Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis?

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Abstract

Background: Moxifloxacin retains partial activity against some fluoroquinolone-resistant mutants of Mycobacterium tuberculosis. Levofloxacin is presumed to be as active as moxifloxacin against drug-susceptible tuberculosis and to have a better safety profile. Objectives: To compare the in vivo activity of levofloxacin and moxifloxacin against M. tuberculosis strains with various levels of fluoroquinolone resistance. Methods: BALB/c mice were intravenously infected with 106 M. tuberculosis H37Rv and three isogenic mutants: GyrA A90V, GyrB E540A and GyrB A543V. Treatment with 50 or 100 mg/kg levofloxacin and 60 or 66 mg/kg moxifloxacin was given orally every 6 h, for 4 weeks. Results: Levofloxacin 50 and 100 mg/kg q6h and moxifloxacin 60 and 66 mg/kg q6h generated AUCs in mice equivalent to those of levofloxacin 750 and 1000mg/day and moxifloxacin 400 and 800 mg/day, respectively, in humans. Moxifloxacin 60 and 66 mg/kg q6h had bactericidal activity against strain H37Rv (MIC≥0.25 mg/L) and mutants GyrB E540A and GyrB A543V (MIC=0.5 mg/L). Against mutant GyrA A90V (MIC=2 mg/L), moxifloxacin 60 mg/kg q6h did not prevent bacillary growth, whereas 66 mg/kg q6h had bacteriostatic activity. Levofloxacin 50 mg/kg q6h had bactericidal activity against H37Rv (MIC≥0.25 mg/L) but not against the mutant strains. Levofloxacin 100 mg/kg q6h had bactericidal activity against H37Rv and mutants GyrB E540A (MIC"0.5 mg/L) and GyrB A543V (MIC=1 mg/L) but not against mutant GyrA A90V (MIC=4 mg/L). Conclusions: All mutations reduced fluoroquinolone activity, even those classified as susceptible according to phenotypic tests. High-dose levofloxacin is less effective than high-dose moxifloxacin against both fluoroquinolone-resistant and -susceptible M. tuberculosis strains in mice.

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APA

Maitre, T., Petitjean, G., Chauffour, A., Bernard, C., El Helali, N., Jarlier, V., … Veziris, N. (2017). Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis? Journal of Antimicrobial Chemotherapy, 72(8), 2326–2333. https://doi.org/10.1093/jac/dkx150

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