艰难梭菌（Clostridium difficile）是抗生素相关腹泻的重要病因，其临床表现轻重不一，包括无症状定植或轻度腹泻，也可表现为肠梗阻、中毒性巨结肠、低血压或休克为特征的暴发性疾病。尽管儿童艰难梭菌感染相较于成人少见，但其发生率正在增加。在第33届欧洲临床微生物学和感染病学大会（ECCMID 2023）的一场大会报告中，专家们讨论了儿童艰难梭菌感染（CDI）的诊疗进展。《国际肝病》在现场采访了报告讲者之一、休斯敦大学药学实践和转化研究学系的Anne Gonzales-Luna教授。

 

 

https://mp.weixin.qq.com/s/1gP1riWsLY8261eNKP7Zmw

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01

《国际肝病》：导致儿童艰难梭菌感染（CDI）的原因是什么？

 

Gonzales-Luna教授：艰难梭菌是一种胃肠道感染细菌。它在患者中定植，并通过扩大其生态位（niche）在易感宿主中致病。它产生芽孢而成为产生毒素的营养细胞，这些毒素会对肠道和肠黏膜造成大量损伤，导致腹泻和腹痛的主要症状。有时患者可能会有更严重的感染，导致毒性巨结肠或伪膜性结肠炎。这种病理生理学表现在成人和儿童中是相同的。在儿童身上，确实可以看到易感染艰难梭菌的人群，这与我们在成年人身上看到的不同。在成年人中，主要的风险因素是老年和抗生素暴露。在儿童中，往往会看到患有艰难梭菌感染的儿童具有潜在的免疫缺陷，如癌症，或有破坏肠道正常防御系统的慢性胃肠道疾病。

 

IDF: What causes Clostridioides difficile infection in children? 

 

Dr Gonzales-Luna: Clostridioides difficile is a gastrointestinal infection. Clostridioides difficile is a bacteria. It colonizes patients and causes disease in susceptible hosts by expanding its niche. It germinates into vegetative cells that produce toxins, and those toxins cause a lot of damage to the intestine and intestinal mucosa. That leads to primary symptoms of diarrhea and abdominal pain primarily. Sometimes patients can have more severe infections that cause toxic megacolon or pseudomembranous colitis. This pathophysiology is the same in both adults and children. In children, you do see populations that are susceptible to C. difficile infection that are different to what we see in adults. In adults, the primary risk factors are old age and antibiotic exposure. In children, you tend to see children who get C. difficile infection (CDI) have underlying immunodeficiencies, such as cancer, or have chronic GI conditions that disrupt to usual defense systems in the gut.

 

02

《国际肝病》：儿童艰难梭菌感染的主要治疗建议是什么？

 

Gonzales-Luna教授：美国有IDSA-SHEA指南，而欧洲唯一涉及儿科建议的（ESCMID）指南实际上是从2014年开始的。在这两个指南发表时，我们真的没有太多的比较数据，也没有太多支持儿童使用任何一种抗生素的总体数据。在这些指南中，甲硝唑和万古霉素同样被推荐用于治疗艰难梭菌感染、非严重感染以及初次或复发感染。自从这些指南发表以来，我们实际上已经进行了一项比较万古霉素和非达霉素（fidaxomicin）的随机对照试验。实际上这两种抗生素的治愈率相当，但非达霉素的全球治愈率（包括复发）确实更高。因此，当你观察一个更长的终点时，你会发现这些儿童在抗生素治疗后是否会复发，有数据确实支持非达霉素。

 

IDF: What are the recommendations for treatment of Clostridioides difficile infection in children? 

 

Dr Gonzales-Luna: There are IDSA-SHEA Guidelines in the United States, and the only guidelines in Europe that address pediatric recommendations are actually from 2014. At the time of publication for either of those guidelines, we really didn’t have much comparative data and really much data in general supporting any one antibiotic in children. In those guidelines, metronidazole and vancomycin are recommended equally for treatment of C. difficile infection for non-severe infections, and for initial or recurrent infections. Since those guidelines were published, we actually now have a randomized controlled trial comparing vancomycin and fidaxomicin. The two of those antibiotics actually had equivalent rates of cure, but fidaxomicin did have a higher rate of global cure, which encompasses recurrence. So when you look at a longer end-point, and you see whether these children develop recurrence following antibiotic treatment, there data really favors fidaxomicin.

 

03

《国际肝病》：儿童艰难梭菌感染的治疗面临哪些挑战？

 

Gonzales-Luna教授：我认为儿童面临的最大挑战是确保你能正确诊断他们。1岁或2岁以下的儿童有很高的无症状定植率。因此，如果使用诊断性PCR（聚合酶链反应）或NAAT（核酸扩增检测），你很可能会发现存在艰难梭菌定植，但不一定会导致感染，所以你会看到CDI的发病率被高估。考虑到这一挑战（确保正确诊断儿童），这确实使临床试验的开展和解释变得复杂，并破坏了我们现有的许多证据。由于这些误诊，很难追踪儿童CDI的发病率，也很难评估这些儿童的预后。

 

IDF: What challenges are there in the treatment of pediatric Clostridioides difficile infection?

 

Dr Gonzales-Luna: I think the biggest challenge in children is ensuring you are correctly diagnosing them. Children less than 1 or 2 years old have really high rates of asymptomatic colonization. So if using a diagnostic PCR or NAAT, you are likely going to find C. difficile present that may not be causing infection, so you will see over-estimation of the rates of CDI. With that challenge in mind (making sure you are correctly diagnosing children), it really complicates clinical trial conduction and interpretation, and undermines a lot of the evidence we do have. It is difficult to track the incidence of CDI in children because of these misdiagnoses, and it is difficult to assess outcomes in these children.

编辑：Fangfei Chen