Kaatz G W, Seo S M, Barriere S L, Albrecht L M, Rybak M J
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan.
Antimicrob Agents Chemother. 1989 Aug;33(8):1184-7. doi: 10.1128/AAC.33.8.1184.
The therapeutic activities of ciprofloxacin (25 mg/kg every 8 h), rifampin (10 mg/kg every 24 h), ciprofloxacin plus rifampin, and vancomycin (17.5 mg/kg every 6 h) were compared by using the rabbit model of Staphylococcus aureus endocarditis. Animals infected with one of two test strains (SA1199 or SA487) were randomized into treatment groups and received 6 days of therapy. For SA1199, ciprofloxacin plus rifampin was most effective at reducing vegetation bacterial counts. For SA487, ciprofloxacin plus rifampin was as effective as vancomycin but less effective than ciprofloxacin alone. Resistance to ciprofloxacin at 5- and 10-fold the MIC emerged in the test strain in 82 and 55%, respectively, of rabbits infected with SA1199 and receiving ciprofloxacin monotherapy. The combination of ciprofloxacin and rifampin decreased these frequencies to 60% (P = 0.27) and 10% (P = 0.04). No resistance to ciprofloxacin was found in rabbits infected with SA487. We conclude that ciprofloxacin and ciprofloxacin plus rifampin are as efficacious as vancomycin in this model and that combining rifampin with ciprofloxacin may decrease the frequency at which high-level resistance to ciprofloxacin emerges. However, with respect to improved efficacy, the combination of ciprofloxacin and rifampin is unpredictable and may be detrimental.
采用金黄色葡萄球菌心内膜炎兔模型比较环丙沙星（每8小时25毫克/千克）、利福平（每24小时10毫克/千克）、环丙沙星加利福平以及万古霉素（每6小时17.5毫克/千克）的治疗活性。感染两种测试菌株之一（SA1199或SA487）的动物被随机分为治疗组并接受6天治疗。对于SA1199，环丙沙星加利福平在减少赘生物细菌数量方面最有效。对于SA487，环丙沙星加利福平与万古霉素效果相当，但不如单独使用环丙沙星有效。在感染SA1199并接受环丙沙星单药治疗的兔子中，测试菌株分别有82%和55%出现了5倍和10倍最低抑菌浓度（MIC）的环丙沙星耐药。环丙沙星和利福平联合使用使这些频率分别降至60%（P = 0.27）和10%（P = 0.04）。在感染SA487的兔子中未发现对环丙沙星的耐药。我们得出结论，在该模型中环丙沙星以及环丙沙星加利福平与万古霉素疗效相当，并且利福平与环丙沙星联合使用可能会降低环丙沙星高水平耐药出现的频率。然而，就提高疗效而言，环丙沙星和利福平联合使用效果不可预测，且可能有害。
