In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile.
In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile.
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DOI：
10.1093/jac/dkv006
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Vickers RJ
中科院分区：
文献类型：
--
作者：
Corbett D;Wise A;Birchall S;Warn P;Baines SD;Crowther G;Freeman J;Chilton CH;Vernon J;Wilcox MH;Vickers RJ
SMT19969是一种正在临床开发中的新型抗菌药物，用于治疗艰难梭菌感染（CDI）。目的是确定 82 株艰难梭菌临床分离株（包括核糖型 027 分离株和甲硝唑敏感性降低的分离株）对 SMT19969、非达霉素、万古霉素和甲硝唑的比较敏感性，并确定 SMT19969、非达霉素和万古霉素对艰难梭菌的杀灭动力学和抗生素后效应。通过琼脂掺入测定 MIC。确定了针对艰难梭菌 BI1、630 和 5325（核糖型分别为 027、012 和 078）的杀伤动力学和抗生素后效应。 SMT19969 对艰难梭菌具有有效的抑制作用 (MIC90=0.125 mg/L)，并且比甲硝唑 (MIC90 = 8 mg/L) 或万古霉素 (MIC90 = 2 mg/L) 的活性明显更高。不同核糖体类型之间对SMT19969的敏感性没有差异。 Fidaxomicin 通常是比 SMT19969 活性高一倍的稀释液，并且两种药物均保持对分离株的活性，但对甲硝唑的敏感性降低。此外，SMT19969 对测试的艰难梭菌菌株具有杀菌作用，接种后 24 小时活菌计数减少至检测限以下。万古霉素对所有三种菌株均具有抑菌作用。 Fidaxomicin 具有杀菌作用，但与其他测试菌株相比，在 <20 × MIC 浓度下观察到对艰难梭菌 BI1（核糖型 027）的杀灭作用有所减少。这些数据表明，SMT19969 与针对测试菌株的有效杀菌活性相关，并支持进一步研究 SMT19969 作为 CDI 的潜在疗法。
SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C. difficile. MICs were determined by agar incorporation. Killing kinetics and post-antibiotic effects were determined against C. difficile BI1, 630 and 5325 (ribotypes 027, 012 and 078, respectively). SMT19969 showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L). There were no differences in susceptibility to SMT19969 between different ribotypes. Fidaxomicin was typically one doubling dilution more active than SMT19969 and both agents maintained activity against isolates with reduced susceptibility to metronidazole. In addition, SMT19969 was bactericidal against the C. difficile strains tested, with reductions in viable counts to below the limit of detection by 24 h post-inoculation. Vancomycin was bacteriostatic against all three strains. Fidaxomicin was bactericidal although reduced killing was observed at concentrations <20 × MIC against C. difficile BI1 (ribotype 027) compared with other strains tested. These data demonstrate that SMT19969 is associated with potent and bactericidal activity against the strains tested and support further investigation of SMT19969 as potential therapy for CDI.
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影响因子：
4.9
作者：
Goldstein EJ;Citron DM;Tyrrell KL;Merriam CV
通讯作者：
Merriam CV
影响因子：
5.2
作者：
Baines, Simon D.;O'Connor, Rachael;Wilcox, Mark H.
通讯作者：
Wilcox, Mark H.
影响因子：
14.2
作者：
Debast, S. B.;Bauer, M. P.;Kuijper, E. J.
通讯作者：
Kuijper, E. J.
DOI：
10.1093/cid/cit127
发表时间：
2013-06
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Walker AS;Eyre DW;Wyllie DH;Dingle KE;Griffiths D;Shine B;Oakley S;O'Connor L;Finney J;Vaughan A;Crook DW;Wilcox MH;Peto TE;Infections in Oxfordshire Research Database
通讯作者：
Infections in Oxfordshire Research Database
影响因子：
4.9
作者：
Louie, Thomas J.;Emery, Judy;Mah, Manuel
通讯作者：
Mah, Manuel