Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Jul;36(7):1404–1411. doi: 10.1128/aac.36.7.1404

Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability.

F Bressolle 1, J E de la Coussaye 1, R Ayoub 1, D Fabre 1, R Gomeni 1, G Saissi 1, J J Eledjam 1, M Galtier 1
PMCID: PMC191594  PMID: 1510435

Abstract

Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations.

Full text

PDF
1406

Selected References

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

  1. Aguilera D., Coupry A., Holzapfel L., Karlin P., Carrère-Debat D., Giudicelli D. P., Gontier D. Etude des concentrations sériques et bronchiques au cours de l'administration continue de nétilmicine intratrachéale. Pathol Biol (Paris) 1986 Jun;34(5 Pt 2):657–662. [PubMed] [Google Scholar]
  2. Bergogne-Berezin E., Pierre J., Berthelot G., Kafe H., Even P., Gibert C., Safran D., Stern M. Diffusion bronchique des nouvelles beta-lactamines anti-pseudomonas. Signification clinique. Pathol Biol (Paris) 1984 May;32(5):421–425. [PubMed] [Google Scholar]
  3. Davies B. I., Maesen F. P., van Noord J. A. Treatment of chronic and recurrent respiratory infections with intramuscular ceftazidime. J Antimicrob Chemother. 1983 Jul;12 (Suppl A):1–8. doi: 10.1093/jac/12.suppl_a.1. [DOI] [PubMed] [Google Scholar]
  4. Erttmann M., Ullmann U., Koch E. M. Results of a clinical and pharmacokinetic study of ceftazidime in patients with postoperative pneumonia on assisted ventilation. J Hosp Infect. 1990 Apr;15 (Suppl A):55–59. doi: 10.1016/0195-6701(90)90080-8. [DOI] [PubMed] [Google Scholar]
  5. Fagon J. Y., Chastre J., Hance A. J., Guiguet M., Trouillet J. L., Domart Y., Pierre J., Gibert C. Detection of nosocomial lung infection in ventilated patients. Use of a protected specimen brush and quantitative culture techniques in 147 patients. Am Rev Respir Dis. 1988 Jul;138(1):110–116. doi: 10.1164/ajrccm/138.1.110. [DOI] [PubMed] [Google Scholar]
  6. Feeley T. W., Du Moulin G. C., Hedley-Whyte J., Bushnell L. S., Gilbert J. P., Feingold D. S. Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med. 1975 Sep 4;293(10):471–475. doi: 10.1056/NEJM197509042931003. [DOI] [PubMed] [Google Scholar]
  7. Greenfield S., Teres D., Bushnell L. S., Hedley-Whyte J., Feingold D. S. Prevention of gram-negative bacillary pneumonia using aerosol polymyxin as prophylaxis. I. Effect on the colonization pattern of the upper respiratory tract of seriously ill patients. J Clin Invest. 1973 Nov;52(11):2935–2940. doi: 10.1172/JCI107490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haley R. W., Culver D. H., White J. W., Morgan W. M., Emori T. G., Munn V. P., Hooton T. M. The efficacy of infection surveillance and control programs in preventing nosocomial infections in US hospitals. Am J Epidemiol. 1985 Feb;121(2):182–205. doi: 10.1093/oxfordjournals.aje.a113990. [DOI] [PubMed] [Google Scholar]
  9. Johanson W. G., Jr, Seidenfeld J. J., de los Santos R., Coalson J. J., Gomez P. Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents. Am Rev Respir Dis. 1988 Feb;137(2):265–272. doi: 10.1164/ajrccm/137.2.265. [DOI] [PubMed] [Google Scholar]
  10. Karhunen M., Koskela O., Hällström K. Single dose of tinidazole in prophylaxis in infections following vaginal surgery. J Antimicrob Chemother. 1981 Oct;8(4):283–290. doi: 10.1093/jac/8.4.283. [DOI] [PubMed] [Google Scholar]
  11. Kelly H. B., Menendez R., Fan L., Murphy S. Pharmacokinetics of tobramycin in cystic fibrosis. J Pediatr. 1982 Feb;100(2):318–321. doi: 10.1016/s0022-3476(82)80664-1. [DOI] [PubMed] [Google Scholar]
  12. Kercsmar C. M., Stern R. C., Reed M. D., Myers C. M., Murdell D., Blumer J. L. Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response. J Antimicrob Chemother. 1983 Jul;12 (Suppl A):289–295. doi: 10.1093/jac/12.suppl_a.289. [DOI] [PubMed] [Google Scholar]
  13. Klastersky J., Cappel R., Noterman J., Snoeck J., Geuning C., Mouawad E. Endotracheal gentamicin for the prevention of bronchial infections in patients with tracheotomy. Int J Clin Pharmacol. 1973 Jul;7(4):279–286. [PubMed] [Google Scholar]
  14. Klick J. M., du Moulin G. C., Hedley-Whyte J., Teres D., Bushnell L. S., Feingold D. S. Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients. J Clin Invest. 1975 Mar;55(3):514–519. doi: 10.1172/JCI107957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leroy A., Leguy F., Borsa F., Spencer G. R., Fillastre J. P., Humbert G. Pharmacokinetics of ceftazidime in normal and uremic subjects. Antimicrob Agents Chemother. 1984 May;25(5):638–642. doi: 10.1128/aac.25.5.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rubinstein E., Green M., Modan M., Amit P., Bernstein L., Rubinstein A. The effects of nosocomial infections on the length and costs of hospital stay. J Antimicrob Chemother. 1982 Jan;9 (Suppl A):93–100. doi: 10.1093/jac/9.suppl_a.93. [DOI] [PubMed] [Google Scholar]
  17. Strandvik B., Malmborg A. S., Alfredson H., Ericsson A. Clinical results and pharmacokinetics of ceftazidime treatment in patients with cystic fibrosis. J Antimicrob Chemother. 1983 Jul;12 (Suppl A):283–287. doi: 10.1093/jac/12.suppl_a.283. [DOI] [PubMed] [Google Scholar]
  18. Taburet A. M., Steimer J. L., Doucet D., Singlas E. Le temps de présence moyen dans l'organisme. Un nouveau paramètre pharmacocinétique?. Therapie. 1986 Jan-Feb;41(1):1–10. [PubMed] [Google Scholar]
  19. Turner A., Pedler S. J., Carswell F., Spencer G. R., Speller D. C. Serum and sputum concentrations of ceftazidime in patients with cystic fibrosis. J Antimicrob Chemother. 1984 Nov;14(5):521–527. doi: 10.1093/jac/14.5.521. [DOI] [PubMed] [Google Scholar]

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

RESOURCES