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. 1996 Nov;40(11):2483–2487. doi: 10.1128/aac.40.11.2483

Spectrum of activity of levofloxacin against nontuberculous mycobacteria and its activity against the Mycobacterium avium complex in combination with ethambutol, rifampin, roxithromycin, amikacin, and clofazimine.

N Rastogi 1, K S Goh 1, A Bryskier 1, A Devallois 1
PMCID: PMC163561  PMID: 8913450

Abstract

The spectrum of activity of levofloxacin was initially determined against 29 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs. Levofloxacin MICs were 1 to 2 dilutions lower compared with those obtained for ofloxacin and 8 to 64 dilutions lower compared with those obtained for its D-isomer. Levofloxacin MICs were below its peak level in serum (5.5 micrograms/ml following administration of a single oral dose of 350 mg) for 25 of 29 isolates tested. It possessed MICs below its peak level in serum for M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, M. chelonei, M. abcessus, M. fortuitum, and M. peregrinum. Regarding the M. avium complex, the MICs of levofloxacin for 11 clinical isolates (7 from human immunodeficiency virus-positive patients and 4 from human immunodeficiency virus-negative patients) were 1 to 2 dilutions lower than those of ofloxacin. Among 20 isolates belonging to 12 pathogenic mycobacterial species, the MBC/MIC ratios varied from 1 to 4 for levofloxacin and 2 to 4 for ofloxacin. When drug combinations were screened by using the radiometric x/y quotient methodology against five M. avium complex isolates, levofloxacin activity against all five isolates was enhanced by ethambutol and activity against three isolates was enhanced by clofazimine. Screening of three-drug combinations showed that the combination levofloxacin-ethambutol with a third potential anti-M. avium drug (rifampin, roxithromycin, amikacin, or clofazimine) resulted in enhanced activity for all 20 drug combinations screened.

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Selected References

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  1. Agins B. D., Berman D. S., Spicehandler D., el-Sadr W., Simberkoff M. S., Rahal J. J. Effect of combined therapy with ansamycin, clofazimine, ethambutol, and isoniazid for Mycobacterium avium infection in patients with AIDS. J Infect Dis. 1989 Apr;159(4):784–787. doi: 10.1093/infdis/159.4.784. [DOI] [PubMed] [Google Scholar]
  2. Baron E. J., Young L. S. Amikacin, ethambutol, and rifampin for treatment of disseminated Mycobacterium avium-intracellulare infections in patients with acquired immune deficiency syndrome. Diagn Microbiol Infect Dis. 1986 Sep;5(3):215–220. doi: 10.1016/0732-8893(86)90004-0. [DOI] [PubMed] [Google Scholar]
  3. Barrow W. W., Wright E. L., Goh K. S., Rastogi N. Activities of fluoroquinolone, macrolide, and aminoglycoside drugs combined with inhibitors of glycosylation and fatty acid and peptide biosynthesis against Mycobacterium avium. Antimicrob Agents Chemother. 1993 Apr;37(4):652–661. doi: 10.1128/aac.37.4.652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bazile S., Moreau N., Bouzard D., Essiz M. Relationships among antibacterial activity, inhibition of DNA gyrase, and intracellular accumulation of 11 fluoroquinolones. Antimicrob Agents Chemother. 1992 Dec;36(12):2622–2627. doi: 10.1128/aac.36.12.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bermudez L. E., Inderlied C. B., Kolonoski P., Wu M., Barbara-Burnham L., Young L. S. Activities of bay Y 3118, levofloxacin, and ofloxacin alone or in combination with ethambutol against Mycobacterium avium complex in vitro, in human macrophages, and in beige mice. Antimicrob Agents Chemother. 1996 Mar;40(3):546–551. doi: 10.1128/aac.40.3.546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Goodwin S. D., Gallis H. A., Chow A. T., Wong F. A., Flor S. C., Bartlett J. A. Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother. 1994 Apr;38(4):799–804. doi: 10.1128/aac.38.4.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Heifets L. B., Lindholm-Levy P. J. Bacteriostatic and bactericidal activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Tubercle. 1987 Dec;68(4):267–276. doi: 10.1016/0041-3879(87)90067-5. [DOI] [PubMed] [Google Scholar]
  10. Heifets L. B., Lindholm-Levy P. J., Comstock R. D. Clarithromycin minimal inhibitory and bactericidal concentrations against Mycobacterium avium. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856–858. doi: 10.1164/ajrccm/145.4_Pt_1.856. [DOI] [PubMed] [Google Scholar]
  11. Hoy J., Mijch A., Sandland M., Grayson L., Lucas R., Dwyer B. Quadruple-drug therapy for Mycobacterium avium-intracellulare bacteremia in AIDS patients. J Infect Dis. 1990 Apr;161(4):801–805. doi: 10.1093/infdis/161.4.801. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. JI B., Lounis N., Truffot-Pernot C., Grosset J. In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1995 Jun;39(6):1341–1344. doi: 10.1128/aac.39.6.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  17. Pascual A., Garcia I., Perea E. J. Fluorometric measurement of ofloxacin uptake by human polymorphonuclear leukocytes. Antimicrob Agents Chemother. 1989 May;33(5):653–656. doi: 10.1128/aac.33.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Rastogi N., Barrow W. W. Laboratory and clinical aspects of the Mycobacterium avium epidemic: contributing factors associated with variability of drug susceptibility and immune responsiveness, and the multifaceted nature of pathogenicity. Res Microbiol. 1994 Mar-Apr;145(3):167–168. doi: 10.1016/0923-2508(94)90012-4. [DOI] [PubMed] [Google Scholar]
  20. Rastogi N., Falkinham J. O., 3rd Solving the dilemma of antimycobacterial chemotherapy. Res Microbiol. 1996 Jan-Feb;147(1-2):7–10. doi: 10.1016/0923-2508(96)80196-3. [DOI] [PubMed] [Google Scholar]
  21. Rastogi N., Goh K. S., Bryskier A. Activities of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine against Mycobacterium avium complex. Antimicrob Agents Chemother. 1994 Jun;38(6):1433–1438. doi: 10.1128/aac.38.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rastogi N., Goh K. S., Bryskier A. In vitro activity of roxithromycin against 16 species of atypical mycobacteria and effect of pH on its radiometric MICs. Antimicrob Agents Chemother. 1993 Jul;37(7):1560–1562. doi: 10.1128/aac.37.7.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rastogi N., Labrousse V., Bryskier A. Intracellular activities of roxithromycin used alone and in association with other drugs against Mycobacterium avium complex in human macrophages. Antimicrob Agents Chemother. 1995 Apr;39(4):976–978. doi: 10.1128/aac.39.4.976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Rastogi N., Labrousse V., Goh K. S., De Sousa J. P. Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages. Antimicrob Agents Chemother. 1991 Dec;35(12):2473–2480. doi: 10.1128/aac.35.12.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saito H., Sato K., Tomioka H., Dekio S. In vitro antimycobacterial activity of a new quinolone, levofloxacin (DR-3355). Tuber Lung Dis. 1995 Oct;76(5):377–380. doi: 10.1016/0962-8479(95)90001-2. [DOI] [PubMed] [Google Scholar]
  27. Skinner P. S., Furney S. K., Kleinert D. A., Orme I. M. Comparison of activities of fluoroquinolones in murine macrophages infected with Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1995 Mar;39(3):750–753. doi: 10.1128/AAC.39.3.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Tulkens P. M. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):100–106. doi: 10.1007/BF01964420. [DOI] [PubMed] [Google Scholar]
  30. 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]

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