儿童抗生素相关性艰难梭菌腹泻的病例对照研究

A case-control study of Clostridium difficile infection in children with antibiotic-associated diarrhea

目的探讨儿童抗生素相关性腹泻(AAD)中艰难梭菌感染(CDI)的发生情况及临床特点,为抗生素相关CDI的诊治提供依据。方法纳入2016年6月1日至2017年10月1日在复旦大学附属儿科医院行CD毒素A/B检测和CD厌氧培养且符合AAD诊断标准的住院患儿,排除<1月龄、粪便常规细菌培养和病毒检测等临床信息不完整的病例,重复病例仅纳入首次诊断AAD时的临床信息。毒素A/B检测阳性或结肠镜检查提示假膜性肠炎者CDI组;余为非CDI组。单人从病志中采集一般资料,基础疾病,出现AAD相关腹泻症状前2个月内的抗生素使用情况,1个月内的治疗和药物使用情况,实验室指标等。结果符合本文纳入标准的AAD患儿150例,年龄40 d至15岁2月,中位年龄1.4岁,男103例(68.7%)。CDI组24例(16.0%),非CDI组126例。(1)CDI组急性腹泻22例(中位腹泻天数8 d),因克罗恩病导致的慢性腹泻急性加重1例;因结肠息肉导致的迁延性腹泻急性加重1例,发热11例(45.8%),呕吐8例(33.3%),腹痛2例(8.3%),腹胀1例(4.2%);1例(1/5,20%)结肠镜显示为伪膜性肠炎。(2)CDI组和非CDI组发病年龄,性别,基础疾病,腹泻前2个月内抗生素应用情况,腹泻前1个月内手术或糖皮质激素、免疫抑制剂和抑酸药应用情况,实验室指标差异无统计学意义(P>0.05)。多因素logistic分析显示CDI和非CDI临床表现和常规实验室检测指标差异无统计学意义(P>0.05)。(3)AAD的主要治疗措施为停用广谱抗生素,益生菌辅助治疗,CDI患儿症状无好转时加用甲硝唑(应用5~7 d后未见明显好转改口服万古霉素)。CDI组腹泻均好转或痊愈,非CDI组117例(94.4%)腹泻症状好转,9例死于腹泻外的其他原因。结论儿童AAD中CDI发生率为16.0%,发热、呕吐为最常见的临床表现,经治疗后预后良好,仅凭临床表现和实验室检测指标不能区分儿童ADD中CDI和非CDI。

Objective To investigate the incidence and clinical characteristics of Clostridium difficile infection(CDI)in children with antibiotic-associated diarrhea(AAD),and to provide evidence for the diagnosis and treatment of antibiotic-related CDI.Methods Inpatient clinical data of antibiotic-associated diarrhea from June1st2016to October1st2017were collected in Children's Hospital of Fudan University.Toxin A/B were tested and Clostridium difficile(CD)was cultured.Neonates,incomplete information such as lack of fecal conventional bacteria culture and virus detection and the repeated cases were excluded.Toxin A/B(+)or the colonoscopy suggested pseudomembranous colitis cases were CDI group,the rest were in non-CDI group.Results There were150patients with AAD.The incidence of CDI was16.0%(24/150).The onset age of diarrhea was from one month ten days to15years2months old(median age1.4years old),among them boys were103(68.7%)cases.①Among24CDI patients,22children had acute diarrhea,1had aggravated chronic diarrhea,because of Crohn's disease,1had transitive diarrhea due to rectal polyp,11(45.8%)had fever,8(33.3%)had vomitus,2(8.3%)had abdominal pain,1had abdominal distension,1had pseudomembranous colitis.②There was no significant difference(P>0.05)in age of onset of diarrhea,gender,concomitant disease and antibiotic therapy two months before diarrhea between CDI group and non-CDI group.There was no statistic difference(P>0.05)in operations history,glucocorticoids and acid inhibitors therapy one month before suffering from diarrhea and lab index.The multiple factors Logistic models showed that clinical characteristics and routine laboratory test indicators had no statistically significant diffierence(P>0.05)between CDI group and non-CDI group.③The main treatments of AAD were to discontinue the broad-spectrum antibiotics,probiotics adjuvant therapy.If symptoms of CDI patients were not improved,metronidazole was the first choice.Failure to respond to metronidazole within5-7days should chang to vancomycin(oral)at standard dosing.The patients with symptomatic treatments of diarrhea were relieved in all CDI group,117were improved in non-CDI group,9died of non-diarrhea.Only clinical performance and routine laboratory test indicators can't distinguish CDI and non-CDI among children AAD.Conclusion The incidence of CDI of AAD patients was16.0%.Fever and vomiting were the most common manifestations and prognosis was good.Only clinical performance and routine laboratory test indicators can't distinguish CDI and non-CDI among children AAD