在一项针对癌症发热性中性粒细胞减少患者的随机双盲研究中，利奈唑胺与万古霉素相比的疗效和安全性。
Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer.
作者信息
Jaksic Branimir, Martinelli Giovanni, Perez-Oteyza Jaime, Hartman Charlotte S, Leonard Linda B, Tack Kenneth J
机构信息
Department of Medicine, Merkur University Hospital, Zagreb, Croatia.
出版信息
Clin Infect Dis. 2006 Mar 1;42(5):597-607. doi: 10.1086/500139. Epub 2006 Jan 25.
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 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; P=.04) and microbiologically evaluable subsets (5.9 vs. 9.1 days; P=.01), although post hoc analyses revealed delayed recovery of absolute neutrophil counts for linezolid in these subsets (P<.05). There were no between-group differences in microbiologic success rates in the modified ITT subset (41 [57.7%] of 71 patients vs. 29 [50.0%] of 58 patients; P=.38) and microbiologically evaluable subsets, as well as in mortality rates in the ITT subset (17 [5.6%] of 304 patients vs. 23 [7.6%] of 301 patients; P=.31) and all subsets. Distribution of adverse events, including reported 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; P=.04) and fewer cases of drug-related renal failure (1 [0.3%] of 303 patients vs. 7 [2.3%] of patients; P=.04).
CONCLUSIONS
Linezolid demonstrated efficacy and similar safety outcomes equivalent to those for vancomycin in febrile neutropenic patients with cancer.
背景
革兰氏阳性病原体可在癌症中性粒细胞减少患者中引起严重感染，万古霉素治疗通常是经验性开始。利奈唑胺可能为这些患者提供一种选择。
方法
为比较利奈唑胺和万古霉素在发热性癌症中性粒细胞减少患者中的安全性和疗效，我们进行了一项双盲、多中心等效性研究。因革兰氏阳性病原体导致已证实或疑似感染的符合条件患者被随机分配接受利奈唑胺或万古霉素治疗。
结果
在治疗完成7天后的临床成功率（主要终点）在意向性分析（ITT）中两组相当（利奈唑胺组，251例患者中的219例[87.3%]；万古霉素组，237例患者中的202例[85.2%]；95%CI，-4.1至8.1；P = 0.52），在改良ITT分析、临床可评估分析和微生物学可评估分析中以及按恶性肿瘤和感染类型分析的亚组之间也是如此。在改良ITT（6.6天对8.5天；P = 0.04）和微生物学可评估亚组（5.9天对9.1天；P = 0.01）中，利奈唑胺的平均退热时间比万古霉素短，尽管事后分析显示这些亚组中利奈唑胺的绝对中性粒细胞计数恢复延迟（P<0.05）。在改良ITT亚组（71例患者中的41例[57.7%]对58例患者中的29例[50.0%]；P = 0.38）和微生物学可评估亚组中的微生物学成功率以及ITT亚组（304例患者中的17例[5.6%]对301例患者中的23例[7.6%]；P = 0.31）和所有亚组中的死亡率在组间均无差异。不良事件的分布，包括报告的血液学事件，在组间相似，只是利奈唑胺与较少的药物相关不良事件（303例患者中的52例[17.2%]对300例患者中的72例[24.0%]；P = 0.04）以及较少的药物相关肾衰竭病例（303例患者中的1例[0.3%]对300例患者中的7例[2.3%]；P = 0.04）相关。
结论
在发热性癌症中性粒细胞减少患者中，利奈唑胺显示出与万古霉素相当的疗效和相似的安全性结果。
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