Fink M P, Snydman D R, Niederman M S, Leeper K V, Johnson R H, Heard S O, Wunderink R G, Caldwell J W, Schentag J J, Siami G A
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Antimicrob Agents Chemother. 1994 Mar;38(3):547-57. doi: 10.1128/AAC.38.3.547.
Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.
将静脉注射环丙沙星与亚胺培南用于治疗重症肺炎进行了比较。在这项前瞻性、随机、双盲、多中心试验中（包括意向性分析），共纳入了405例重症肺炎患者。平均急性生理学与慢性健康状况评分系统（APACHE II）评分为17.6，79%的患者需要机械通气，78%的患者患有医院获得性肺炎。205例患者的亚组（98例接受环丙沙星治疗的患者和107例接受亚胺培南治疗的患者）可用于主要疗效终点评估。患者被随机分配接受静脉注射环丙沙星（每8小时400毫克）或亚胺培南（每8小时1000毫克）治疗，并根据肾功能调整剂量。主要和次要疗效终点是治疗结束后3至7天的细菌学和临床反应。接受环丙沙星治疗的患者细菌清除率高于接受亚胺培南治疗的患者（69%对59%；95%置信区间为-0.6%，26.2%；P = 0.069），临床反应率也显著更高（69%对56%；95%置信区间为3.5%，28.5%；P = 0.021）。环丙沙星和亚胺培南之间最大的差异在于对肠杆菌科细菌的清除（93%对65%；P = 0.009）。逐步逻辑回归分析表明以下因素与细菌清除相关：无铜绿假单胞菌（P < 0.01）、体重较高（P < 0.01）、APACHE II评分较低（P = 0.03）以及接受环丙沙星治疗（P = 0.04）。当初始呼吸道培养物中分离出铜绿假单胞菌时，两个治疗组在治疗期间均常见未能实现细菌清除和出现耐药性的情况（环丙沙星组分别为67%和33%，亚胺培南组分别为59%和53%）。观察到亚胺培南引起癫痫发作的频率高于环丙沙星（6%对1%；P = 0.028）。这些结果表明，在重症肺炎患者中，就细菌清除和临床反应而言，环丙沙星单药治疗至少与亚胺培南单药治疗相当。对于两个治疗组，铜绿假单胞菌的存在对治疗成功有负面影响。亚胺培南引起癫痫发作比环丙沙星更常见。重症肺炎的单药治疗是一种安全有效的初始策略，但如果怀疑或从患者中分离出铜绿假单胞菌，可能需要调整治疗方案。
