Comparative Susceptibilities to Fidaxomicin (OPT-80) of Isolates Collected at Baseline, Recurrence, and Failure from Patients in Two Phase III Trials of Fidaxomicin against Clostridium difficile Infection
Comparative Susceptibilities to Fidaxomicin (OPT-80) of Isolates Collected at Baseline, Recurrence, and Failure from Patients in Two Phase III Trials of Fidaxomicin against Clostridium difficile Infection
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DOI：
10.1128/aac.00625-11
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发表时间：
2011-11-01
影响因子：
4.9
通讯作者：
Gerding, Dale N.
中科院分区：
文献类型：
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作者：
Goldstein, Ellie J. C.;Citron, Diane M.;Gerding, Dale N.
一种有效的大环状新药，口服非达克西星(200毫克，每日两次)，疗程10天，与万古霉素(125毫克，一天四次，每日四次)进行比较。在北美和7个欧洲国家的两个第三阶段随机双盲试验中，对1,164名成年人(改良意向治疗[Mitt]人群中的1,105人)艰难梭菌感染进行了研究。在1105名MITT患者中，792名(71.7%)，包括719/999(72.0%)的PP患者在基线时提供了艰难梭菌，其中356人接受了非达克索米星330次治疗(92.7%)，363人接受了万古霉素329次治疗(90.6%)。基线菌株的敏感度(MIC90)不能预测非达索米星(MIC90)的临床治愈、失败或复发(MIC90，两者的MIC90为0.25mU g/ml；范围为256mU g/ml)，两个治疗组在登记时均分离出菌株，治疗结束时失败的菌株增加到25%。在这两个III期研究中，治疗期间均未出现对非达克西星或万古霉素的耐药性，尽管从治愈患者身上分离出的单一菌株在复发时的非达克索米星最低抑菌浓度升高至16微克/毫升。所有菌株均对256微克/毫升的REA敏感，而对其他类型的REA较敏感。基线临床分离株的最低抑菌浓度与临床结果之间没有相关性。MIC(90)S对非达克星和万古霉素的MIC普遍较低，但BI分离株的MIC高于其他REA组分离株。
A 10-day course of oral fidaxomicin (200 mg twice a day [b.i.d.]), a potent new macrocyclic drug, was compared to vancomycin (125 mg four times a day [q.i.d.]) in 1,164 adults (1,105 in the modified intent-to-treat [mITT] population) with Clostridium difficile infection in two phase III randomized, double-blind trials at sites in North America and 7 European countries. Of 1,105 mITT patients, 792 (71.7%), including 719/999 (72.0%) in the per-protocol (PP) population, provided a C. difficile strain at baseline, of whom 356 received fidaxomicin with 330 cures (92.7%) and 363 received vancomycin with 329 cures (90.6%). The susceptibilities (MIC90) of baseline isolates did not predict clinical cure, failure, or recurrence for fidaxomicin (MIC90, 0.25 mu g/ml for both; range, 256 mu g/ml) strains were isolated in both treatment groups on enrollment, which increased to 25% for failures at the end of therapy. No resistance to either fidaxomicin or vancomycin developed during treatment in either of the phase III studies, although a single strain isolated from a cured patient had an elevated fidaxomicin MIC of 16 mu g/ml at the time of recurrence. All isolates were susceptible to 256 mu g/ml) than for the other REA types. There was no correlation between the MIC of a baseline clinical isolate and clinical outcome. MIC(90)s were generally low for fidaxomicin and vancomycin, but BI isolates had higher MICs than other REA group isolates.