Emergence of reduced susceptibility to metronidazole in Clostridium difficile
Emergence of reduced susceptibility to metronidazole in Clostridium difficile
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DOI：
10.1093/jac/dkn313
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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：
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作者：
Baines, Simon D.;O'Connor, Rachael;Wilcox, Mark H.
目的：艰难梭菌感染（CDI）的抗菌治疗通常是甲硝唑，尽管有报道质疑这种选择的有效性。我们筛选了最近分离的艰难梭菌（2005-06）对甲硝唑的敏感性，并比较了历史分离株（1995-2001）的结果。方法：采用螺旋梯度终点分析法（SGE）筛选艰难梭菌001型（n = 86）、106型（n = 81）和027型（n = 48）以及利兹地区其他10种最常见的核型（n = 57）。以甲硝唑SGE MICs >= 6 mg/L为对照，采用琼脂掺入法和est法对艰难梭菌进行分析。对28株艰难梭菌进行了多位点可变数串联重复分析（MLVA）分型。结果：艰难梭菌核型106和027对甲硝唑的敏感性未见降低（几何平均SGE mic分别为1.11和0.90 mg/L）。相比之下，21株（24.4%）艰难梭菌001型对甲硝唑的敏感性降低（几何平均SGE mic为3.51 mg/L, P < 0.001）。观察到与方法和培养基有关的敏感性变化，但琼脂掺入法证实甲硝唑mic增加。历史上难辨梭菌001型核型（n = 72）的几何平均琼脂混合mic为1.03（范围0.25-2）mg/L，而最近对甲硝唑敏感性降低的分离株的几何平均mic为5.94 (4-8)mg/L （P < 0.001）。MLVA分型显示两个艰难梭菌克隆复合物，对甲硝唑的敏感性降低。结论：我们已经证明，在我们机构最近分离的艰难梭菌001型核型中，24.4%的人对甲硝唑的敏感性降低。我们的观察结果可能对临床环境有影响，因为甲硝唑进入结肠的渗透性差。
Objectives: Antimicrobial treatment for Clostridium difficile infection (CDI) has typically been metronidazole, although reports have questioned the efficacy of this option. We screened recently isolated C. difficile (2005-06) for susceptibility to metronidazole and compared results for historic isolates (1995-2001).Methods: C. difficile ribotypes 001 (n = 86), 106 (n = 81) and 027 (n = 48) and isolates from the 10 other most prevalent ribotypes in Leeds (n = 57) were screened using spiral gradient endpoint analysis (SGE). C. difficile with metronidazole SGE MICs >= 6 mg/L were analysed further by agar incorporation and Etest. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing was performed for 28 C. difficile isolates.Results: No reduced metronidazole susceptibility was observed in C. difficile ribotypes 106 and 027 (geometric mean SGE MICs 1.11 and 0.90 mg/L, respectively). In contrast, 21 (24.4%) C. difficile ribotype 001 demonstrated reduced susceptibility to metronidazole (geometric mean SGE MICs 3.51 mg/L, P < 0.001). Variations in susceptibility were observed relating to the method and media, but increased metronidazole MICs were confirmed by an agar incorporation method. Geometric mean agar incorporation MICs for historic C. difficile ribotype 001 (n = 72) were 1.03 (range 0.25-2) mg/L compared with 5.94 (4-8) mg/L (P < 0.001) for recent isolates displaying reduced metronidazole susceptibility. MLVA typing revealed two clonal complexes of C. difficile with reduced susceptibility to metronidazole.Conclusions: We have demonstrated the emergence of reduced susceptibility to metronidazole in 24.4% of the recent C. difficile ribotype 001 isolates from our institution. Our observations could have implications in the clinical setting due to the poor penetration of metronidazole into the colon.