Abstract
In this study the compounds levofloxacin and sparfloxacin, as well as three experimental compounds (AMQ2, AMQ4, and AMQ5), were compared with isoniazid and rifabutin in terms of their capacity to inhibit the intracellular growth of the drug-susceptible Mycobacterium tuberculosis strain Erdman and the isoniazid-resistant katG gene-negative strain 24 within monolayers of mouse bone marrow-derived macrophages. Both levofloxacin and sparfloxacin, as well as compound AMQ4, had substantial activity in this physiologically relevant model, further confirming the potential usefulness of this class of compounds in the therapy of tuberculosis.
Full Text
The Full Text of this article is available as a PDF (187.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bloom B. R., Murray C. J. Tuberculosis: commentary on a reemergent killer. Science. 1992 Aug 21;257(5073):1055–1064. doi: 10.1126/science.257.5073.1055. [DOI] [PubMed] [Google Scholar]
- 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]
- Ellner J. J., Hinman A. R., Dooley S. W., Fischl M. A., Sepkowitz K. A., Goldberger M. J., Shinnick T. M., Iseman M. D., Jacobs W. R., Jr Tuberculosis symposium: emerging problems and promise. J Infect Dis. 1993 Sep;168(3):537–551. doi: 10.1093/infdis/168.3.537. [DOI] [PubMed] [Google Scholar]
- Franzblau S. G., Parrilla M. L., Chan G. P. Sparfloxacin is more bactericidal than ofloxacin against Mycobacterium leprae in mice. Int J Lepr Other Mycobact Dis. 1993 Mar;61(1):66–69. [PubMed] [Google Scholar]
- 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]
- Gerding D. N., Hitt J. A. Tissue penetration of the new quinolones in humans. Rev Infect Dis. 1989 Jul-Aug;11 (Suppl 5):S1046–S1057. doi: 10.1093/clinids/11.supplement_5.s1046. [DOI] [PubMed] [Google Scholar]
- 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]
- Iseman M. D. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993 Sep 9;329(11):784–791. doi: 10.1056/NEJM199309093291108. [DOI] [PubMed] [Google Scholar]
- 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]
- Klopman G., Li J. Y., Wang S., Pearson A. J., Chang K., Jacobs M. R., Bajaksouzian S., Ellner J. J. In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations. Antimicrob Agents Chemother. 1994 Aug;38(8):1794–1802. doi: 10.1128/aac.38.8.1794. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klopman G., Wang S., Jacobs M. R., Bajaksouzian S., Edmonds K., Ellner J. J. Anti-Mycobacterium avium activity of quinolones: in vitro activities. Antimicrob Agents Chemother. 1993 Sep;37(9):1799–1806. doi: 10.1128/aac.37.9.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Leysen D. C., Haemers A., Pattyn S. R. Mycobacteria and the new quinolones. Antimicrob Agents Chemother. 1989 Jan;33(1):1–5. doi: 10.1128/aac.33.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lockley M. R., Wise R., Dent J. The pharmacokinetics and tissue penetration of ofloxacin. J Antimicrob Chemother. 1984 Dec;14(6):647–652. doi: 10.1093/jac/14.6.647. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Ordway D. J., Sonnenberg M. G., Donahue S. A., Belisle J. T., Orme I. M. Drug-resistant strains of Mycobacterium tuberculosis exhibit a range of virulence for mice. Infect Immun. 1995 Feb;63(2):741–743. doi: 10.1128/iai.63.2.741-743.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Rastogi N., Goh K. S. In vitro activity of the new difluorinated quinolone sparfloxacin (AT-4140) against Mycobacterium tuberculosis compared with activities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1991 Sep;35(9):1933–1936. doi: 10.1128/aac.35.9.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Skinner P. S., Furney S. K., Jacobs M. R., Klopman G., Ellner J. J., Orme I. M. A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions. Antimicrob Agents Chemother. 1994 Nov;38(11):2557–2563. doi: 10.1128/aac.38.11.2557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Van der Auwera P., Matsumoto T., Husson M. Intraphagocytic penetration of antibiotics. J Antimicrob Chemother. 1988 Aug;22(2):185–192. doi: 10.1093/jac/22.2.185. [DOI] [PubMed] [Google Scholar]
- Young L. S., Berlin O. G., Inderlied C. B. Activity of ciprofloxacin and other fluorinated quinolones against mycobacteria. Am J Med. 1987 Apr 27;82(4A):23–26. [PubMed] [Google Scholar]
- Zhang Y., Heym B., Allen B., Young D., Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature. 1992 Aug 13;358(6387):591–593. doi: 10.1038/358591a0. [DOI] [PubMed] [Google Scholar]