Comparison of oritavancin versus vancomycin as treatments for clindamycin-induced Clostridium difficile PCR ribotype 027 infection in a human gut model
Comparison of oritavancin versus vancomycin as treatments for clindamycin-induced Clostridium difficile PCR ribotype 027 infection in a human gut model
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DOI：
10.1093/jac/dkn358
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发表时间：
2008-11-01
影响因子：
5.2
通讯作者：
Wilcox, Mark H.
中科院分区：
文献类型：
--
作者：
Baines, Simon D.;O'Connor, Rachael;Wilcox, Mark H.
目的：比较奥利万星和万古霉素在治疗艰难梭菌感染（CDI）的有效性，使用在体外human gut model.Methods：我们诱导CDI滴注克林霉素到体外肠道模型与汇集的人粪便和C。difficile ribotype 027孢子。奥利万星和万古霉素在单独的实验中滴入，其水平相当于患者粪便中预期的水平（万古霉素）或受药物溶解度限制的水平（奥利万星）。艰难梭菌增殖和高水平的细胞毒素产生。万古霉素滴注降低了植物性C。1天内的艰难梭菌数量，但不影响C.艰难孢子奥利万星滴注可显著降低C.在2天内将艰难的营养体数量和孢子降至检测限以下。在滴注奥利万星或万古霉素后，两个实验中的细胞毒素滴度均下降至检测限，但在万古霉素实验中下降更快（5天内）。停止万古霉素滴注与进一步的C。艰难梭菌增殖和高水平的细胞毒素产生。相反，停止奥利万星后没有观察到毒素复发。结论：奥利万星和万古霉素在人肠道模型中治疗克林霉素诱导的CDI有效，但只有奥利万星对孢子形式的C。很难此外，万古霉素滴注后观察到高水平细胞毒素产生的复发，但奥利万星未观察到。奥利万星可能比万古霉素更能治疗CDI，这可能是因为奥利万星可以预防C.艰难孢子
Objectives: To compare the efficacy of oritavancin and vancomycin in the treatment of Clostridium difficile infection (CDI) using an in vitro human gut model.Methods: We induced CDI by instilling clindamycin into an in vitro gut model primed with pooled human faeces and C. difficile ribotype 027 spores. Oritavancin and vancomycin were instilled in separate experiments at levels equivalent to those expected in the faeces (vancomycin) of patients or levels limited by the solubility of the drug (oritavancin).Results: Clindamycin exposure elicited C. difficile proliferation and high-level cytotoxin production in both experiments. Vancomycin instillation reduced vegetative C. difficile numbers within 1 day but did not affect the numbers of C. difficile spores. Oritavancin instillation markedly reduced C. difficile vegetative numbers and spores to below the limits of detection within 2 days. Cytotoxin titres in both experiments declined to the limits of detection after instillation with oritavancin or vancomycin, but did so more quickly (within 5 days) in the vancomycin experiment. Cessation of vancomycin instillation was associated with further C. difficile proliferation and high-level cytotoxin production. Conversely, toxin recrudescence was not observed following cessation of oritavancin.Conclusions: Both oritavancin and vancomycin were effective in treating clindamycin-induced CDI in a human gut model, but only oritavancin appeared active against spore forms of C. difficile. Furthermore, recurrence of high-level cytotoxin production was observed following vancomycin instillation but not oritavancin. Oritavancin therapy may be more in treating CDI than vancomycin, possibly because it may prevent recrudescence of C. difficile spores.