Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Jun;34(6):1035–1040. doi: 10.1128/aac.34.6.1035

Quantification of antibiotic drug potency by a two-compartment radioassay of bacterial growth.

V Boonkitticharoen 1, J C Ehrhardt 1, P T Kirchner 1
PMCID: PMC171753  PMID: 2144102

Abstract

The two-compartment radioassay for microbial kinetics based on continuous measurement of the 14CO2 released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial 14CO2 liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and tetracycline. The implications of dose-response curves are discussed on the basis of the receptor site concept for drug action. The assay sensitivities for chloramphenicol and tetracycline were similar to those obtained by the cell counting method, but the sensitivity of the radioassay was at least 10 times greater for spectinomycin.

Full text

PDF
1035

Selected References

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

  1. BROWN M. R., GARRETT E. R. KINETICS AND MECHANISMS OF ACTION OF ANTIBIOTICS ON MICROORGANISMS. I. REPRODUCIBILITY OF ESCHERICHIA COLI GROWTH CURVES AND DEPENDENCE UPON TETRACYCLINE CONCENTRATION. J Pharm Sci. 1964 Feb;53:179–183. doi: 10.1002/jps.2600530215. [DOI] [PubMed] [Google Scholar]
  2. Boonkitticharoen V., Ehrhardt J. C., Kirchner P. T. Bacterial growth kinetics: modelling and evaluation of two-compartment radioassay. Can J Microbiol. 1989 Sep;35(9):874–880. doi: 10.1139/m89-146. [DOI] [PubMed] [Google Scholar]
  3. Boonkitticharoen V., Ehrhardt J. C., Kirchner P. T. Radiometric assay of bacterial growth: analysis of factors determining system performance and optimization of assay technique. J Nucl Med. 1987 Feb;28(2):209–217. [PubMed] [Google Scholar]
  4. Buddemeyer E. U. Liquid scintillation vial for cumulative and continuous radiometric measurement of in vitro metabolism. Appl Microbiol. 1974 Aug;28(2):177–180. doi: 10.1128/am.28.2.177-180.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buddemeyer E. U., Wells G. M., Hutchinson R., Cooper M. D., Johnston G. S. Radiometric estimation of the replication time of bacteria in culture: an objective and precise approach to quantitative microbiology. J Nucl Med. 1978 Jun;19(6):619–625. [PubMed] [Google Scholar]
  6. D'Antonio R. G., Camargo E. E., Gedra T., Wagner H. N., Jr, Charache P. Rapid radiometric serum test for antibiotic activity. Antimicrob Agents Chemother. 1982 Feb;21(2):236–240. doi: 10.1128/aac.21.2.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeBlanc H. J., Jr, Charache P., Wagner H. N., Jr Automatic radiometric measurement of antibiotic effect on bacterial growth. Antimicrob Agents Chemother. 1972 Nov;2(5):360–366. doi: 10.1128/aac.2.5.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DeLand F. H. Metabolic inhibition as an index of bacterial susceptibility to drugs. Antimicrob Agents Chemother. 1972 Nov;2(5):405–412. doi: 10.1128/aac.2.5.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Franzblau S. G. Oxidation of palmitic acid by Mycobacterium leprae in an axenic medium. J Clin Microbiol. 1988 Jan;26(1):18–21. doi: 10.1128/jcm.26.1.18-21.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harvey R. J., Koch A. L. How partially inhibitory concentrations of chloramphenicol affect the growth of Escherichia coli. Antimicrob Agents Chemother. 1980 Aug;18(2):323–337. doi: 10.1128/aac.18.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heman-Ackah S. M. Comparison of tetracycline action on Staphylococcus aureus and Escherichia coli by microbial kinetics. Antimicrob Agents Chemother. 1976 Aug;10(2):223–228. doi: 10.1128/aac.10.2.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mielck J. B., Garrett E. R. Kinetics and mechanisms of drug action on microorganisms. X. Action of spectinomycin on Escherichia coli by microbial kinetics. J Pharm Sci. 1970 Jun;59(6):760–765. doi: 10.1002/jps.2600590607. [DOI] [PubMed] [Google Scholar]
  13. Reinicke B., Blümel P., Giesbrecht P. Reduced degradability by lysozyme of staphylococcal cell walls after chloramphenicol treatment. Arch Microbiol. 1983 Aug;135(2):120–124. doi: 10.1007/BF00408020. [DOI] [PubMed] [Google Scholar]
  14. Siddiqi S. H., Libonati J. P., Middlebrook G. Evaluation of rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 1981 May;13(5):908–912. doi: 10.1128/jcm.13.5.908-912.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Yangco B. G., Eikman E. A., Solomon D. A., Deresinski S. C., Madden J. A. Rapid radiometric method for determining drug susceptibility of Mycobacterium avium-intracellulare. Antimicrob Agents Chemother. 1981 Apr;19(4):534–539. doi: 10.1128/aac.19.4.534. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES