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JAC Advance Access published online on July 15, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg343
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Comparative antimicrobial activities of gatifloxacin, sitafloxacin and levofloxacin against Mycobacterium tuberculosis replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines

K. Sato 1 , H. Tomioka 1 *, C. Sano 1 , T. Shimizu 1 , K. Sano 2 , K. Ogasawara 2 , S. Cai 1 , and T. Kamei 3

1 Department of Microbiology and Immunology, Shimane Medical University, Izumo, Shimane 693-8501
2 Departments of Microbiology and Immunology, and Otorhinolaryngology, Shimane Medical University, Izumo, Shimane 693-8501
3 Shimane Institute of Health Science, Izumo, Shimane 693-0021, Japan

* Corresponding author. E-mail: tomioka{at}shimane-med.ac.jp.

Received 17 July 2002 ; revised 2 January 2003 ; accepted 29 May 2003

Abstract

Mycobacterium tuberculosis (MTB) is capable of invading not only macrophages (M{phi}s) but also type II pneumocytes. In this study, we compared the antimicrobial activities of fluoroquinolones, including gatifloxacin, sitafloxacin and levofloxacin, against the MTB replication in the Mono Mac 6 human M{phi} cell line (MM6-M{phi}s) and the A-549 human type II alveolar epithelial cell line (A-549 cells). When test quinolones were added at the MIC (0.125, 0.06 and 0.25 mg/L for gatifloxacin, sitafloxacin and levofloxacin, respectively) to the culture media of MTB-infected cells, these drugs exerted growth-inhibitory activity against intracellular organisms in the order of sitafloxacin > gatifloxacin > levofloxacin. On the other hand, when test quinolones were added at Cmax in the blood (1.7, 1.0 and 2.0 mg/L for gatifloxacin, sitafloxacin and levofloxacin, respectively), these drugs exhibited bactericidal activity against intracellular MTB in the order of gatifloxacin > sitafloxacin >= levofloxacin. In addition, when test drugs were added at 1/8Cmax to 1/2Cmax, the efficacy was in the order of sitafloxacin > gatifloxacin > levofloxacin. Thus, it appears that the MIC values of fluoroquinolones are not always predictive of their antimicrobial activity against intracellular MTB. In this context, it was also found that intracellular uptake of these quinolones by MM6-M{phi}s and A-549 cells was in the order of sitafloxacin > gatifloxacin > levofloxacin. This implies that the cellular permeability of these quinolones is an important factor that determines their efficacy to eliminate intracellular MTB organisms.

Keywords: gatifloxacin, sitafloxacin, macrophages, type II alveolar epithelial cells, Mycobacterium tuberculosis, fluoroquinolones, tuberculosis
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