Azoulay-Dupuis E, Vallee E, Veber B, Bedos J P, Bauchet J, Pocidalo J J
Institut National de la Santé et de la Recherche Médicale U.13, Hôpital Claude Bernard, Paris, France.
Antimicrob Agents Chemother. 1992 Dec;36(12):2698-703. doi: 10.1128/AAC.36.12.2698.
The increasing emergence of penicillin-resistant and multiresistant strains of Streptococcus pneumoniae may pose a problem in coming years. We therefore compared sparfloxacin, a new fluoroquinolone with improved potency against streptococci, with amoxicillin, the "gold standard" in this setting, and another fluoroquinolone, ciprofloxacin, in a mouse pneumonia model. Their efficacies against penicillin-susceptible (serotype 3), macrolide-resistant (serotype 1), penicillin-resistant (serotype 23), and multiresistant (serotype 6) S. pneumoniae strains were evaluated. Immunocompetent Swiss mice (serotypes 1 and 3) and leukopenic mice (serotypes 6 and 23) were infected by peroral tracheal delivery of 10(4) to 10(6) CFU. Subcutaneous injections of antibiotics were initiated at 6, 18, 48, or 72 h after infection (six injections at 12-h intervals). In the immunocompetent mice, 100% survival was obtained with sparfloxacin (50 mg/kg) and amoxicillin (5 mg/kg) against both penicillin-susceptible and macrolide-resistant strains; ciprofloxacin gave significantly lower survival rates. Two to four injections of sparfloxacin completely cleared bacteria from lungs and blood; the most rapid eradication was achieved with amoxicillin. Sparfloxacin also fully protected leukopenic mice against penicillin-resistant strains. The dose of amoxicillin (50 mg/kg) required to protect mice and eradicate penicillin-resistant and multiresistant strains was 10 times higher than that effective against penicillin-susceptible strains. The microbiological and pharmacokinetic properties of sparfloxacin (e.g., the time during which concentrations exceed the MIC of the test pathogen) accounted for its efficacy against susceptible and resistant strains of S. pneumoniae in this model.
肺炎链球菌对青霉素耐药及多重耐药菌株的不断出现，在未来几年可能会成为一个问题。因此，我们在小鼠肺炎模型中，将对链球菌效力有所提高的新型氟喹诺酮类药物司帕沙星，与该情况下的“金标准”阿莫西林以及另一种氟喹诺酮类药物环丙沙星进行了比较。评估了它们对青霉素敏感（3型血清型）、大环内酯类耐药（1型血清型）、青霉素耐药（23型血清型）和多重耐药（6型血清型）肺炎链球菌菌株的疗效。通过经口气管给予10⁴至10⁶CFU，对免疫功能正常的瑞士小鼠（1型和3型血清型）和白细胞减少的小鼠（6型和23型血清型）进行感染。在感染后6、18、48或72小时开始皮下注射抗生素（每隔12小时注射6次）。在免疫功能正常的小鼠中，司帕沙星（50mg/kg）和阿莫西林（5mg/kg）对青霉素敏感和大环内酯类耐药菌株均有100%的存活率；环丙沙星的存活率明显较低。注射2至4次司帕沙星可使肺部和血液中的细菌完全清除；阿莫西林清除细菌的速度最快。司帕沙星还能使白细胞减少的小鼠完全抵御青霉素耐药菌株。保护小鼠并根除青霉素耐药和多重耐药菌株所需的阿莫西林剂量（50mg/kg）比对青霉素敏感菌株有效的剂量高10倍。司帕沙星的微生物学和药代动力学特性（例如，浓度超过测试病原体MIC的时间）解释了其在该模型中对肺炎链球菌敏感和耐药菌株的疗效。
