Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia
Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia
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DOI：
10.1086/533441
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发表时间：
2008-04-15
影响因子：
11.8
通讯作者：
Alder, Jeff
中科院分区：
文献类型：
--
作者：
Pertel, Peter E.;Bernardo, Patricia;Alder, Jeff
Objective.我们试图比较达托霉素和头孢曲松治疗社区获得性肺炎（CAP）患者的疗效。进行了两项III期随机、双盲试验，纳入了因CAP住院的成人患者。患者接受静脉注射达托霉素（4 mg/kg）或头孢曲松（2 g），每日一次，持续5-14天。革兰阴性菌感染患者可加用氨曲南。在意向治疗人群和临床可评估人群中，治愈检验访视时的临床应答是主要疗效终点。合并试验数据后，意向治疗人群包括413例达托霉素治疗患者和421例头孢曲松治疗患者，临床可评价人群包括369例达托霉素治疗患者和371例头孢曲松治疗患者。在意向治疗人群中，达托霉素治疗的CAP患者的临床治愈率为70.9%，头孢曲松治疗的患者为77.4%（治愈率差异的95%置信区间为-12.4%至0.6%）。在临床可评价人群中，达托霉素治疗患者的临床治愈率（79.4%）低于头孢曲松治疗患者（87.9%;治愈率差异的95%置信区间为-13.8%至-3.2%）。事后分析显示，在接受有效治疗24 h的患者中，达托霉素治疗组（90.7%）和头孢曲松治疗组（88.0%;治愈率差异的95%置信区间为-6.1%至11.5%）的治愈率相似。达托霉素对CAP的治疗无效，包括肺炎链球菌和金黄色葡萄球菌引起的感染。观察结果表明，仅24小时的既往有效治疗可能会影响临床结局，这表明评价CAP治疗的试验可能需要排除入组前接受过任何潜在有效治疗的患者。
Objective. We sought to compare daptomycin with ceftriaxone for the treatment of patients with community-acquired pneumonia (CAP).Methods. Two phase-3 randomized, double-blind trials that enrolled adult patients hospitalized with CAP were conducted. Patients received intravenous daptomycin (4 mg/kg) or ceftriaxone (2 g) once daily for 5-14 days. Aztreonam could be added for patients with gram-negative infections. Clinical responses at the test-of-cure visit among patients in the intent-to-treat and clinically evaluable populations were the primary efficacy end points.Results. After combining data from the trials, the intent-to-treat population included 413 daptomycin-treated patients and 421 ceftriaxone-treated patients, and the clinically evaluable population included 369 daptomycin-treated patients and 371 ceftriaxone-treated patients. In the intent-to-treat population, the clinical cure rate among daptomycin-treated patients with CAP was 70.9%, compared with 77.4% among ceftriaxone-treated patients (95% confidence interval for the difference between cure rates, -12.4% to -0.6%). In the clinically evaluable population, the clinical cure rate was lower among daptomycin-treated patients (79.4%) than among ceftriaxone-treated patients (87.9%; 95% confidence interval for the difference between cure rates, -13.8% to -3.2%). A posthoc analysis revealed that, among those who had received up to 24 h of prior effective therapy, cure rates were similar among daptomycin-treated (90.7%) and ceftriaxone-treated patients (88.0%; 95% confidence interval for the difference between cure rates, -6.1% to 11.5%).Conclusions. Daptomycin is not effective for the treatment of CAP, including infections caused by Streptococcus pneumoniae and Staphylococcus aureus. The observation that as little as 24 h of prior effective therapy may impact clinical outcome suggests that trials to evaluate CAP treatment may need to exclude patients who have received any potentially effective therapy before enrollment.