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. 1971 Sep;22(3):329–333. doi: 10.1128/am.22.3.329-333.1971

In Vitro Chemotherapeutic Combinations Against Isoniazid-Resistant Mycobacterium tuberculosis and Mycobacterium fortuitum

Elliot Goldstein 1,2,3,1, M Carroll Eagle 1,2,3, M L LaCasse 1,2,3
PMCID: PMC376309  PMID: 4330314

Abstract

It is an acceptable medical practice to use second-line antimycobacterial drugs in combination with isoniazid in treatment of isoniazid-resistant tuberculosis. Recent investigations have demonstrated the importance of determining chemotherapeutic interaction in instances of multiple antibiotic use. We studied the inhibitory effect of combinations of isoniazid with ethambutol, rifampin, ethionamide, cycloserine, viomycin, and kanamycin against three isoniazid-resistant strains of Mycobacterium tuberculosis and three strains of M. fortuitum. The isobologram technique with drug concentrations of 0.4 to 100 μg/ml was used. With the exception of single instances in which kanamycin plus isoniazid (M. tuberculosis strain 9999) and ethionamide plus isoniazid (M. fortuitum strain 2080) seemed to have a synergistic effect, neither synergy nor antagonism was noted for any of the combinations. These studies show that the combined use of isoniazid and a second line antimycobacterial agent results in vitro in indifferent inhibitory activity.

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Selected References

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

  1. BENSON W. M., STEFKO P. L., ROE M. D. Pharmacologic and toxicologic observations on hydrazine derivatives of isonicotinic acid (rimifon, marsilid). Am Rev Tuberc. 1952 Apr;65(4):376–391. doi: 10.1164/art.1952.65.4.376. [DOI] [PubMed] [Google Scholar]
  2. BERNSTEIN J., LOTT W. A., STEINBERG B. A., YALE H. L. Chemotherapy of experimental tuberculosis. V. Isonicotinic acid hydrazide (nydrazid) and related compounds. Am Rev Tuberc. 1952 Apr;65(4):357–364. doi: 10.1164/art.1952.65.4.357. [DOI] [PubMed] [Google Scholar]
  3. Davies J., Gorini L., Davis B. D. Misreading of RNA codewords induced by aminoglycoside antibiotics. Mol Pharmacol. 1965 Jul;1(1):93–106. [PubMed] [Google Scholar]
  4. Eickhoff T. C., Bennett J. V., Hayes P. S., Feeley J. Pseudomonas pseudomallei: susceptibility to chemotherapeutic agents. J Infect Dis. 1970 Feb;121(2):95–102. doi: 10.1093/infdis/121.2.95. [DOI] [PubMed] [Google Scholar]
  5. Eickhoff T. C. In vitro effects of carbenicillin combined with gentamicin or polymyxin B against Pseudomonas aeruginosa. Appl Microbiol. 1969 Sep;18(3):469–473. doi: 10.1128/am.18.3.469-473.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FORBES M., KUCK N. A., PEETS E. A. Mode of action of ethambutol. J Bacteriol. 1962 Nov;84:1099–1103. doi: 10.1128/jb.84.5.1099-1103.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Forbes M., Peets E. A., Kuck N. A. Effect of ethambutol on Mycobacteria. Ann N Y Acad Sci. 1966 Apr 20;135(2):726–731. doi: 10.1111/j.1749-6632.1966.tb45518.x. [DOI] [PubMed] [Google Scholar]
  8. GANGADHARAM P. R., HAROLD F. M., SCHAEFER W. B. Selective inhibition of nucleic acid synthesis in Mycobacterium tuberculosis by isoniazid. Nature. 1963 May 18;198:712–714. doi: 10.1038/198712b0. [DOI] [PubMed] [Google Scholar]
  9. HOEPRICH P. D. ALANINE: CYCLOSERINE ANTAGONISM. III. QUANTITATIVE ASPECTS AND RELATION TO HEATING OF CULTURE MEDIA. J Lab Clin Med. 1963 Oct;62:657–662. [PubMed] [Google Scholar]
  10. Hawkins J. E., McClean V. R. Comparative studies of cycloserine inhibition of mycobacteria. Am Rev Respir Dis. 1966 Apr;93(4):594–602. doi: 10.1164/arrd.1966.93.4.594. [DOI] [PubMed] [Google Scholar]
  11. Jawetz E. The use of combinations of antimicrobial drugs. Annu Rev Pharmacol. 1968;8:151–170. doi: 10.1146/annurev.pa.08.040168.001055. [DOI] [PubMed] [Google Scholar]
  12. KUCK N. A., PEETS E. A., FORBES M. Mode of action of ethambutol on Mycobacterium tuberculosis, strain H37R V. Am Rev Respir Dis. 1963 Jun;87:905–906. doi: 10.1164/arrd.1963.87.6.905. [DOI] [PubMed] [Google Scholar]
  13. Lorian V., Finland M. In vitro effect of rifampin on mycobacteria. Appl Microbiol. 1969 Feb;17(2):202–207. doi: 10.1128/am.17.2.202-207.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. MCCUNE R. M., Jr, MCDERMOTT W., TOMPSETT R. The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug. J Exp Med. 1956 Nov 1;104(5):763–802. doi: 10.1084/jem.104.5.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MCCUNE R. M., Jr, TOMPSETT R. Fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. I. The persistence of drug-susceptible tubercle bacilli in the tissues despite prolonged antimicrobial therapy. J Exp Med. 1956 Nov 1;104(5):737–762. doi: 10.1084/jem.104.5.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McDermott W. The story of INH. J Infect Dis. 1969 Jun;119(6):678–683. doi: 10.1093/infdis/119.6.678. [DOI] [PubMed] [Google Scholar]
  17. Mitchell R. S. Control of tuberculosis. N Engl J Med. 1967 Apr 20;276(16):905–contd. doi: 10.1056/NEJM196704202761606. [DOI] [PubMed] [Google Scholar]
  18. SCHAEFER W. B. The effect of isoniazid on growing and resting tubercle bacilli. Am Rev Tuberc. 1954 Jan;69(1):125–127. doi: 10.1164/art.1954.69.1.125. [DOI] [PubMed] [Google Scholar]
  19. Sabath L. D. Synergy of antibacterial substances by apparently known mechanisms. Antimicrob Agents Chemother (Bethesda) 1967;7:210–217. [PubMed] [Google Scholar]
  20. WEINBERG E. D. The mutual effects of antimicrobial compounds and metallic cations. Bacteriol Rev. 1957 Mar;21(1):46–68. doi: 10.1128/br.21.1.46-68.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wehrli W., Nüesch J., Knüsel F., Staehelin M. Action of rifamycins on RNA polymerase. Biochim Biophys Acta. 1968 Mar 18;157(1):215–217. doi: 10.1016/0005-2787(68)90285-2. [DOI] [PubMed] [Google Scholar]
  22. Youatt J. A review of the action of isoniazid. Am Rev Respir Dis. 1969 May;99(5):729–749. doi: 10.1164/arrd.1969.99.5.729. [DOI] [PubMed] [Google Scholar]

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