益生菌在儿童抗生素相关性腹泻病的应用

儿童抗生素相关性腹泻(AAD)是指抗生素扰乱和破坏肠道菌群稳态,是儿科临床上最为常见的副反应。艰难梭菌相关性腹泻(CDAD)是AAD中的严重结肠炎类型。抗生素造成肠道菌群的结构改变,多样性减少,菌群组成结构重新分布;宿主肠黏膜免疫应答模式变化,开放病原菌侵入结合位点,诱导耐抗生素机会菌株的定植,感染易感性增高;菌群构成改变,干扰糖和胆汁酸代谢等原因引起腹泻。益生菌早期干预可以有效减低AAD和CDAD的发生率,临床上在使用抗生素同时应用益生菌是合理有效的。     

深圳地区2004-2006年儿童腹泻病病原体分布情况

目的 探讨深圳地区2004-2006年儿童腹泻病病原体分布情况.方法 收集深圳地区2004年1月-2005年4月腹泻病患儿粪便标本,采用ELISA法检测轮状病毒(RV),2005年5月-2006年12月采用胶体金法检测RV.真菌性腹泻以40倍高倍镜下同时可见菌丝和孢子为实验诊断标准.阿米巴性腹泻以见溶组织内活动性阿米巴原虫(滋养体或包囊)为实验诊断标准.细菌性腹泻(菌痢)以40倍高倍镜下WBC( )以上,同时可见RBC为实验诊断标准.不确定性腹泻为排除以上4种腹泻外的腹泻.结果 RV腹泻主要发生在10月至次年2月,但夏季6-7月也有一个小高峰,共占40.49%;真菌性腹泻无明显季节性,占3.59%;细菌性腹泻明显在每年的6-9月高发,占39.67%;阿米巴性腹泻仅检测到10例,除1例是春末检测出来外,余皆在夏季检出,占0.03%;不确定性腹泻主要发生在12月至次年的3月,占16.24%.腹泻最高发年龄为＞1～2岁,占24.83%(8 287/33 382例),≤6个月组为最低发年龄组,占6.65%(2 217/33 382例).结论 婴幼儿腹泻种类出现明显的感染交叉性、季节交叉性的特点,具有一定的复杂多样性.加强饮食与环境卫生,切断传播途径,提高儿童主动免疫水平是预防急性腹泻的重要环节.     

急性轮状病毒腹泻患儿外周血单核细胞Toll样受体3 mRNA表达及血清γ干扰素和肿瘤坏死因子α水平

目的 探讨外周血单核细胞Toll样受体3(TLR3)mRNA表达与急性轮状病毒(RV)腹泻的关系.方法 选取61例急性RV腹泻患儿为研究对象,以实时荧光定量RT-PCR检测外周血单核细胞TLR3 mRNA表达,采用ELISA法检测血清IFN-γ、TNF-α,水平.结果 重型腹泻组外周血单核细胞TLR3 mRNA表达及血清IFN-γ、TNF-α水平分别为0.820±0.051、(33.67±12.88)pg/ml、(62.21±14.65)pg/ml,而轻型腹泻组为0.717±0.040、(24.01±10.06)pg/ml、(50.99±12.18)pg/ml,正常对照组为0.525±O.029,(12.52±5.19)pg/ml、(28.65±7.44)pg/ml.与正常对照组相比,重型和轻型腹泻组TLR3 mRNA表达及血清IFN-γ、TNF-α水平明显升高,差异有非常显著性(P<0.01),重型腹泻组与轻型腹泻组相比,差异有非常显著性(P<0.01).外周血单核细胞TLR3表达和血清IFN-γ、TNF-α水平呈正相关(r=0.431,P<0.05,r=0.372,P<0.05).结论 急性RV腹泻患儿外周血单核细胞TLR3 mRNA表达上调,TLR3及其介导的免疫应答与急性RV腹泻的发生发展存在一定的相关性.     

