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. 1996 Jan;40(1):139–145. doi: 10.1128/aac.40.1.139

Clinical pharmacokinetics of piperacillin-tazobactam combination in patients with major burns and signs of infection.

P Bourget 1, A Lesne-Hulin 1, R Le Reveillé 1, H Le Bever 1, H Carsin 1
PMCID: PMC163072  PMID: 8787895

Abstract

The pathophysiology associated with major burns is complex and subject to a state of flux. The combination of beta-lactamase inhibitors with powerful penicillins is an interesting and an attractive potential solution to the emergence of bacterial resistance. The kinetics in serum and urine and the clinical safety of a fixed combination of 4 g of piperacillin (PPR) and 0.5 g of tazobactam (TZB) were studied in 10 patients (22 to 50 years old and weighing 45 to 105 kg) with major burns who were infected with Pseudomonas aeruginosa and various entero-bacteria. All of them received additional antimicrobial drugs. Treatment involved one dose every 6 h. The mean body surface area affected by third-degree burns was 30.0% +/- 4.0%. The study took place in accordance with current ethical guidelines. Two series of blood samples were drawn after the first (day 1) and ninth (day 3 at steady state) doses; urine was collected during the same periods. Levels of PPR and TZB in serum and urine were measured by high-pressure liquid chromatography. A noncompartmental method was used for kinetic and graphic analysis of concentration-time pairs. The safety of the treatment was excellent. There was no systemic accumulation of the beta-lactam combination. Residual concentrations measured on days 1 and 3 [mean (standard error of the mean)] were above the MIC for the organism responsible for infection; i.e., C(min)day1 = 26.3 (8.5) and C(min)day3 = 21.0 (9.1) for PPR and C(min)day1 = 1.9 (0.6) and C(min)day3 = 1.4 (0.3) for TZB. There was no statistically significant difference between pharmacokinetic parameters determined for day 1 and day 3. Evidence was found in burn patients, in contrast to healthy subjects, of a marked increase in apparent volumes of distribution, in such a way that the apparent elimination half-lives of the combination were notably prolonged, i.e., 1.8 (0.3) versus 1.5 (0.3) h for PPR in patients and healthy subjects, respectively, and 1.7 (0.3) versus 1.4 (0.3) h for TZB. These findings indicate the possibility of nonrenal translesional diffusion of PPR-TZB in burn patients. The polarity of the association would further support this hypothesis. It has been shown here that the recommended dosage regimen for administration of PPR-TZB must be high in major-burn patients, i.e., 4 g/0.5 g every 6 h. The data obtained provide valuable information, which is suitable for immediate application in everyday clinical practice.

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Selected References

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

  1. Benet L. Z., Galeazzi R. L. Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci. 1979 Aug;68(8):1071–1074. doi: 10.1002/jps.2600680845. [DOI] [PubMed] [Google Scholar]
  2. Bloedow D. C., Hansbrough J. F., Hardin T., Simons M. Postburn serum drug binding and serum protein concentrations. J Clin Pharmacol. 1986 Feb;26(2):147–151. doi: 10.1002/j.1552-4604.1986.tb02923.x. [DOI] [PubMed] [Google Scholar]
  3. Boucher B. A., Hickerson W. L., Kuhl D. A., Bombassaro A. M., Jaresko G. S. Imipenem pharmacokinetics in patients with burns. Clin Pharmacol Ther. 1990 Aug;48(2):130–137. doi: 10.1038/clpt.1990.127. [DOI] [PubMed] [Google Scholar]
  4. Colburn W. A. Estimating the accumulation of drugs. J Pharm Sci. 1983 Jul;72(7):833–834. doi: 10.1002/jps.2600720734. [DOI] [PubMed] [Google Scholar]
  5. Friedrich L. V., White R. L., Kays M. B., Brundage D. M., Yarbrough D., 3rd Aztreonam pharmacokinetics in burn patients. Antimicrob Agents Chemother. 1991 Jan;35(1):57–61. doi: 10.1128/aac.35.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gutmann L., Kitzis M. D., Yamabe S., Acar J. F. Comparative evaluation of a new beta-lactamase inhibitor, YTR 830, combined with different beta-lactam antibiotics against bacteria harboring known beta-lactamases. Antimicrob Agents Chemother. 1986 May;29(5):955–957. doi: 10.1128/aac.29.5.955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kinzig M., Sörgel F., Brismar B., Nord C. E. Pharmacokinetics and tissue penetration of tazobactam and piperacillin in patients undergoing colorectal surgery. Antimicrob Agents Chemother. 1992 Sep;36(9):1997–2004. doi: 10.1128/aac.36.9.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Martyn J. Clinical pharmacology and drug therapy in the burned patient. Anesthesiology. 1986 Jul;65(1):67–75. doi: 10.1097/00000542-198607000-00011. [DOI] [PubMed] [Google Scholar]
  9. Marunaka T., Maniwa M., Matsushima E., Minami Y. High-performance liquid chromatographic determination of a new beta-lactamase inhibitor and its metabolite in combination therapy with piperacillin in biological materials. J Chromatogr. 1988 Sep 23;431(1):87–101. doi: 10.1016/s0378-4347(00)83072-8. [DOI] [PubMed] [Google Scholar]
  10. Polk R. E., Mayhall C. G., Smith J., Hall G., Kline B. J., Swensson E., Haynes B. W. Gentamicin and tobramycin penetration into burn eschar. Pharmacokinetics and microbiological effects. Arch Surg. 1983 Mar;118(3):295–302. doi: 10.1001/archsurg.1983.01390030027005. [DOI] [PubMed] [Google Scholar]
  11. Potel G., Meignier M., Baron D., Reynaud A., Touze M. D., Courtieu A. L. Pharmacokinetics of fosfomycin in normal and burn patients. Effect of probenecid. Drugs Exp Clin Res. 1989;15(4):177–184. [PubMed] [Google Scholar]
  12. Sawchuk R. J., Zaske D. E. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. J Pharmacokinet Biopharm. 1976 Apr;4(2):183–195. doi: 10.1007/BF01086153. [DOI] [PubMed] [Google Scholar]
  13. Walstad R. A., Aanderud L., Thurmann-Nielsen E. Pharmacokinetics and tissue concentrations of ceftazidime in burn patients. Eur J Clin Pharmacol. 1988;35(5):543–549. doi: 10.1007/BF00558251. [DOI] [PubMed] [Google Scholar]
  14. Wise R., Logan M., Cooper M., Andrews J. M. Pharmacokinetics and tissue penetration of tazobactam administered alone and with piperacillin. Antimicrob Agents Chemother. 1991 Jun;35(6):1081–1084. doi: 10.1128/aac.35.6.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Yamaoka K., Nakagawa T., Uno T. Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm. 1978 Dec;6(6):547–558. doi: 10.1007/BF01062109. [DOI] [PubMed] [Google Scholar]
  16. Zaske D. E., Sawchuk R. J., Strate R. G. The necessity of increased doses of amikacin in burn patients. Surgery. 1978 Nov;84(5):603–608. [PubMed] [Google Scholar]

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