drug Monit 1995; 17: 239–46PubMedCrossRefGoogle Scholar
  48. 48.
    Schaible DH, Rocci ML, Alpert GA, et al. Vancomycin pharmacokinetics in infants: relationships to indices of maturation. Pediatr Infect Dis J 1986; 5: 304–8CrossRefGoogle Scholar
  49. 49.
    Seay RE, Brundage RC, Jensen PD, et al. Population pharmacokinetics of vancomycin in neonates. Clin Pharmacol Ther 1994; 56: 169–75PubMedCrossRefGoogle Scholar
  50. 50.
    Naqvi SH, Keenan WJ, Reichley RM, et al. Vancomycin pharmacokinetics in small, seriously ill infants. Am J Dis Child 1986; 140: 107–10PubMedGoogle Scholar
  51. 51.
    James A, Koren G, Milliken J, et al. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother 1987; 31: 52–4PubMedCrossRefGoogle Scholar
  52. 52.
    Riley HD, Ryan NJ. Treatment of severe staphylococcal infection in infancy and childhood with vancomycin. Antibiotic Ann 1959–1960: 908–16Google Scholar
  53. 53.
    Rodvold KA, Erdman SM, Pryka RD. Vancomycin. In: Schumacher GE, editor. Therapeutic drug monitoring. Norwalk: Appleton & Lange, 1996: 587–664Google Scholar
  54. 54.
    Schaad UB, Nelson JD, McCracken GH. Pharmacology and efficacy of vancomycin for staphylococcal infections in children. Rev Infect Dis 1981; 3 Suppl.: 282–8CrossRefGoogle Scholar
  55. 55.
    Levy M, Koren G, Dupuis L, et al. Vancomycin-induced red man syndrome. Pediatrics 1990; 86: 572–80PubMedGoogle Scholar
  56. 56.
    Odio C, Mohs E, Sklar FH, et al. Adverse reactions to vancomycin used as prophylaxis for CSF shunt procedures. Am J Dis Child 1984; 138: 17–9PubMedGoogle Scholar
  57. 57.
    Boussemart T, Cardona J, Bertheir M, et al. Cardiac arrest associated with vancomycin in a neonate [letter]. Arch Dis Child Fetal Neonatal 1995; 73: 123CrossRefGoogle Scholar
  58. 58.
    Best CJ, Ewart M, Sumner E. Perioperative complications following the use of vancomycin in children: a report of two cases. Br J Anaesth 1989; 62: 576–7PubMedCrossRefGoogle Scholar
  59. 59.
    Mayhew JF, Deutsch S. Cardiac arrest following administration of vancomycin. Can Anaesth Soc J 1985; 32: 65–6PubMedCrossRefGoogle Scholar
  60. 60.
    Bergeron L, Boucher FD. Possible red-man syndrome associated with systemic absorption of oral vancomycin in a child with normal renal function. Ann Pharmacother 1994; 28: 581–4PubMedGoogle Scholar
  61. 61.
    Burkhart KK, Metcalf S, Shurnas E, et al. Exchange transfusion and multidose activated charcoal following vancomycin overdose. Clin Toxicol 1992; 30: 285–94CrossRefGoogle Scholar
  62. 62.
    Linder N, Edwards R, McClead R, et al. Safety of vancomycin with or without gentamicin in neonates. Neonatal Netw 1993; 12: 27–30PubMedGoogle Scholar
  63. 63.
    Odio C, McCracken GH, Nelson JD. Nephrotoxicity associated with vancomycin-aminoglycoside therapy in four children. J Pediatr 1984; 105: 491–3PubMedCrossRefGoogle Scholar
  64. 64.
    Dean RP, Wagner DJ, Tolpin MD. Vancomycin/aminoglycoside nephrotoxicity [letter]. J Pediatr 1985; 106: 861–2PubMedGoogle Scholar
  65. 65.
    Tissing WJE, Umans-Eckenhausen MAW, van den Anker JN. Vancomycin intoxication in a preterm neonate [letter]. Eur J Pediatr 1993; 152: 700PubMedCrossRefGoogle Scholar
  66. 66.
    Goren MP, Baker DK, Shenep JL. Vancomycin does not enhance amikacin-induced tubular nephrotoxicity in children. Pediatr Infect Dis J 1989; 8: 278–82PubMedGoogle Scholar
  67. 67.
    Bolinger AM, So MH, Winter ME. Aminoglycoside and vancomycin pharmacokinetic monitoring in pediatric patients [letter]. Am J Hosp Pharm 1989; 46: 1770–1PubMedGoogle Scholar
  68. 68.
    Banner W, Ray CG. Vancomycin in perspective. Am J Dis Child 1984; 138: 14–6PubMedGoogle Scholar
  69. 69.
