Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1974 Mar;5(3):281–288. doi: 10.1128/aac.5.3.281

Dissociation Between Results of In Vitro and In Vivo Antibiotic Susceptibility Tests for Some Strains of Pseudomonas aeruginosa

Starkey D Davis 1
PMCID: PMC428961  PMID: 4209069

Abstract

The relative efficacy in vivo of the polymyxin and aminoglycoside antibiotics in experimental Pseudomonas infection has apparently never been established. This study was designed to determine such efficacy in experimental infection of mice. Eleven strains of Pseudomonas aeruginosa were selected for the study, representing six of the seven recognized immunotypes. All strains were susceptible to colistin, gentamicin, and tobramycin in vitro, and all were virulent for mice. None was lethal because of preformed toxins. Infections were established in mice by intraperitoneal (i.p.) injection of 100 ID50 of bacteria (infectious doses that would kill 50% of the mice). Graduated doses of antibiotics or saline were given subcutaneously 1 h later. Infections by three strains of P. aeruginosa were cured by low doses of all three antibiotics. Infections by two strains were relatively resistant in vivo to all three antibiotics. Infections by seven strains were relatively resistant in vivo to colistimethate. For most strains, colistimethate was less effective in vivo than gentamicin or tobramycin. To determine the influence of the size of the bacterial inoculum upon the results of chemotherapy, groups of mice were infected with serial dilutions of bacterial suspensions and treated with antibiotics. The antibiotics were more effective when a lighter bacterial inoculum was used. However, colistimethate at 30 mg/kg failed to cure some infections established with an inoculum of only 10 ID50. To examine the possibility that death despite apparently adequate chemotherapy might be due to bacterial lysis and delayed release of toxins, numbers of viable bacteria in the peritoneal cavity of treated animals were determined by colony count. Antibiotic failure by colistimethate was associated with a steady rise in the number of i.p. bacteria. The findings support the conclusion that i.p. infections in mice with some strains of P. aeruginosa that are fully susceptible in vitro are relatively resistant to chemotherapy in vivo. The dissociation between in vitro and in vivo results was greatest for colistimethate.

