Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Mar;37(3):407–413. doi: 10.1128/aac.37.3.407

Powerful bactericidal activity of sparfloxacin (AT-4140) against Mycobacterium tuberculosis in mice.

V Lalande 1, C Truffot-Pernot 1, A Paccaly-Moulin 1, J Grosset 1, B Ji 1
PMCID: PMC187685  PMID: 8384811

Abstract

The bactericidal activities of various monotherapies and combined regimens were compared in mice at different stages after infection with Mycobacterium tuberculosis. These therapies mimicked the initial and continuation phases of chemotherapy for human tuberculosis. As monotherapy, the bactericidal activity of sparfloxacin (SPFX) was dose related; the activity of SPFX at 100 mg/kg of body weight was comparable to that of rifampin (RMP) and was significantly greater than those of isoniazid (INH), pyrazinamide (PZA), or ofloxacin (OFLO) during both the initial and continuation phases of chemotherapy. During the initial phase, the addition of SPFX did not enhance or diminish the activities of the combinations INH-RMP-PZA or RMP-PZA; the combinations SPFX-PZA-streptomycin (SM) and SPFX-PZA-kanamycin (KANA) displayed powerful bactericidal activity. Because the area under the plasma concentration-time curve of SPFX (100 mg/kg) in mice is similar to that of SPFX (400 mg) in humans, the promising bactericidal activity displayed by SPFX in mice might be achieved in humans by administration of the drug in a clinically tolerated dosage. In addition, the combinations SPFX-PZA-SM and SPFX-PZA-KANA may be useful for the treatment of multidrug-resistant tuberculosis.

Full text

PDF
407

Selected References

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

  1. Ben-Dov I., Mason G. R. Drug-resistant tuberculosis in a southern California hospital. Trends from 1969 to 1984. Am Rev Respir Dis. 1987 Jun;135(6):1307–1310. doi: 10.1164/arrd.1987.135.6.1307. [DOI] [PubMed] [Google Scholar]
  2. CANETTI G., FROMAN S., GROSSET J., HAUDUROY P., LANGEROVA M., MAHLER H. T., MEISSNER G., MITCHISON D. A., SULA L. MYCOBACTERIA: LABORATORY METHODS FOR TESTING DRUG SENSITIVITY AND RESISTANCE. Bull World Health Organ. 1963;29:565–578. [PMC free article] [PubMed] [Google Scholar]
  3. Canetti G., Fox W., Khomenko A., Mahler H. T., Menon N. K., Mitchison D. A., Rist N., Smelev N. A. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ. 1969;41(1):21–43. [PMC free article] [PubMed] [Google Scholar]
  4. Chu D. T., Fernandes P. B. Structure-activity relationships of the fluoroquinolones. Antimicrob Agents Chemother. 1989 Feb;33(2):131–135. doi: 10.1128/aac.33.2.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Culliton B. J. Drug-resistant TB may bring epidemic. Nature. 1992 Apr 9;356(6369):473–473. doi: 10.1038/356473a0. [DOI] [PubMed] [Google Scholar]
  6. Dickinson J. M., Mitchison D. A. Efficacy of intermittent pyrazinamide in experimental murine tuberculosis. Tubercle. 1991 Jun;72(2):110–114. doi: 10.1016/0041-3879(91)90037-s. [DOI] [PubMed] [Google Scholar]
  7. Ellard G. A. Absorption, metabolism and excretion of pyrazinamide in man. Tubercle. 1969 Jun;50(2):144–158. doi: 10.1016/0041-3879(69)90020-8. [DOI] [PubMed] [Google Scholar]
  8. Grosset J. H. Present status of chemotherapy for tuberculosis. Rev Infect Dis. 1989 Mar-Apr;11 (Suppl 2):S347–S352. doi: 10.1093/clinids/11.supplement_2.s347. [DOI] [PubMed] [Google Scholar]
  9. Grosset J., Truffot-Pernot C., Lacroix C., Ji B. Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice. Antimicrob Agents Chemother. 1992 Mar;36(3):548–551. doi: 10.1128/aac.36.3.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grosset J., Truffot C., Fermanian J., Lecoeur H. Activité stérilisante des différents antibiotiques dans la tuberculose expérimentale de la souris. Pathol Biol (Paris) 1982 Jun;30(6):444–448. [PubMed] [Google Scholar]
  11. Ji B., Truffot-Pernot C., Grosset J. In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis. Tubercle. 1991 Sep;72(3):181–186. doi: 10.1016/0041-3879(91)90004-c. [DOI] [PubMed] [Google Scholar]
  12. Nakamura S., Kurobe N., Ohue T., Hashimoto M., Shimizu M. Pharmacokinetics of a novel quinolone, AT-4140, in animals. Antimicrob Agents Chemother. 1990 Jan;34(1):89–93. doi: 10.1128/aac.34.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakamura S., Minami A., Nakata K., Kurobe N., Kouno K., Sakaguchi Y., Kashimoto S., Yoshida H., Kojima T., Ohue T. In vitro and in vivo antibacterial activities of AT-4140, a new broad-spectrum quinolone. Antimicrob Agents Chemother. 1989 Aug;33(8):1167–1173. doi: 10.1128/aac.33.8.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pretet S., Lebeaut A., Parrot R., Truffot C., Grosset J., Dinh-Xuan A. T. Combined chemotherapy including rifabutin for rifampicin and isoniazid resistant pulmonary tuberculosis. G.E.T.I.M. (Group for the Study and Treatment of Resistant Mycobacterial Infection). Eur Respir J. 1992 Jun;5(6):680–684. [PubMed] [Google Scholar]
  15. Truffot-Pernot C., Ji B., Grosset J. Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments. Tubercle. 1991 Mar;72(1):57–64. doi: 10.1016/0041-3879(91)90025-n. [DOI] [PubMed] [Google Scholar]
  16. Tsukamura M. Antituberculosis activity of ofloxacin (DL 8280) on experimental tuberculosis in mice. Am Rev Respir Dis. 1985 Oct;132(4):915–915. doi: 10.1164/arrd.1985.132.4.915. [DOI] [PubMed] [Google Scholar]
  17. Tsukamura M., Nakamura E., Yoshii S., Amano H. Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis. Am Rev Respir Dis. 1985 Mar;131(3):352–356. doi: 10.1164/arrd.1985.131.3.352. [DOI] [PubMed] [Google Scholar]

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

RESOURCES