Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1978 May;13(5):796–801. doi: 10.1128/aac.13.5.796

Relationship Between Gentamicin Susceptibility Criteria and Therapeutic Serum Levels for Pseudomonas aeruginosa in Mouse Infection Model

T I Nicas 1, L E Bryan 1
PMCID: PMC352333  PMID: 96735

Abstract

In this study estimations of in vivo and in vitro gentamicin susceptibility for a series of strains of Pseudomonas aeruginosa were compared. The series included an extremely susceptible strain, typically susceptible strains by current susceptibility criteria, and strains with enzymatic and permeability-mediated resistance. In vivo testing was done by using a mice protection test involving six 1-h doses of gentamicin and an inoculum of 50 50% lethal doses of P. aeruginosa. Both normal mice and cyclophosphamide-treated mice were used. It was found that peak serum levels and serum levels of gentamicin obtained just prior to the sixth dose (fifth dose trough levels) required for protection were much higher than minimal inhibitory concentrations (MICs) or minimal bactericidal concentrations (MBCs) obtained in high-cation medium. However, first dose trough levels were similar to MICs or MBCs. Only an extremely susceptible strain, 280, could be treated at antibiotic dosages and serum levels which are considered likely to be safe in humans. A distinct inoculum effect was found in the mice tests, with a 10-fold increase in inoculum producing a 4-fold increase in the amount of gentamicin required, but no inoculum effect was found for MICs. These results suggest that current susceptibility criteria in use for gentamicin and P. aeruginosa overestimate gentamicin susceptibility, particularly when low-cation growth medium is used for susceptibility testing and when treating disseminated infection.

Full text

PDF
796

Selected References

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

  1. Archer G., Fekety F. R., Jr Experimental endocarditis due to Pseudomonas aeruginosa. II. Therapy with carbenicillin and gentamicin. J Infect Dis. 1977 Sep;136(3):327–335. doi: 10.1093/infdis/136.3.327. [DOI] [PubMed] [Google Scholar]
  2. Bryan L. E., Haraphongse R., Van den Elzen H. M. Gentamicin resistance in clinical-isolates of Pseudomonas aeruginosa associated with diminished gentamicin accumulation and no detectable enzymatic modification. J Antibiot (Tokyo) 1976 Jul;29(7):743–753. doi: 10.7164/antibiotics.29.743. [DOI] [PubMed] [Google Scholar]
  3. Bryan L. E., Van Den Elzen H. M. Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrob Agents Chemother. 1977 Aug;12(2):163–177. doi: 10.1128/aac.12.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davis S. D. Activity of gentamicin, tobramycin, polymyxin B, and colistimethate in mouse protection tests with Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1975 Jul;8(1):50–53. doi: 10.1128/aac.8.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis S. D. Dissociation between results of in vitro and in vivo antibiotic susceptibility tests for some strains of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1974 Mar;5(3):281–288. doi: 10.1128/aac.5.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Flick M. R., Cluff L. E. Pseudomonas bacteremia. Review of 108 cases. Am J Med. 1976 Apr;60(4):501–508. doi: 10.1016/0002-9343(76)90716-6. [DOI] [PubMed] [Google Scholar]
  7. Garrod L. P., Waterworth P. M. Effect of medium composition on the apparent sensitivity of Pseudomonas aeruginosa to gentamicin. J Clin Pathol. 1969 Sep;22(5):534–538. doi: 10.1136/jcp.22.5.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gilbert D. N., Kutscher E., Ireland P., Barnett J. A., Sanford J. P. Effect of the concentrations of magnesium and calcium on the in-vitro susceptibility of Pseudomonas aeruginosa to gentamicin. J Infect Dis. 1971 Dec;124 (Suppl):S37–S45. doi: 10.1093/infdis/124.supplement_1.s37. [DOI] [PubMed] [Google Scholar]
  9. Goodman E. L., Van Gelder J., Holmes R., Hull A. R., Sanford J. P. Prospective comparative study of variable dosage and variable frequency regimens for administration of gentamicin. Antimicrob Agents Chemother. 1975 Oct;8(4):434–438. doi: 10.1128/aac.8.4.434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haas M. J., Davies J. Enzymatic acetylation as a means of determining serum aminoglycoside concentrations. Antimicrob Agents Chemother. 1973 Oct;4(4):497–499. doi: 10.1128/aac.4.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heifetz C. L., Chodubski J. A., Pearson I. A., Silverman C. A., Fisher M. W. Butirosin compared with gentamicin in vitro and in vivo. Antimicrob Agents Chemother. 1974 Aug;6(2):124–135. doi: 10.1128/aac.6.2.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jackson G. G., Riff L. J. Pseudomonas bacteremia: pharmacologic and other bases for failure of treatment with gentamicin. J Infect Dis. 1971 Dec;124 (Suppl):S185–S191. doi: 10.1093/infdis/124.supplement_1.s185. [DOI] [PubMed] [Google Scholar]
  13. Lumish R. M., Norden C. W. Therapy of neutropenic rats infected with Pseudomonas aeruginosa. J Infect Dis. 1976 May;133(5):538–547. doi: 10.1093/infdis/133.5.538. [DOI] [PubMed] [Google Scholar]
  14. McGowan J. E., Jr, Barnes M. W., Finland M. Bacteremia at Boston City Hospital: Occurrence and mortality during 12 selected years (1935-1972), with special reference to hospital-acquired cases. J Infect Dis. 1975 Sep;132(3):316–335. doi: 10.1093/infdis/132.3.316. [DOI] [PubMed] [Google Scholar]
  15. Pierson C. L., Johnson A. G., Feller I. Effect of cyclophosphamide on the immune response to Pseudomonas aeruginosa in mice. Infect Immun. 1976 Jul;14(1):168–177. doi: 10.1128/iai.14.1.168-177.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reller L. B., Schoenknecht F. D., Kenny M. A., Sherris J. C. Antibiotic susceptibility testing of Pseudomonas aeruginosa: selection of a control strain and criteria for magnesium and calcium content in media. J Infect Dis. 1974 Nov;130(5):454–463. doi: 10.1093/infdis/130.5.454. [DOI] [PubMed] [Google Scholar]
  17. Shahrabadi M. S., Bryan L. E., Van Den Elizen H. M. Further properties of P-2 R-factors of Pseudomonas aeruginosa and their relationship to other plasmid groups. Can J Microbiol. 1975 May;21(5):592–605. doi: 10.1139/m75-086. [DOI] [PubMed] [Google Scholar]
  18. Waitz J. A., Weinstein M. J. Recent microbiological studies with gentamicin. J Infect Dis. 1969 Apr-May;119(4):355–360. doi: 10.1093/infdis/119.4-5.355. [DOI] [PubMed] [Google Scholar]
  19. Weinstein M. J., Drube C. G., Moss E. L., Jr, Waitz J. A. Microbiologic studies related to bacterial resistance to gentamicin. J Infect Dis. 1971 Dec;124 (Suppl):S11–S17. doi: 10.1093/infdis/124.supplement_1.s11. [DOI] [PubMed] [Google Scholar]
  20. 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