Thabit Abrar K, Alam M Jahangir, Khaleduzzaman Mohammed, Garey Kevin W, Nicolau David P
Center for Anti-infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA.
Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Ann Clin Microbiol Antimicrob. 2016 Apr 12;15:22. doi: 10.1186/s12941-016-0140-6.
To assess the effect of fidaxomicin and vancomycin on Clostridium difficile toxins and correlation with clinical and microbiologic outcomes.
Hospitalized patients with C. difficile infection were randomly assigned a 10-day course of fidaxomicin or vancomycin. Stool samples collected at baseline (day 0), mid-therapy (days 3-5), end of therapy (days 10-13) and follow-up (days 19-38) were assessed for quantity of toxins A and B as well as spore and vegetative cells counts. Correlation of toxins concentrations with microbiologic and clinical findings were evaluated.
Among 34 patients 12 had detectable toxin concentrations at baseline seven were randomized to fidaxomicin and five to vancomycin. Overall both fidaxomicin and vancomycin resulted in drop of both toxins concentrations by midpoint of therapy. The drop in toxin A concentrations was maintained up to the follow-up period with fidaxomicin but not with vancomycin even in patients who developed recurrence. Patients who developed recurrence in the fidaxomicin group had lower concentrations of toxin B versus the recurrence patient of vancomycin group. Presence of vegetative cells and spores was significantly linked with high toxin A (P = 0.003 and <0.001 respectively) and toxin B (P = 0.007 and <0.001 respectively) concentrations across time points. Toxin B concentrations but not A significantly correlated with stool consistency (P < 0.001) and frequency (P = 0.05).
Fidaxomicin was associated with sustained reduction of both toxins up to 30 days post therapy versus vancomycin. Multiple clinical or microbiologic observations were correlated with toxin A or B concentrations.
评估非达霉素和万古霉素对艰难梭菌毒素的影响及其与临床和微生物学结果的相关性。
将住院的艰难梭菌感染患者随机分配接受为期10天的非达霉素或万古霉素治疗。收集基线（第0天）、治疗中期（第3 - 5天）、治疗结束时（第10 - 13天）和随访期（第19 - 38天）的粪便样本，评估毒素A和B的含量以及芽孢和营养细胞计数。评估毒素浓度与微生物学和临床结果的相关性。
34例患者中，12例在基线时可检测到毒素浓度，7例随机接受非达霉素治疗，5例接受万古霉素治疗。总体而言，非达霉素和万古霉素在治疗中期均导致两种毒素浓度下降。非达霉素组毒素A浓度的下降在随访期内持续存在，而万古霉素组即使在复发患者中也未维持。非达霉素组复发患者的毒素B浓度低于万古霉素组复发患者。在各个时间点，营养细胞和芽孢的存在与高毒素A（分别为P = 0.003和<0.001）和毒素B（分别为P = 0.007和<0.001）浓度显著相关。毒素B浓度而非毒素A浓度与粪便稠度（P < 0.001）和频率（P = 0.05）显著相关。
与万古霉素相比，非达霉素与治疗后30天内两种毒素的持续降低有关。多种临床或微生物学观察结果与毒素A或B浓度相关。
