RM Alden Research Lab, Culver City, CA, USA.
Anaerobe. 2009 Dec;15(6):234-6. doi: 10.1016/j.anaerobe.2009.09.005. Epub 2009 Sep 12.
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.
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.
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 MIC(90) values for the three antibiotics tested, but the MIC(90) of BI strains was two dilutions higher than non-BI strains for metronidazole and vancomycin (for both antibiotics, MIC(90) was 2 microg/mL vs. 0.5 microg/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%).
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.
近年来，艰难梭菌感染（CDI）的发病率和严重程度一直在增加，这与一种“高毒力”菌株——REA 型 BI（核糖体分型 027，PFGE NAP 1）的传播相一致。使问题更加严重的是，观察到甲硝唑的疗效可能正在下降，尤其是在更严重的病例中。非达霉素是一种 18 元大环内酯类化合物，目前正在进行治疗艰难梭菌感染（CDI）的 3 期临床试验。一项 CDI 患者的开放性、2 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出艰难梭菌，并通过限制性内切酶分析（REA）对其进行分型，以确定艰难梭菌分离株的频率和敏感性及其对治疗的反应。
将粪便样本接种于 CCFA 琼脂上，以分离艰难梭菌。使用 CLSI 琼脂稀释法检测这些分离株对非达霉素、万古霉素和甲硝唑的敏感性，并通过 REA 进行分型。
从 49 名受试者中的 38 名中分离出艰难梭菌，其中 16 名（42%）为流行的 BI 组艰难梭菌。BI 株在三个剂量组中的分布大致相同。总体抗生素敏感性与之前报道的三种抗生素的 MIC（90）值一致，但 BI 株对甲硝唑和万古霉素的 MIC（90）比非 BI 株高两个稀释度（甲硝唑 MIC（90）为 2μg/ml 对 0.5μg/ml，P<0.01；万古霉素 MIC（90）为 2μg/ml 对 0.5μg/ml，P=NS）。BI 分离株的临床治愈率（11/14，79%）与非 BI 分离株（21/22，95%）无显著差异。
这些结果突出了 BI 流行株的高患病率，并表明轻度至中度 CDI 感染以及严重疾病都可能由这些菌株引起。非达霉素治疗 BI 株和非 BI 株受试者的治愈率相似，尽管受试者数量较少，无法进行稳健的统计学比较。
