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. 1995 Jun;39(6):1349–1354. doi: 10.1128/aac.39.6.1349

Activities of poloxamer CRL8131 against Mycobacterium tuberculosis in vitro and in vivo.

C Jagannath 1, H S Allaudeen 1, R L Hunter 1
PMCID: PMC162740  PMID: 7574529

Abstract

A poloxamer surfactant, CRL8131, was evaluated for activity against Mycobacterium tuberculosis (Erdman) by itself and in combination with antibiotics in broth culture, in a macrophage cell line assay, and in testing with mice. In the broth culture, CRL8131 suppressed the growth of M. tuberculosis and produced synergistic effects in combination with isoniazid, rifampin, and streptomycin. It also displayed synergy with isoniazid and rifampin against two drug-resistant isolates. In the macrophage cell line assay, CRL8131 produced a synergistic effect on intracellular killing of M. tuberculosis by isoniazid, rifampin, streptomycin, pyrazinamide, thiacetazone, D-cycloserine, ethionamide, amikacin, clindamycin, and p-aminosalicylic acid. It demonstrated no synergy or antagonism with ethambutol, gentamicin, kanamycin, ciprofloxacin, or nalidixic acid. Finally, with C57BL/6 mice infected with M. tuberculosis, a combination of CRL8131 and either thiacetazone or pyrazinamide produced 100% survival at 40 days whereas the antibiotics produced only 33% survival and CRL8131 produced 0% survival when used as single agents. This improved survival rate was associated with a significant reduction in the number of organisms in the lungs and spleens of infected mice.

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Selected References

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  1. Bass J. B., Jr, Farer L. S., Hopewell P. C., O'Brien R., Jacobs R. F., Ruben F., Snider D. E., Jr, Thornton G. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J Respir Crit Care Med. 1994 May;149(5):1359–1374. doi: 10.1164/ajrccm.149.5.8173779. [DOI] [PubMed] [Google Scholar]
  2. Berenbaum M. C. A method for testing for synergy with any number of agents. J Infect Dis. 1978 Feb;137(2):122–130. doi: 10.1093/infdis/137.2.122. [DOI] [PubMed] [Google Scholar]
  3. CORNFORTH J. W., HART P. D., NICHOLLS G. A., REES R. J., STOCK J. A. Antituberculous effects of certain surface-active polyoxyethylene ethers. Br J Pharmacol Chemother. 1955 Mar;10(1):73–88. doi: 10.1111/j.1476-5381.1955.tb00063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CORNFORTH J. W., HART P. D., REES R. J. W., STOCK J. A. Antituberculous effect of certain surface-active polyoxyethylene ethers in mice. Nature. 1951 Jul 28;168(4265):150–153. doi: 10.1038/168150a0. [DOI] [PubMed] [Google Scholar]
  5. Comai K., Sullivan A. C. Antiobesity activity of pluronic L-101. Int J Obes. 1980;4(1):33–42. [PubMed] [Google Scholar]
  6. Crowle A. J., Tsang A. Y., Vatter A. E., May M. H. Comparison of 15 laboratory and patient-derived strains of Mycobacterium avium for ability to infect and multiply in cultured human macrophages. J Clin Microbiol. 1986 Nov;24(5):812–821. doi: 10.1128/jcm.24.5.812-821.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hart P. D. Mycobacterium tuberculosis in macrophages: effect of certain surfactants and other membrane-active compounds. Science. 1968 Nov 8;162(3854):686–689. doi: 10.1126/science.162.3854.686. [DOI] [PubMed] [Google Scholar]
  8. Hart P. D., Payne S. N. Effects of non-ionic surfactants that modify experimental tuberculosis on lipase activity of macrophages. Br J Pharmacol. 1971 Sep;43(1):190–196. doi: 10.1111/j.1476-5381.1971.tb07168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoffner S. E., Källenius G., Beezer A. E., Svenson S. B. Studies on the mechanisms of the synergistic effects of ethambutol and other antibacterial drugs on Mycobacterium avium complex. Acta Leprol. 1989;7 (Suppl 1):195–199. [PubMed] [Google Scholar]
  10. Howerton D. A., Hunter R. L., Ziegler H. K., Check I. J. Induction of macrophage Ia expression in vivo by a synthetic block copolymer, L81. J Immunol. 1990 Mar 1;144(5):1578–1584. [PubMed] [Google Scholar]
  11. Hunter R., Olsen M., Buynitzky S. Adjuvant activity of non-ionic block copolymers. IV. Effect of molecular weight and formulation on titre and isotype of antibody. Vaccine. 1991 Apr;9(4):250–256. doi: 10.1016/0264-410x(91)90108-i. [DOI] [PubMed] [Google Scholar]
  12. Hunter R., Strickland F., Kézdy F. The adjuvant activity of nonionic block polymer surfactants. I. The role of hydrophile-lipophile balance. J Immunol. 1981 Sep;127(3):1244–1250. [PubMed] [Google Scholar]
  13. Jagannath C., Reddy V. M., Gangadharam P. R. Enhancement of drug susceptibility of multi-drug resistant strains of Mycobacterium tuberculosis by ethambutol and dimethyl sulphoxide. J Antimicrob Chemother. 1995 Mar;35(3):381–390. doi: 10.1093/jac/35.3.381. [DOI] [PubMed] [Google Scholar]
  14. Kondo E., Kanai K. Triton WR-1339 as a biological-response modifier in mycobacterial infection. Jpn J Med Sci Biol. 1986 Apr;39(2):35–47. doi: 10.7883/yoken1952.39.35. [DOI] [PubMed] [Google Scholar]
  15. LOVELOCK J. E., REES R. J. Possible site and mode of action of certain lipotropic macromolecules in tuberculosis. Nature. 1955 Jan 22;175(4447):161–163. doi: 10.1038/175161a0. [DOI] [PubMed] [Google Scholar]
  16. Rastogi N., Blom-Potar M. C. Intracellular bactericidal activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis H37Rv multiplying in the J-774 macrophage cell line. Zentralbl Bakteriol. 1990 Jun;273(2):195–199. doi: 10.1016/s0934-8840(11)80249-5. [DOI] [PubMed] [Google Scholar]
  17. Rastogi N., Labrousse V. Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex. Antimicrob Agents Chemother. 1991 Mar;35(3):462–470. doi: 10.1128/aac.35.3.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schmolka I. R. Artificial blood emulsifiers. Fed Proc. 1975 May;34(6):1449–1453. [PubMed] [Google Scholar]
  19. Vaara M. Agents that increase the permeability of the outer membrane. Microbiol Rev. 1992 Sep;56(3):395–411. doi: 10.1128/mr.56.3.395-411.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wall T. C., Califf R. M., Blankenship J., Talley J. D., Tannenbaum M., Schwaiger M., Gacioch G., Cohen M. D., Sanz M., Leimberger J. D. Intravenous Fluosol in the treatment of acute myocardial infarction. Results of the Thrombolysis and Angioplasty in Myocardial Infarction 9 Trial. TAMI 9 Research Group. Circulation. 1994 Jul;90(1):114–120. doi: 10.1161/01.cir.90.1.114. [DOI] [PubMed] [Google Scholar]

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