Abstract

Background

Clostridioides difficile infection (CDI) is a leading cause of hospital-associated antibiotic-related diarrhea and deaths worldwide. Vancomycin is one of the few antibiotics recommended for both nonsevere and severe CDI cases. We sought to determine whether vancomycin nonsusceptible C. difficile strains are circulating in the patient population.

Methods

Stool samples from patients with CDI were collected from 438 and 98 patients at a large university hospital in Houston, Texas, and Nairobi, Kenya, respectively. The stools were examined for the presence of vancomycin and metronidazole nonsusceptible C. difficile using broth dilution culture, Etest (BioMérieux, France), polymerase chain reaction (PCR), whole-genome sequencing, and in vivo testing in a CDI mouse model.

Results

Of the Houston stool samples, 114/438 (26%) had vancomycin nonsusceptible C. difficile isolates and 128/438 (29%) were metronidazole nonsusceptible. Similarly, 66 out of 98 (67%) and 83/98 (85%) of the Nairobi patients harbored vancomycin and metronidazole nonsusceptible isolates, respectively. Vancomycin treatment of a CDI mouse model infected with a vancomycin nonsusceptible isolate failed to eradicate the infection. Whole-genome sequencing analyses did not identify vanA genes, suggesting a different mechanism of resistance.

Conclusions

C. difficile strains exhibiting reduced susceptibility to vancomycin are currently circulating in patient populations. The spread of strains resistance to vancomycin, a first-line antibiotic for CDI, poses a serious therapeutic challenge. Routine susceptibility testing may be necessary.

中文翻译：

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对万古霉素敏感性降低的临床艰难梭菌分离株的出现

摘要

背景

艰难梭菌感染 (CDI) 是全世界医院相关抗生素相关性腹泻和死亡的主要原因。万古霉素是推荐用于非重度和重度 CDI 病例的少数抗生素之一。我们试图确定对万古霉素不敏感的艰难梭菌菌株是否在患者群体中传播。

方法

CDI 患者的粪便样本分别来自德克萨斯州休斯顿和肯尼亚内罗毕的一家大型大学医院的 438 名和 98 名患者。使用肉汤稀释培养法、Etest（BioMérieux，法国）、聚合酶链反应 (PCR)、全基因组测序和 CDI 小鼠模型体内测试，检查粪便中是否存在万古霉素和甲硝唑非敏感性艰难梭菌。

结果

在休斯顿的粪便样本中，114/438 (26%) 分离出万古霉素不敏感的艰难梭菌分离株，128/438 (29%) 分离出甲硝唑不敏感。同样，98 名内罗毕患者中的 66 名 (67%) 和 83/98 (85%) 分别携带万古霉素和甲硝唑不敏感分离株。用万古霉素不敏感分离株感染的 CDI 小鼠模型的万古霉素治疗未能根除感染。全基因组测序分析未识别出vanA基因，表明存在不同的耐药机制。

结论

表现出对万古霉素敏感性降低的艰难梭菌菌株目前正在患者群体中传播。对万古霉素（CDI 的一线抗生素）耐药的菌株的传播对治疗提出了严峻的挑战。可能需要进行常规药敏试验。