小儿感染性腹泻的液体疗法

根据病原体致泻作用的不同,感染性腹泻可分为:分泌性腹泻,即肠毒素性腹泻;渗透性腹泻,即吸水障碍性腹泻;侵袭性腹泻,即炎症性腹泻。在进行液体疗法之前,必需细致观察脱水的程度和体征,化验血中电解质含量及酸硷失衡情况,以及病原学检测,包括细菌、病毒等。要做到心中有数,考虑全面,做出正确的液疗方案。口服补液疗法(oral rehydration theory,ORT) 根据小肠上皮细胞朝向肠腔一侧的刷状缘上,存     

儿童抗生素相关性艰难梭菌腹泻的病例对照研究

摘要 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。①CDI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。②CDI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)。③AAD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。     

上海城乡结合部急性腹泻病儿童的病原及转归

目的探讨上海城乡结合部小儿急性腹泻病的病原及转归,为该区腹泻病的防治提供参考。方法收集2005年12月-2006年11月本院儿科门诊的急性腹泻患儿资料。病程<7d,大便次数>3次/d,每例均详细询问病史和体格检查,行脱水情况评估,大便镜检。大便镜检WBC10/HP以上者行细菌培养、轮状病毒检测,根据病原分组给予相应治疗,指导家属记录症状日记卡,并行病程随访,资料均采用SPSS13.0进行统计分析。结果共纳入急性腹泻患儿314例。男193例,女121例,男女比例为1.6∶1.0;年龄42d～11岁。其中侵袭性(INV)腹泻77例(24.5%),轮状病毒(RV)腹泻106例(33.8%),抗生素相关性腹泻(AAD)19例(6.1%),食物不耐受(FI)腹泻48例(15.3%),原因不明性腹泻64例(20.4%)。止泻时间:INV腹泻(29.1±10.8)h,RV腹泻(113.7±49.2)h,AAD腹泻(83.0±25.8)h,FI腹泻(67.0±20.1)h,原因不明性腹泻(76.0±20.3)h。INV腹泻止泻时间短,0.5a后再次腹泻发生率较低(11.7%),而RV腹泻平均止泻时间0.5a内再次腹泻发生率最高(43.5%)。结论与1996-1998年比较,本地区INV腹泻的发病率显著下降,RV腹泻发生率上升。RV腹泻止泻时间最长,0.5a内再次腹泻发生率较其他原因腹泻更多见。AAD的发生率也明显升高,在诊治中应重视病原学诊断和合理使用抗生素。     

新生儿轮状病毒肠炎及继发乳糖酶缺陷临床分析

为探讨新生儿腹泻中轮状病毒性肠炎及继发性乳糖酶缺陷的发病情况及临床特点.采用EILASA快速轮状病毒抗原检测方法及醋酸铅法,对38例确诊为轮状病毒性肠炎的病例进行总结分析.51例新生儿腹泻,轮状病毒抗原检测阳性38例(74.51%),而在确诊为轮状病毒性肠炎38例中,大便乳糖阳性37例(97.37%).结果提示,在秋冬季节,轮状病毒是新生儿腹泻的首位病原,而新生儿轮状病毒肠炎绝大多数有继发性乳糖酶缺陷.     

