Skip Navigation



JAC Advance Access published online on June 2, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh268
© 2004 by The British Society for Antimicrobial Chemotherapy
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
54/1/199    most recent
dkh268v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Buijk, S. E.
Right arrow Articles by Bruining, H. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buijk, S. E.
Right arrow Articles by Bruining, H. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received December 7, 2003
Revised March 17, 2004
Accepted April 6, 2004

Original article

Perioperative pharmacokinetics of cefotaxime in serum and bile during continuous and intermittent infusion in liver transplant patients

S. E. Buijk 1*, I. C. Gyssens 2, J. W. Mouton 3, H. J. Metselaar 4, T. H. Groenland 5, H. A. Verbrugh 6, H. A. Bruining 1

1 Department of Surgery, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
2 Department of Medical Microbiology and Infectious Diseases, Department of Internal Medicine, Division of Infectious Diseases, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
3 Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, Department of Medical Microbiology & Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
4 Department of Hepatology and Gastroenterology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
5 Department of Anaesthesiology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
6 Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands

* To whom correspondence should be addressed. E-mail: stevenbuijk{at}hotmail.com.


  Abstract

Background: Drug pharmacokinetics may be altered during liver transplantation. Cefotaxime (CTX), used as perioperative prophylaxis, demonstrates time-dependent killing and therefore continuous infusion might have pharmacodynamic advantages.

Objectives: To determine the pharmacokinetics of CTX and desacetylcefotaxime (DCTX) in serum, bile and urine during continuous and intermittent infusion when performing liver transplantation.

Methods: Fifteen patients undergoing liver transplantation were studied after continuous infusion (CI) (4000 mg iv per 24 h following a loading dose of 1000 mg) and intermittent bolus infusion (BI) (1000 mg iv four times daily). Samples were collected during the first 48 h after liver transplantation. Concentrations of CTX and DCTX were determined by HPLC.

Results: During surgery, the mean concentration in serum after CI was 18 mg/L. The lowest serum concentration was 5 mg/L in the CI group and levels were undetectable in the BI group. Target serum concentrations of ≥4 mg/L were reached for 100% of the dosing interval during CI and ~60% during BI. Post-operatively, the mean concentration in serum after CI was 26 mg/L. The lowest serum concentration was 8 mg/L in the CI group and levels were undetectable after BI. The peroperative pharmacokinetics of CTX in this patient group were deranged and variable, mainly caused by an increased volume of distribution and decreased hepatic clearance. Metabolism was hampered, but DCTX area under the curve (AUC)/CTX AUC ratios varying between 0.7-0.9 were reached peroperatively. Post-operatively, DCTX AUC/CTX AUC ratios were higher (1.1-1.4). Unchanged CTX in bile was ~0.1% of the administered dose, leading to concentrations >4 mg/L throughout the dosing interval for both regimens.

Conclusion: Although an intermittent bolus infusion of CTX 1000 mg produces t > target concentration for 60% of the dosing interval during liver transplantation, serum concentrations may be insufficient during the reperfusion phase. Continuous infusion overcomes this. Post-operatively, CTX clearance is impaired by decreased metabolic clearance and there is substantial accumulation of DCTX. In bile, sufficient concentrations of CTX and its active metabolite are reached with both regimens.

Key Words: Keywords: antibiotics, critical care, surgery, pharmacodynamics, desacetylcefotaxime


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
P. Seguin, M. C. Verdier, C. Chanavaz, C. Engrand, B. Laviolle, P.-Y. Donnio, and Y. Malledant
Plasma and peritoneal concentration following continuous infusion of cefotaxime in patients with secondary peritonitis
J. Antimicrob. Chemother., March 1, 2009; 63(3): 564 - 567.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.