Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Jun;39(6):1341–1344. doi: 10.1128/aac.39.6.1341

In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis.

B JI 1, N Lounis 1, C Truffot-Pernot 1, J Grosset 1
PMCID: PMC162738  PMID: 7574527

Abstract

In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but the MICs at which 90% of the strains are inhibited were similar. The in vivo activity of LVFX against M. tuberculosis was compared with the activities of isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with 1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out six times weekly for 4 weeks. The severity of infection and effectiveness of treatment were assessed by survival rate, spleen weights, gross lung lesions, and enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti-M. tuberculosis activities of the treatments used ran in the following order: LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg) > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It seems, therefore, that the in vivo activity of LVFX is comparable to that produced by a twofold-greater dosage of OFLO. It is assumed that the maximal clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX displayed powerful bactericidal activity, promising effects against human tuberculosis may be achieved if patients are treated with the maximal clinically tolerated dosage of LVFX.

Full Text

The Full Text of this article is available as a PDF (234.5 KB).

Selected References

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

  1. Flor S. C., Rogge M. C., Chow A. T. Bioequivalence of oral and intravenous ofloxacin after multiple-dose administration to healthy male volunteers. Antimicrob Agents Chemother. 1993 Jul;37(7):1468–1472. doi: 10.1128/aac.37.7.1468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fu K. P., Lafredo S. C., Foleno B., Isaacson D. M., Barrett J. F., Tobia A. J., Rosenthale M. E. In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin. Antimicrob Agents Chemother. 1992 Apr;36(4):860–866. doi: 10.1128/aac.36.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Grosset J. H., Ji B. H., Guelpa-Lauras C. C., Perani E. G., N'Deli L. N. Clinical trial of pefloxacin and ofloxacin in the treatment of lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1990 Jun;58(2):281–295. [PubMed] [Google Scholar]
  4. 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]
  5. Hayakawa I., Atarashi S., Yokohama S., Imamura M., Sakano K., Furukawa M. Synthesis and antibacterial activities of optically active ofloxacin. Antimicrob Agents Chemother. 1986 Jan;29(1):163–164. doi: 10.1128/aac.29.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Imamura M., Shibamura S., Hayakawa I., Osada Y. Inhibition of DNA gyrase by optically active ofloxacin. Antimicrob Agents Chemother. 1987 Feb;31(2):325–327. doi: 10.1128/aac.31.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Israel D., Gillum J. G., Turik M., Harvey K., Ford J., Dalton H., Towle M., Echols R., Heller A. H., Polk R. Pharmacokinetics and serum bactericidal titers of ciprofloxacin and ofloxacin following multiple oral doses in healthy volunteers. Antimicrob Agents Chemother. 1993 Oct;37(10):2193–2199. doi: 10.1128/aac.37.10.2193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ji B., Perani E. G., Petinom C., N'Deli L., Grosset J. H. Clinical trial of ofloxacin alone and in combination with dapsone plus clofazimine for treatment of lepromatous leprosy. Antimicrob Agents Chemother. 1994 Apr;38(4):662–667. doi: 10.1128/aac.38.4.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Klemens S. P., Sharpe C. A., Rogge M. C., Cynamon M. H. Activity of levofloxacin in a murine model of tuberculosis. Antimicrob Agents Chemother. 1994 Jul;38(7):1476–1479. doi: 10.1128/aac.38.7.1476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lalande V., Truffot-Pernot C., Paccaly-Moulin A., Grosset J., Ji B. Powerful bactericidal activity of sparfloxacin (AT-4140) against Mycobacterium tuberculosis in mice. Antimicrob Agents Chemother. 1993 Mar;37(3):407–413. doi: 10.1128/aac.37.3.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mor N., Vanderkolk J., Heifets L. Inhibitory and bactericidal activities of levofloxacin against Mycobacterium tuberculosis in vitro and in human macrophages. Antimicrob Agents Chemother. 1994 May;38(5):1161–1164. doi: 10.1128/aac.38.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Neu H. C., Chin N. X. In vitro activity of S-ofloxacin. Antimicrob Agents Chemother. 1989 Jul;33(7):1105–1107. doi: 10.1128/aac.33.7.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pascual A., Garcia I., Perea E. J. Uptake and intracellular activity of an optically active ofloxacin isomer in human neutrophils and tissue culture cells. Antimicrob Agents Chemother. 1990 Feb;34(2):277–280. doi: 10.1128/aac.34.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sudre P., ten Dam G., Kochi A. Tuberculosis: a global overview of the situation today. Bull World Health Organ. 1992;70(2):149–159. [PMC free article] [PubMed] [Google Scholar]
  16. Tanaka M., Otsuki M., Une T., Nishino T. In-vitro and in-vivo activity of DR-3355, an optically active isomer of ofloxacin. J Antimicrob Chemother. 1990 Nov;26(5):659–666. doi: 10.1093/jac/26.5.659. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Une T., Fujimoto T., Sato K., Osada Y. In vitro activity of DR-3355, an optically active ofloxacin. Antimicrob Agents Chemother. 1988 Sep;32(9):1336–1340. doi: 10.1128/aac.32.9.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yew W. W., Piddock L. J., Li M. S., Lyon D., Chan C. Y., Cheng A. F. In-vitro activity of quinolones and macrolides against mycobacteria. J Antimicrob Chemother. 1994 Sep;34(3):343–351. doi: 10.1093/jac/34.3.343. [DOI] [PubMed] [Google Scholar]
  21. Yuk J. H., Nightingale C. H., Quintiliani R., Sweeney K. R. Bioavailability and pharmacokinetics of ofloxacin in healthy volunteers. Antimicrob Agents Chemother. 1991 Feb;35(2):384–386. doi: 10.1128/aac.35.2.384. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES