Background Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR). Methods This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016-2021. C. difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes. Results A high proportion (34%, 102/300) of C. difficile isolates exhibited reduced vancomycin susceptibility (range: 0.5-16 μg/mL, MIC50/90 = 2/4 μg/mL). Ribotype (RT) 027 accounted for the highest proportion (77.4%, 41/53) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76%, 78/102) than vancomycin susceptible strains (86%, 171/198; P=0.031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs. 96%; P=0.04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52, 95% confidence interval 0.28-0.97; P=0.04). Conclusions Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort.

中文翻译：

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艰难梭菌对万古霉素敏感性降低与初始治愈率和持续临床反应率较低相关

背景 流行病学研究表明临床艰难梭菌分离株对万古霉素的敏感性降低，但对患者预后的影响尚不清楚。我们假设万古霉素敏感性降低与持续临床反应（SCR）率降低相关。方法 这项多中心队列研究纳入了 2016 年至 2021 年间接受口服万古霉素治疗的艰难梭菌感染 (CDI) 成人。对艰难梭菌分离株进行了琼脂稀释万古霉素敏感性测试、核糖分型和万古霉素抗性 vanR 基因的桑格测序。降低的敏感性定义为万古霉素最低抑制浓度(MIC)＞2μg/mL。主要结局是 30 天 SCR；次要结局是 14 天初始治愈率、30 天复发率和 30 天死亡率。探索性分析评估了 VanR Thr115Ala 多态性、易感性和结果之间的关联。结果 高比例（34%，102/300）的艰难梭菌分离株表现出万古霉素敏感性降低（范围：0.5-16 μg/mL，MIC50/90 = 2/4 μg/mL）。核糖型（RT）027在万古霉素敏感性降低的分离株中所占比例最高（77.4%，41/53）。总体而言，83% (249) 的患者实现了 30 天的 SCR。与万古霉素敏感菌株（86%，171/198；P=0.031）相比，万古霉素敏感性降低与 30 天 SCR 率较低（76%，78/102）相关。在感染万古霉素敏感性降低菌株的个体中，还观察到 14 天初始治愈率显着降低（89% vs. 96%；P=0.04）。在多变量模型中，敏感性降低仍然是 30 天 SCR 的独立预测因素（优势比为 0.52，95% 置信区间为 0.28-0.97；P=0.04）。结论 在所研究的患者队列中，艰难梭菌万古霉素敏感性降低与 30 天 SCR 几率降低和 14 天初始治愈率降低相关。