Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1987 Mar;31(3):398–403. doi: 10.1128/aac.31.3.398

Evaluation of combination chemotherapy in a lightly anesthetized animal model of Pseudomonas pneumonia.

F M Gordin, M G Rusnak, M A Sande
PMCID: PMC174740  PMID: 3107461

Abstract

Gram-negative bacillary pneumonia is a major cause of morbidity and mortality in hospitalized patients. The use of synergistic combinations of aminoglycosides and beta-lactams for therapy of this infection has been recommended but remains controversial. We designed a new model of Pseudomonas pneumonia in a lightly sedated guinea pig by using a long-acting anesthetic to impair natural respiratory defenses. We used this model to compare the efficacy of ceftazidime and tobramycin alone and in combination in the therapy of Pseudomonas pneumonia. The two antibiotics were shown to be synergistic in vitro for the strain of Pseudomonas aeruginosa tested. Treated animals receiving both antibiotics had fewer viable bacteria remaining in lung tissues (P less than 0.05) and exhibited a trend towards improved survival in comparison to animals receiving a single drug. In this model of Pseudomonas pneumonia, in vitro synergy was reflected by increased efficacy in vivo.

Full text

PDF
398

Images in this article

400Image
on p.400

Selected References

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

  1. Andriole V. T. Antibiotic synergy in experimental infection with Pseudomonas. II. The effect of carbenicillin, cephalothin, or cephanone combined with tobramycin or gentamicin. J Infect Dis. 1974 Feb;129(2):124–133. doi: 10.1093/infdis/129.2.124. [DOI] [PubMed] [Google Scholar]
  2. Baltch A. L., Hammer M., Smith R. P., Sutphen N. Pseudomonas aeruginosa bacteremia: susceptibility of 100 blood culture isolates to seven antimicrobial agents and its clinical significance. J Lab Clin Med. 1979 Aug;94(2):201–214. [PubMed] [Google Scholar]
  3. Bayer A. S., Norman D., Kim K. S. Efficacy of amikacin and ceftazidime in experimental aortic valve endocarditis due to Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1985 Dec;28(6):781–785. doi: 10.1128/aac.28.6.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berendt R. F., Long G. G., Abeles F. B., Canonico P. G., Elwell M. R., Powanda M. C. Pathogenesis of respiratory Klebsiella pneumoniae infection in rats: bacteriological and histological findings and metabolic alterations. Infect Immun. 1977 Feb;15(2):586–593. doi: 10.1128/iai.15.2.586-593.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bodey G. P., Feld R., Burgess M. A. Beta-lactam antibiotics alone or in combination with gentamicin for therapy of gram-negative bacillary infections in neutropenic patients. Am J Med Sci. 1976 Mar-Apr;271(2):179–186. doi: 10.1097/00000441-197603000-00006. [DOI] [PubMed] [Google Scholar]
  6. Chadwick E. G., Shulman S. T., Yogev R. Correlation of antibiotic synergy in vitro and in vivo: use of an animal model of neutropenic gram-negative sepsis. J Infect Dis. 1986 Oct;154(4):670–675. doi: 10.1093/infdis/154.4.670. [DOI] [PubMed] [Google Scholar]
  7. Chusid M. J., Davis S. D., Sarff L. D. Experimental Pseudomonas aeruginosa sepsis: absence of synergy between ticarcillin and tobramycin. J Lab Clin Med. 1983 Mar;101(3):441–449. [PubMed] [Google Scholar]
  8. Eilers R. J. Notification of final adoption of an international method and standard solution for hemoglobinometry specifications for preparation of standard solution. Am J Clin Pathol. 1967 Feb;47(2):212–214. doi: 10.1093/ajcp/47.2.212. [DOI] [PubMed] [Google Scholar]
  9. Gerber A. U., Vastola A. P., Brandel J., Craig W. A. Selection of aminoglycoside-resistant variants of Pseudomonas aeruginosa in an in vivo model. J Infect Dis. 1982 Nov;146(5):691–697. doi: 10.1093/infdis/146.5.691. [DOI] [PubMed] [Google Scholar]
