Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis

Abstract : Moxifloxacinretains partial activity against some fluoroquinolone-resistant mutants of Mycobacterium tuberculosis . Levofloxacinis presumed to be as active as moxifloxacinagainst drug-susceptible tuberculosis and to have a better safety profile. : To compare the in vivo activity of levofloxacinand moxifloxacinagainst M. tuberculosis strains with various levels of fluoroquinolone resistance. BALB/c mice were intravenously infected with 10 6 M. tuberculosis H37Rv and three isogenic mutants: GyrA A90V, GyrB E540A and GyrB A543V. Treatment with 50 or 100 mg/kg levofloxacinand 60 or 66 mg/kg moxifloxacinwas given orally every 6 h, for 4 weeks. : Levofloxacin50 and 100 mg/kg q6h and moxifloxacin60 and 66 mg/kg q6h generated AUCs in mice equivalent to those of levofloxacin750 and 1000 mg/day and moxifloxacin400 and 800 mg/day, respectively, in humans. Moxifloxacin60 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), moxifloxacin60 mg/kg q6h did not prevent bacillary growth, whereas 66 mg/kg q6h had bacteriostatic activity. Levofloxacin50 mg/kg q6h had bactericidal activity against H37Rv (MIC ≤ 0.25 mg/L) but not against the mutant strains. Levofloxacin100 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). : All mutations reduced fluoroquinolone activity, even those classified as susceptible according to phenotypic tests. High-dose levofloxacinis less effective than high-dose moxifloxacinagainst both fluoroquinolone-resistant and -susceptible M. tuberculosis strains in mice.