Typing and susceptibility of bacterial isolates from the fidaxomicin (OPT-80) phase II study for C. difficile infection
Typing and susceptibility of bacterial isolates from the fidaxomicin (OPT-80) phase II study for C. difficile infection
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DOI：
10.1016/j.anaerobe.2009.09.005
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发表时间：
2009-12-01
期刊：
影响因子：
2.3
通讯作者：
Gerding, D. N.
中科院分区：
文献类型：
--
作者：
Citron, D. M.;Babakhani, F.;Gerding, D. N.
背景：艰难梭菌感染(CDI)的发病率和严重程度近年来一直在增加，这与一种超强毒力菌株REA BI(ribotype 027，PFGE NAP 1)的传播是一致的。使这一问题恶化的是，观察到甲硝唑可能表现出疗效下降，特别是在更严重的病例中。非达索米星是一种由18个成员组成的大环，目前正处于治疗艰难梭菌感染(CDI)的3期试验中。一项针对CDI患者的开放式II期研究已经完成，并公布了临床结果。从患者粪便标本中分离艰难梭菌，用限制性内切酶分析(REA)进行分型，以确定艰难梭菌的分离频率、敏感性和对治疗的反应。用CLSI琼脂稀释法检测分离株对非达克星、万古霉素和甲硝唑的敏感性，并用放射免疫法进行分型。结果：49例受试者中有38例分离到艰难梭菌，其中16例(42%)为艰难梭菌BI流行群。BI菌株在三个剂量组中大致均匀分布。三种抗生素的总体药敏结果与文献报道的MIC90值基本一致，但BI株对甲硝唑和万古霉素的MIC90比非BI株高2倍(甲硝唑MIC90为2mUg/mLvs.0.5mUg/ml，P=0.01NS万古霉素)。临床治愈的BI分离株(11/14，79%)与非BI分离株(21/22，95%)无显著差异。结论：这些结果强调了BI流行株的高流行率，并表明这些菌株可引起轻至中度的CDI感染和严重的疾病。患有BI和非BI菌株的受试者的非达克索米星治愈率相似，尽管受试者的数量很少，因此无法进行强有力的统计比较。(C)2009爱思唯尔有限公司。保留所有权利。
Background: Clostridium difficile infection (CDI) has been increasing in incidence and severity in recent years, coincident with the spread of a "hypervirulent" strain, REA type BI (ribotype 027, PFGE NAP 1). Exacerbating the problem has been the observation that metronidazole may be showing decreased effectiveness, particularly in the more severe cases. Fidaxomicin is an 18-membered macrocycle currently in phase 3 trials for the treatment of C. difficile infection (CDI). An open-label, phase II study in CDI patients has been completed and the clinical results published. C. difficile organisms were isolated from patient stool specimens and typed by restriction endonuclease analysis (REA) in order to determine the frequency and susceptibility of the C. difficile isolates and their response to treatment.Methods: Fecal samples were plated on CCFA agar for isolation of C. difficile. These isolates were tested for susceptibility to fidaxomicin, vancomycin, and metronidazole using CLSI agar dilution methods and were typed by REA.Results: C. difficile was isolated from 38 of 49 subjects and 16 (42%) were the epidemic C. difficile BI group. The BI strain was distributed approximately equally in the three dosing groups. Overall antibiotic susceptibilities were consistent with the previously reported MIC90 values for the three antibiotics tested, but the MIC90 of BI strains was two dilutions higher than non-BI strains for metronidazole and vancomycin (for both antibiotics, MIC90 was 2 mu g/mL vs. 0.5 mu g/ml, P < 0.01 for metronidazole, P = NS for vancomycin). Clinical cure for BI isolates (11/14, 79%) was not significantly different from non-BI isolates (21/22, 95%).Conclusion: These results underscore the high prevalence of the BI epidemic strain and demonstrate that mild to moderate CDI infection as well as severe disease can be caused by these strains. Fidaxomicin cure rates for subjects with BI and with non-BI strains are similar, although the small numbers of subjects preclude a robust statistical comparison. (C) 2009 Elsevier Ltd. All rights reserved.