  10. Greenwood D., Eley A. Comparative antipseudomonal activity of some newer beta-lactam agents. Antimicrob Agents Chemother. 1982 Feb;21(2):204–209. doi: 10.1128/aac.21.2.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hallander H. O., Dornbusch K., Gezelius L., Jacobson K., Karlsson I. Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method. Antimicrob Agents Chemother. 1982 Nov;22(5):743–752. doi: 10.1128/aac.22.5.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Issekutz A. C., Movat K. W., Movat H. Z. Enhanced vascular permeability and haemorrhage-inducing activity of zymosan-activated plasma. Clin Exp Immunol. 1980 Sep;41(3):505–511. [PMC free article] [PubMed] [Google Scholar]
  13. Johanson W. G., Jr, Pierce A. K., Sanford J. P., Thomas G. D. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med. 1972 Nov;77(5):701–706. doi: 10.7326/0003-4819-77-5-701. [DOI] [PubMed] [Google Scholar]
  14. Klastersky J., Cappel R., Daneau D. Clinical significance of in vitro synergism between antibiotics in gram-negative infections. Antimicrob Agents Chemother. 1972 Dec;2(6):470–475. doi: 10.1128/aac.2.6.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klastersky J., Meunier-Carpentier F., Prevost J. M. Significance of antimicrobial synergism for the outcome of gram negative sepsis. Am J Med Sci. 1977 Mar-Apr;273(2):157–167. doi: 10.1097/00000441-197703000-00005. [DOI] [PubMed] [Google Scholar]
  16. Neu H. C., Labthavikul P. Antibacterial activity and beta-lactamase stability of ceftazidime, an aminothiazolyl cephalosporin potentially active against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1982 Jan;21(1):11–18. doi: 10.1128/aac.21.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Norden C. W., Shaffer M. A. Activities of tobramycin and azlocillin alone and in combination against experimental osteomyelitis caused by Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1982 Jan;21(1):62–65. doi: 10.1128/aac.21.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Norden C. W., Wentzel H., Keleti E. Comparison of techniques for measurement of in vitro antibiotic synergism. J Infect Dis. 1979 Oct;140(4):629–633. doi: 10.1093/infdis/140.4.629. [DOI] [PubMed] [Google Scholar]
  19. Olson B., Weinstein R. A., Nathan C., Chamberlin W., Kabins S. A. Occult aminoglycoside resistance in Pseudomonas aeruginosa: epidemiology and implications for therapy and control. J Infect Dis. 1985 Oct;152(4):769–774. doi: 10.1093/infdis/152.4.769. [DOI] [PubMed] [Google Scholar]
  20. Pennington J. E., Ehrie M. G. Pathogenesis of Pseudomonas aeruginosa pneumonia during immunosuppression. J Infect Dis. 1978 Jun;137(6):764–774. doi: 10.1093/infdis/137.6.764. [DOI] [PubMed] [Google Scholar]
  21. Pennington J. E., Stone R. M. Comparison of antibiotic regimens for treatment of experimental pneumonia due to Pseudomonas. J Infect Dis. 1979 Dec;140(6):881–889. doi: 10.1093/infdis/140.6.881. [DOI] [PubMed] [Google Scholar]
  22. Pierce A. K., Sanford J. P. Aerobic gram-negative bacillary pneumonias. Am Rev Respir Dis. 1974 Nov;110(5):647–658. doi: 10.1164/arrd.1974.110.5.647. [DOI] [PubMed] [Google Scholar]
  23. Rehm S. R., Gross G. N., Pierce A. K. Early bacterial clearance from murine lungs. Species-dependent phagocyte response. J Clin Invest. 1980 Aug;66(2):194–199. doi: 10.1172/JCI109844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rusnak M. G., Drake T. A., Hackbarth C. J., Sande M. A. Single versus combination antibiotic therapy for pneumonia due to Pseudomonas aeruginosa in neutropenic guinea pigs. J Infect Dis. 1984 Jun;149(6):980–985. doi: 10.1093/infdis/149.6.980. [DOI] [PubMed] [Google Scholar]
  25. Scott R. E., Robson H. G. Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats. Antimicrob Agents Chemother. 1976 Oct;10(4):646–651. doi: 10.1128/aac.10.4.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Southern P. M., Jr, Mays B. B., Pierce A. K., Sanford J. P. Pulmonary clearance of Pseudomonas aeruginosa. J Lab Clin Med. 1970 Oct;76(4):548–559. [PubMed] [Google Scholar]

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

RESOURCES