    Gous AGS, Dance MD, Lipman J, et al. Changes in vancomycin pharmacokinetics in critically ill infants. Anaesth Intensive Care 1995; 23: 678–82PubMedGoogle Scholar
  70. 70.
    Thompson CM, Long SS, Gilligan PH, et al. Absorption of oral vancomycin: possible associated toxicity. Int J Pediatr Nephrol 1983; 4: 1–4PubMedGoogle Scholar
  71. 71.
    Luer MS, Hatton J. Vancomycin administration into the cerebrospinal fluid: a review. Ann Pharmacother 1993; 27: 912–21PubMedGoogle Scholar
  72. 72.
    Fan-Havard P, Nahata MC, Bartowski MH, et al. Pharmacokinetics and cerebrospinal fluid (CSF) concentrations of vancomycin in pediatric patients undergoing CSF shunt placement. Chemotherapy 1990; 36: 103–8PubMedCrossRefGoogle Scholar
  73. 73.
    McGee SM, Kaplan SL, Mason EO. Ventricular fluid concentrations of vancomycin in children after intravenous and intraventricular administration. Pediatr Infect Dis J 1990; 9: 138–9PubMedCrossRefGoogle Scholar
  74. 74.
    Pau AK, Smego RA, Fisher MA. Intraventricular vancomycin: observations of tolerance and pharmacokinetics in two infants with ventricular shunt infections. Pediatr Infect Dis J 1986; 5: 93–6CrossRefGoogle Scholar
  75. 75.
    Isaac DW, Pearson TA, Hurwitz CA, et al. Clinical and microbiologic aspects of Staphylococcus haemolyticus infections. Pediatr Infect Dis J 1993; 12: 1018–21PubMedCrossRefGoogle Scholar
  76. 76.
    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: 1988–92PubMedCrossRefGoogle Scholar
  77. 77.
    Paris MM, Hickey SM, Uscher MI, et al. Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1994; 38: 1320–4PubMedCrossRefGoogle Scholar
  78. 78.
    Cabellos C, Martinez-Lacasa J, Martos A, et al. Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in experimental pneumococcal meningitis. Antimicrob Agents Chemother 1995; 39: 2158–60PubMedCrossRefGoogle Scholar
  79. 79.
    Bayston R, Hart CA, Barnicoat M. Intraventricular vancomycin in the treatment of ventriculitis associated with cerebrospinal fluid shunting and drainage. J Neurol Neurosurg Psychiatry 1987; 50: 1419–23PubMedCrossRefGoogle Scholar
  80. 80.
    McLaurin RL, Frame PT. Treatment of infections with cerebrospinal fluid shunts. Rev Infect Dis 1987; 9: 595–603PubMedCrossRefGoogle Scholar
  81. 81.
    Jacobs F, Delecluse F, Raftopoulos C, et al. Intraventricular vancomycin in CSF shunt infections. Neurosurgery 1987; 21: 112–3PubMedCrossRefGoogle Scholar
  82. 82.
    Arroyo JC, Quindlen EA. Accumulation of vancomycin after intraventricular infusions. South Med J 1983; 76: 1554–5PubMedCrossRefGoogle Scholar
  83. 83.
    Dagan O, Klein J, Gruenwald C, et al. Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs. Ther Drug Monit 1993; 15: 263–6PubMedCrossRefGoogle Scholar
  84. 84.
    Spivey JM, Gal P. Vancomycin pharmacokinetics in neonates [letter]. Am J Dis Child 1986; 140: 859PubMedGoogle Scholar
  85. 85.
    Sawchuk RJ, Zaske DE. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. J Pharmacokinet Biopharm 1976; 4: 183–95PubMedGoogle Scholar
  86. 86.
    Murray WE. Vancomycin pharmacokinetics [letter]. Arch J Dis Child 1986; 140: 1096–7Google Scholar
  87. 87.
    Naqvi SH, Keenen W, Reichley R. Vancomycin pharmacokinetics in neonates [letter]. Am J Dis Child 1986; 140: 859Google Scholar
  88. 88.
    Baker D, Rotschafer JC, Sawchuk R, et al. Vancomycin pharmacokinetics [letter]. J Pediatr 1980; 97: 502–3PubMedCrossRefGoogle Scholar
  89. 89.
    Gabriel MH, Gennrich JL. Vancomycin dosing for neonates [letter]. Pediatr Infect Dis J 1993; 12: 705–6PubMedGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Keith A. Rodvold
    • 1
    Email author
  • Julie A. Everett
    • 2
  • Randy D. Pryka
    • 3
  • Donna M. Kraus
    • 1
  1. 1.m/c 886, Pharmacy Practice, College of Pharmacy, Room #164University of Illinios at ChicagoChicagoUSA
  2. 2.College of PharmacyPurdue UniversityWest LafayetteUSA
  3. 3.College of PharmacyUniversity of ToledoToledoUSA

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