Full text

PDF
281

Selected References

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

  1. Armstrong A. V., Stewart-Tull D. E., Roberts J. S. Characterisation of the Pseudomonas aeruginosa factor that inhibits mouse-liver mitochondrial respiration. J Med Microbiol. 1971 May;4(2):249–262. doi: 10.1099/00222615-4-2-249. [DOI] [PubMed] [Google Scholar]
  2. Atik M., Liu P. V., Hanson B. A., Amini S., Rosenberg C. F. Pseudomonas exotoxin shock. A preliminary report of studies in dogs. JAMA. 1968 Jul 15;205(3):134–140. doi: 10.1001/jama.205.3.134. [DOI] [PubMed] [Google Scholar]
  3. BERK R. S. PARTIAL PURIFICATION OF THE EXTRACELLULAR HEMOLYSIN OF PSEUDOMONAS AERUGINOSA. J Bacteriol. 1964 Sep;88:559–565. doi: 10.1128/jb.88.3.559-565.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bartell P. F., Orr T. E., Garcia M. The lethal events in experimental Pseudomonas aeruginosa infection of mice. J Infect Dis. 1968 Apr;118(2):165–172. doi: 10.1093/infdis/118.2.165. [DOI] [PubMed] [Google Scholar]
  5. Bauer A. W., Kirby W. M., Sherris J. C., Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed] [Google Scholar]
  6. Carney S. A., Jones R. J. Biological and immunochemical properties of culture filtrates of virulent and avirulent strains of Pseudomonas aeruginosa. Br J Exp Pathol. 1968 Oct;49(5):395–410. [PMC free article] [PubMed] [Google Scholar]
  7. Chen C. C., Feingold D. S. Locus of divalent cation inhibition of the bactericidal action of polymyxin B. Antimicrob Agents Chemother. 1972 Nov;2(5):331–335. doi: 10.1128/aac.2.5.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis S. D., Iannetta A. Antagonistic effect of calcium in serum on the activity of tobramycin against Pseudomonas. Antimicrob Agents Chemother. 1972 Jun;1(6):466–469. doi: 10.1128/aac.1.6.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis S. D., Iannetta A. Influence of serum and calcium on the bactericidal activity of gentamicin and carbenicillin on Pseudomonas aeruginosa. Appl Microbiol. 1972 Apr;23(4):775–779. doi: 10.1128/am.23.4.775-779.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis S. D., Iannetta A. Relative antagonism in vitro of calcium in serum to the bactericidal activities of gentamicin and tobramycin on Pseudomonas aeruginosa. Chemotherapy. 1973 Oct;19(4):243–253. doi: 10.1159/000221461. [DOI] [PubMed] [Google Scholar]
  11. Davis S. D., Iannetta A., Wedgwood R. J. Activity of colistin against Pseudomonas aeruginosa: inhibition by calcium. J Infect Dis. 1971 Dec;124(6):610–612. doi: 10.1093/infdis/124.6.610. [DOI] [PubMed] [Google Scholar]
  12. Davis S. D., Iannetta A., Wedgwood R. J. Antibiotics for Pseudomonas aeruginosa sepis: inadequate proof of efficacy. J Infect Dis. 1971 Jul;124(1):104–106. doi: 10.1093/infdis/124.1.104. [DOI] [PubMed] [Google Scholar]
  13. Davis S. D., Iannetta A., Wedgwood R. J. Paradoxical synergism and antagonism between serum and the antibacterial activity of colistin. J Infect Dis. 1971 Apr;123(4):392–398. doi: 10.1093/infdis/123.4.392. [DOI] [PubMed] [Google Scholar]
  14. Fisher M. W., Devlin H. B., Gnabasik F. J. New immunotype schema for Pseudomonas aeruginosa based on protective antigens. J Bacteriol. 1969 May;98(2):835–836. doi: 10.1128/jb.98.2.835-836.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fishman L. S., Armstrong D. Pseudomonas aeruginosa bacteremia in patients with neoplastic disease. Cancer. 1972 Sep;30(3):764–773. doi: 10.1002/1097-0142(197209)30:3<764::aid-cncr2820300326>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  16. Kobayashi F. Experimental infection with Pseudomonas aeruginosa in mice. I. The virulence of Pseudomonas aeruginosa for mice. Jpn J Microbiol. 1971 Jul;15(4):295–300. doi: 10.1111/j.1348-0421.1971.tb00584.x. [DOI] [PubMed] [Google Scholar]
  17. Kobayashi F. Experimental infection with Pseudomonas aeruginosa in mice. II. The fate of highly and low virulent strains in the peritoneal cavity and organs of mice. Jpn J Microbiol. 1971 Jul;15(4):301–307. [PubMed] [Google Scholar]
  18. Kubota Y., Liu P. V. An enterotoxin of Pseudomonas aeruginosa. J Infect Dis. 1971 Jan;123(1):97–98. doi: 10.1093/infdis/123.1.97. [DOI] [PubMed] [Google Scholar]
  19. Liu P. V. Exotoxins of Pseudomonas aeruginosa. I. Factors that influence the production of exotoxin A. J Infect Dis. 1973 Oct;128(4):506–513. doi: 10.1093/infdis/128.4.506. [DOI] [PubMed] [Google Scholar]
  20. Liu P. V. The roles of various fractions of Pseudomonas aeruginosa in its pathogenesis. II. Effects of lecithinase and protease. J Infect Dis. 1966 Feb;116(1):112–116. doi: 10.1093/infdis/116.1.112. [DOI] [PubMed] [Google Scholar]
  21. Liu P. V., Yoshii S., Hsieh H. Exotoxins of Pseudomonas aeruginosa. II. Concentration, purification, and characterization of exotoxin A. J Infect Dis. 1973 Oct;128(4):514–519. doi: 10.1093/infdis/128.4.514. [DOI] [PubMed] [Google Scholar]
  22. Meinke G., Barum J., Rosenberg B., Berk R. In Vivo Studies with the Partially Purified Protease (Elastase) from Pseudomonas aeruginosa. Infect Immun. 1970 Nov;2(5):583–589. doi: 10.1128/iai.2.5.583-589.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meinke G., Berk R. S. In vivo studies with a toxic fraction of Pseudomonas aeruginosa. Proc Soc Exp Biol Med. 1970 Nov;135(2):360–363. doi: 10.3181/00379727-135-35051. [DOI] [PubMed] [Google Scholar]
  24. NEWTON B. A. Reversal of the antibacterial activity of polymyxin by divalent cations. Nature. 1953 Jul 25;172(4369):160–161. [PubMed] [Google Scholar]
  25. NEWTON B. A. Site of action of polymyxin on Pseudomonas aeruginosa: antagonism by cations. J Gen Microbiol. 1954 Jun;10(3):491–499. doi: 10.1099/00221287-10-3-491. [DOI] [PubMed] [Google Scholar]
  26. Rugstad H. E. Characterization of a plasma kinin-inactivating enzyme produced by Pseudomonas aeruginosa. Br J Pharmacol Chemother. 1967 Jun;30(2):425–435. doi: 10.1111/j.1476-5381.1967.tb02149.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. SCHWARTZ B. S., WARREN M. R., BARKLEY F. A., LANDIS L. Microbiological and pharmacological studies of colistin sulfate and sodium colistinmethanesulfonate. Antibiot Annu. 1959;7:41–60. [PubMed] [Google Scholar]
  28. Schwarzmann S., Boring J. R. Antiphagocytic Effect of Slime from a Mucoid Strain of Pseudomonas aeruginosa. Infect Immun. 1971 Jun;3(6):762–767. doi: 10.1128/iai.3.6.762-767.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Waitz J. A., Moss E. L., Jr, Drube C. G., Weinstein M. J. Comparative activity of sisomicin, gentamicin, kanamycin, and tobramycin. Antimicrob Agents Chemother. 1972 Dec;2(6):431–437. doi: 10.1128/aac.2.6.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wick W. E., Welles J. S. Nebramycin, a new broad-spectrum antibiotic complex. IV. In vitro and in vivo laboratory evaluation. Antimicrob Agents Chemother (Bethesda) 1967;7:341–348. doi: 10.1128/AAC.7.3.341. [DOI] [PubMed] [Google Scholar]
  31. Young L. S., Armstrong D. Human immunity to Pseudomonas aeruginosa. I. In-vitro interaction of bacteria, polymorphonuclear leukocytes, and serum factors. J Infect Dis. 1972 Sep;126(3):257–276. doi: 10.1093/infdis/126.3.257. [DOI] [PubMed] [Google Scholar]
  32. Zimelis V. M., Jackson G. G. Activity of aminoglycoside antibiotics aganst Pseudomonas aeruginosa: specificity and site of calcium and magnesium antagonism. J Infect Dis. 1973 Jun;127(6):663–669. doi: 10.1093/infdis/127.6.663. [DOI] [PubMed] [Google Scholar]

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

RESOURCES