Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 May;40(5):1139–1142. doi: 10.1128/aac.40.5.1139

Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation.

R D Amaker 1, J T DiPiro 1, J Bhatia 1
PMCID: PMC163279  PMID: 8723454

Abstract

Extracorporeal membrane oxygenation (ECMO) is a widely used therapy for neonates with respiratory failure. Because of sepsis, many of these infants require antibiotics like vancomycin during ECMO treatment. ECMO transiently alters renal function and increases the circulating blood volume by 75%. Initial vancomycin pharmacokinetics were determined in 12 infants undergoing ECMO to determine an adequate drug administration regimen. Vancomycin dosage was based on current recommendations for weight and gestational age. Pharmacokinetic parameters were determined by fitting the data to a two compartment model. This study yielded a mean steady-state volume of distribution of 1.1 +/- 0.5 (range, 0.6 to 2.1) liters/kg and a mean vancomycin clearance of 0.78 +/- 0.19 (range, 0.49 to 1.07) ml/min/kg. The mean vancomycin half-life was 16.9 +/- 9.5 (range, 8.8 to 42.9) h. Nomogram-calculated creatinine clearance was a significant predictor of vancomycin terminal rate constant and clearance. These data suggest alterations in the pharmacokinetics of vancomycin in infants on ECMO. With the goal of achieving vancomycin concentrations in serum above the MIC for the offending pathogen while using the least amount of the drug necessary, new administration guidelines for term infants without renal impairment undergoing ECMO should be 20 mg of vancomycin per kg at an interval of 24 h. With significant renal impairment, the interval should be extended on the basis of concentrations in serum. In comparison with previously published data, the neonates undergoing ECMO in our study demonstrated a much larger volume of distribution, a lower clearance, and consequently a longer vancomycin half-life.

Full Text

The Full Text of this article is available as a PDF (174.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adolph V., Ekelund C., Smith C., Starrett A., Falterman K., Arensman R. Developmental outcome of neonates treated with extracorporeal membrane oxygenation. J Pediatr Surg. 1990 Jan;25(1):43–46. doi: 10.1016/s0022-3468(05)80162-9. [DOI] [PubMed] [Google Scholar]
  2. Anderson H. L., 3rd, Coran A. G., Drongowski R. A., Ha H. J., Bartlett R. H. Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation. J Pediatr Surg. 1992 Aug;27(8):1003–1008. doi: 10.1016/0022-3468(92)90547-k. [DOI] [PubMed] [Google Scholar]
  3. Arant B. S., Jr Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr. 1978 May;92(5):705–712. doi: 10.1016/s0022-3476(78)80133-4. [DOI] [PubMed] [Google Scholar]
  4. Bartlett R. H., Gazzaniga A. B., Toomasian J., Coran A. G., Roloff D., Rucker R., Corwin A. G. Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg. 1986 Sep;204(3):236–245. doi: 10.1097/00000658-198609000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhatt-Mehta V., Johnson C. E., Schumacher R. E. Gentamicin pharmacokinetics in term neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy. 1992;12(1):28–32. [PubMed] [Google Scholar]
  6. Cohen P., Collart L., Prober C. G., Fischer A. F., Blaschke T. F. Gentamicin pharmacokinetics in neonates undergoing extracorporal membrane oxygenation. Pediatr Infect Dis J. 1990 Aug;9(8):562–566. doi: 10.1097/00006454-199008000-00007. [DOI] [PubMed] [Google Scholar]
  7. Hatzopoulos F. K., Stile-Calligaro I. L., Rodvold K. A., Sullivan-Bolyai J., Del Nido P., Levitsky S. Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery. Pediatr Infect Dis J. 1993 Apr;12(4):300–304. doi: 10.1097/00006454-199304000-00008. [DOI] [PubMed] [Google Scholar]
  8. Hoie E. B., Swigart S. A., Leuschen M. P., Willett L. D., Bolam D. L., Goodrich P. D., Bussey M. E., Nelson R. M., Jr Vancomycin pharmacokinetics in infants undergoing extracorporeal membrane oxygenation. Clin Pharm. 1990 Sep;9(9):711–715. [PubMed] [Google Scholar]
  9. Holley F. O., Ponganis K. V., Stanski D. R. Effect of cardiopulmonary bypass on the pharmacokinetics of drugs. Clin Pharmacokinet. 1982 May-Jun;7(3):234–251. doi: 10.2165/00003088-198207030-00004. [DOI] [PubMed] [Google Scholar]
  10. Many M., Soroff H. S., Birtwell W. C., Wise H. M., Deterling R. A., Jr The physiologic role fo pulsatile and nonpulsatile blood flow. 3. Effects of unilateral renal artery depulsation. Arch Surg. 1968 Dec;97(6):917–923. doi: 10.1001/archsurg.1968.01340060095010. [DOI] [PubMed] [Google Scholar]
  11. Matzke G. R., Zhanel G. G., Guay D. R. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986 Jul-Aug;11(4):257–282. doi: 10.2165/00003088-198611040-00001. [DOI] [PubMed] [Google Scholar]
  12. Naqvi S. H., Keenan W. J., Reichley R. M., Fortune K. P. Vancomycin pharmacokinetics in small, seriously ill infants. Am J Dis Child. 1986 Feb;140(2):107–110. doi: 10.1001/archpedi.1986.02140160025021. [DOI] [PubMed] [Google Scholar]
  13. Schaad U. B., McCracken G. H., Jr, Nelson J. D. Clinical pharmacology and efficacy of vancomycin in pediatric patients. J Pediatr. 1980 Jan;96(1):119–126. doi: 10.1016/s0022-3476(80)80347-7. [DOI] [PubMed] [Google Scholar]
  14. Schumacher R. E., Palmer T. W., Roloff D. W., LaClaire P. A., Bartlett R. H. Follow-up of infants treated with extracorporeal membrane oxygenation for newborn respiratory failure. Pediatrics. 1991 Apr;87(4):451–457. [PubMed] [Google Scholar]
  15. Schwartz G. J., Brion L. P., Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987 Jun;34(3):571–590. doi: 10.1016/s0031-3955(16)36251-4. [DOI] [PubMed] [Google Scholar]
  16. Southgate W. M., DiPiro J. T., Robertson A. F. Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 1989 Jun;33(6):817–819. doi: 10.1128/aac.33.6.817. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES