Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer
Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer
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DOI：
10.1086/500139
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发表时间：
2006-03-01
影响因子：
11.8
通讯作者：
Tack, KJ
中科院分区：
文献类型：
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作者：
Jaksic, B;Martinelli, G;Tack, KJ
背景革兰氏阳性病原体可导致严重的感染，在血小板减少的癌症患者，万古霉素治疗往往是经验性的。利奈唑胺可能为这些患者提供一种选择。为了比较利奈唑胺和万古霉素在发热、贫血的癌症患者中的安全性和有效性，我们进行了一项双盲、多中心等效性研究。符合条件的经证实或疑似革兰氏阳性病原体感染的患者随机接受利奈唑胺或万古霉素治疗。完成治疗后7天的临床成功率（主要终点）在意向治疗（ITT）分析中两组之间等效（利奈唑胺，219/251例患者[87.3%];万古霉素，202/237例患者[85.2%]; 95% CI，-4.1至8.1; P = .52）、改良ITT分析、临床可评价分析和微生物学52逻辑可评价分析，以及按恶性肿瘤和感染类型分析的亚组之间。在改良ITT（6.6 vs. 8.5天;）和P = 0.04微生物学可评价子集（5.9 vs. 9.1天;）中，利奈唑胺的平均退热时间短于万古霉素，尽管事后分析显示恢复延迟P = 0.05。这些亚组中利奈唑胺的中性粒细胞绝对计数。在改良的ITT亚组（71例患者中的41例[57.7%] vs. 58例患者中的29例[ 50.0%]）和微生物学可评价亚组中，P = 0.05的微生物学成功率以及ITT亚组中的死亡率无组间差异（304例患者中的17例[5.6%]，P = 0.05）。38例患者vs. 301例患者中的23例[7.6%];）和所有亚组。不良事件的分布，包括报告的P =。31例血液学事件，两组之间相似，但利奈唑胺与药物相关不良事件较少（303例患者中52例[17.2%] vs. 300例患者中72例[24.0%];）和药物相关肾脏P =. 04例失败（1/303例患者[0.3%] vs. 7例患者[ 2.3%];）。P =. 04结论。利奈唑胺在发热性血小板减少的癌症患者中表现出与万古霉素相当的疗效和相似的安全性结局。
Background. Gram-positive pathogens can cause serious infections in neutropenic patients with cancer, and vancomycin therapy is often initiated empirically. Linezolid may offer an option for these patients.Methods. To compare the safety and efficacy of linezolid and vancomycin in febrile, neutropenic patients with cancer, we conducted a double-blind, multicenter equivalence study. Eligible patients with proven or suspected infection due to a gram-positive pathogen were randomized to receive linezolid or vancomycin.Results. Clinical success rates 7 days after completion of therapy ( primary end point) were equivalent between groups in the intent-to-treat (ITT) analysis ( linezolid, 219 [87.3%] of 251 patients; vancomycin, 202 [85.2%] of 237 patients; 95% CI, -4.1 to 8.1; P = .52), modified ITT analysis, clinically evaluable analysis, and microbiologically 52 logically evaluable analysis, as well as between subsets analyzed by malignancy and infection type. Mean time to defervescence was shorter for linezolid than vancomycin in the modified ITT ( 6.6 vs. 8.5 days;) and P = 04 microbiologically evaluable subsets (5.9 vs. 9.1 days;), although post hoc analyses revealed delayed recovery P =. 01 of absolute neutrophil counts for linezolid in these subsets. There were no between-group differences in P = .05 microbiologic success rates in the modified ITT subset ( 41 [57.7%] of 71 patients vs. 29 [ 50.0%] of 58 patients;) and microbiologically evaluable subsets, as well as in mortality rates in the ITT subset ( 17 [5.6%] of 304 P =. 38 patients vs. 23 [7.6%] of 301 patients;) and all subsets. Distribution of adverse events, including reported P =. 31 hematologic events, was similar between groups, except that linezolid was associated with fewer drug-related adverse events ( 52 [17.2%] of 303 patients vs. 72 [24.0%] of 300 patients;) and fewer cases of drug-related renal P =. 04 failure ( 1 [0.3%] of 303 patients vs. 7 [ 2.3%] of patients;). P =. 04Conclusions. Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer.