Maitre Thomas, Petitjean Grégoire, Chauffour Aurélie, Bernard Christine, El Helali Najoua, Jarlier Vincent, Reibel Florence, Chavanet Pascal, Aubry Alexandra, Veziris Nicolas
Sorbonne Université, UPMC Univ. Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses, Team 13, INSERM U1135, Paris, France.
AP-HP, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène, Paris, France.
J Antimicrob Chemother. 2017 Aug 1;72(8):2326-2333. doi: 10.1093/jac/dkx150.
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.
To compare the in vivo activity of levofloxacin and moxifloxacin against 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 levofloxacin and 60 or 66 mg/kg moxifloxacin was given orally every 6 h, for 4 weeks.
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 1000 mg/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).
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.
莫西沙星对一些耐氟喹诺酮类的结核分枝杆菌突变株仍保留部分活性。左氧氟沙星被认为对药物敏感的结核病与莫西沙星活性相当，且安全性更好。
比较左氧氟沙星和莫西沙星对不同氟喹诺酮耐药水平的结核分枝杆菌菌株的体内活性。
将BALB/c小鼠静脉注射感染10⁶结核分枝杆菌H37Rv及三个同基因突变株：GyrA A90V、GyrB E540A和GyrB A543V。每6小时口服给予50或100mg/kg左氧氟沙星以及60或66mg/kg莫西沙星，持续4周。
左氧氟沙星50和100mg/kg q6h以及莫西沙星60和66mg/kg q6h在小鼠体内产生的药时曲线下面积（AUC）分别相当于人类左氧氟沙星750和1000mg/天以及莫西沙星400和800mg/天的AUC。莫西沙星60和66mg/kg q6h对菌株H37Rv（最低抑菌浓度[MIC]≤0.25mg/L）以及突变株GyrB E540A和GyrB A543V（MIC = 0.5mg/L）具有杀菌活性。对于突变株GyrA A90V（MIC = 2mg/L），莫西沙星60mg/kg q6h不能抑制细菌生长，而66mg/kg q6h具有抑菌活性。左氧氟沙星50mg/kg q6h对H37Rv（MIC≤0.25mg/L）具有杀菌活性，但对突变株无活性。左氧氟沙星100mg/kg q6h对H37Rv以及突变株GyrB E540A（MIC = 0.5mg/L）和GyrB A543V（MIC = 1mg/L）具有杀菌活性，但对突变株GyrA A90V（MIC = 4mg/L）无活性。
所有突变均降低了氟喹诺酮活性，即使是根据表型试验分类为敏感的突变。在小鼠中，高剂量左氧氟沙星对耐氟喹诺酮类和敏感的结核分枝杆菌菌株的疗效均低于高剂量莫西沙星。
