Bédos J P, Rieux V, Bauchet J, Muffat-Joly M, Carbon C, Azoulay-Dupuis E
Institut National de la Santé et de la Recherche Médicale, Unité 13, Hôpital Bichat-Claude Bernard, Paris, France.
Antimicrob Agents Chemother. 1998 Apr;42(4):862-7. doi: 10.1128/AAC.42.4.862.
The increasing emergence of penicillin-resistant and multidrug-resistant strains of Streptococcus pneumoniae will create a serious therapeutic problem in coming years. Trovafloxacin is a novel naphthyridone quinolone with promising activity against S. pneumoniae, including penicillin-resistant strains (MIC for 90% of the isolates tested, 0.25 microg/ml). We compared its in vivo efficacy with that of other fluoroquinolones (ciprofloxacin, temafloxacin, and sparfloxacin) and a reference beta-lactam (amoxicillin) in a model of acute experimental pneumonia. Immunocompetent Swiss mice were infected by peroral tracheal delivery of a virulent, penicillin-susceptible strain (MIC, 0.03 microg/ml); leukopenic Swiss mice were infected with three poorly virulent, penicillin-resistant strains (MICs, 4 to 8 microg/ml) and a ciprofloxacin-resistant strain (MIC, 32 microg/ml). Treatments were started 6 h (immunocompetent mice) or 3 h (leukopenic mice) after infection. Doses ranging from 12.5 to 300 mg/kg were given at 12- or 8-h intervals for 3 days. Trovafloxacin (25 mg/kg) was the most effective agent in vivo against penicillin-susceptible and -resistant strains. Corresponding survival rates were 2- to 4-fold higher than with 50-mg/kg sparfloxacin or temafloxacin and 8- to 16-fold higher than with 100-mg/kg ciprofloxacin. The ratios of the area under the concentration-time curve to the MIC in serum and lung tissue were more favorable with trovafloxacin than with the other quinolones. Efficacy in vivo correlated with pharmacokinetic parameters. Trovafloxacin shows potential for the treatment of infections due to penicillin-susceptible and -resistant S. pneumoniae but appears to be ineffective against a ciprofloxacin-resistant strain.
肺炎链球菌对青霉素耐药及多重耐药菌株的不断出现，将在未来几年引发严重的治疗难题。曲伐沙星是一种新型萘啶酮类喹诺酮，对肺炎链球菌包括耐青霉素菌株具有良好活性（90%受试分离株的 MIC 为 0.25μg/ml）。我们在急性实验性肺炎模型中，将其体内疗效与其他氟喹诺酮类药物（环丙沙星、替马沙星和司帕沙星）及一种对照β-内酰胺类药物（阿莫西林）进行了比较。免疫功能正常的瑞士小鼠经口气管接种一株对青霉素敏感的强毒株（MIC 为 0.03μg/ml）；白细胞减少的瑞士小鼠接种三株低毒力、耐青霉素菌株（MIC 为 4～8μg/ml）及一株耐环丙沙星菌株（MIC 为 32μg/ml）。感染后 6 小时（免疫功能正常小鼠）或 3 小时（白细胞减少小鼠）开始治疗。以 12 或 8 小时间隔给予 12.5～300mg/kg 的剂量，持续 3 天。曲伐沙星（25mg/kg）在体内对青霉素敏感及耐药菌株是最有效的药物。相应的存活率比 50mg/kg 的司帕沙星或替马沙星高 2～4 倍，比 100mg/kg 的环丙沙星高 8～16 倍。曲伐沙星在血清和肺组织中的浓度-时间曲线下面积与 MIC 的比值比其他喹诺酮类药物更有利。体内疗效与药代动力学参数相关。曲伐沙星显示出治疗由青霉素敏感及耐药肺炎链球菌引起感染的潜力，但对耐环丙沙星菌株似乎无效。