多重感染致儿童急性腹泻病的多中心临床研究

目的 观察急性腹泻患儿中单一感染与混合感染的发病率,比较单一和多个病原体感染患儿的临床表现.方法 采用回顾性研究方法,选择年龄1个月～14岁诊断急性腹泻病的患儿4728例作为观察对象.单一感染组和混合感染组患儿均进行大便常见病原体检测,包括轮状病毒(rotavirus,RV)、肠道腺病毒(enteric adenovirus,EAdV)、诺如病毒(norovirus,NV)抗原以及常见肠道致病菌的培养、分离鉴定.同时观察患儿病情的严重程度,包括腹泻持续时间和频率,发热、呕吐持续时间以及脱水的程度.结果 4 728例患儿中有一种及一种以上病原体感染的有3 595例(76.0％),实验室检测未发现病原体感染的患儿有1 133例(24.0％).其中RV感染有1 889例(40.0％),EAdV有412例(8.7％),NV感染有309例(6.5％),大肠埃希菌(VTEC) 274例(5.8％),沙门菌属276例(5.8％),肺炎克雷伯菌感染123例(2.6％),志贺菌78例(1.6％),金黄色葡萄球菌70例(1.5％)和产气荚膜杆菌126例(2.7％).其中1370例(29.0％)腹泻患儿存在混合感染,以RV合并NV感染150例(3.2％)及RV与产气荚膜菌混合感染127例(2.7％)为最常见.混合感染所致的儿童急性腹泻较单一感染临床表现更加严重,差异有统计学意义(P＜0.05).结论 轮状病毒仍是儿童急性腹泻最常见的病原体,其次为NV、EAdV、沙门菌属及VTEC.混合感染中轮状病毒合并诺如病毒感染最常见.在病毒与细菌混合感染时,VTEC与各类病毒合并感染发生率最高.多种病毒感染与单一病毒感染腹泻患儿比较,呕吐持续时间和脱水程度较严重,而发热及腹泻持续时间、腹泻频率则无明显差异.病毒合并细菌感染与单一病毒感染和单一细菌感染腹泻患儿的临床表现比较,混合感染患儿发热、呕吐及腹泻持续时间长,腹泻、脱水程度都更加严重.     

锌佐治婴幼儿迁延性腹泻的临床研究

目的：探讨迁延性腹泻患儿血、尿锌水平的变化及补锌对迁延性腹泻患儿的临床疗效。方法：测定迁延性腹泻患儿血、尿锌浓度及尿锌与肌酐比值(Zn/Cr)判断其体内锌状态。将124例患儿分为两组,即补锌组60例与非补锌组64例,观察治疗前后两组尿Zn/Cr值的变化及疗效的差异。结果：①迁延性腹泻患儿与正常健康儿对比,血锌浓度分别为(1.02±0.18) μg/ml与(1.20±0.17) μg/ml(P<0.01);尿锌浓度分别为(0.412±0.253) μg/ml与(0.612±0.215) μg/ml(P<0.01);尿Zn/Cr值分别为(0.51±0.19)×10-3与(0.72±0.21)×10-3(P<0.01)。②治疗后尿Zn/Cr值补锌组与非补锌组分别为(0.71±0.22)×10-3与(0.48±0.17)×10-3(P<0.01)。③两组治愈率：补锌组为80%(48/60),非补锌组为 59.4%(38/64),(P<0.01)。两组疗程分别为补锌组(8.1±3.2) d,非补锌组(9.8±3.8) d,(P<0.01)。④对伴营养不良的患儿补锌后可增加其体重。结论：迁延性腹泻患儿体内锌水平降低,补锌可提高其临床治愈率及缩短疗程。     

迁延性腹泻病患儿内镜特点及血清、结肠灌洗液中一氧化氮、丙二醛、超氧化物歧化酶水平变化的意义

目的 了解迁延性腹泻病结肠黏膜患儿的内镜下特点及血清和结肠灌洗液中一氧化氮(NO)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平变化及意义.方法 选择2009年3月- 2010年6月本科收治的迁延性腹泻病患儿115例(迁延性腹泻组).另选择同期住院的急性腹泻病患儿115例(急性腹泻组)及体检健康儿童115例(健康对照组)作为对照.对迁延性腹泻组患儿行结肠镜检查.3组患儿均采用硝酸还原酶法测定血清NO水平,硫代巴比妥法测定MDA水平,黄嘌呤氧化酶法测定SOD水平.结果 迁延性腹泻组患儿结肠镜下所见病变主要以左半结肠为主,其中43例结肠黏膜呈大小为1～2 mm疱疹样改变伴充血糜烂;52例患儿结肠黏膜糜烂水肿;12例结肠黏膜充血水肿,血管网模糊;8例未见明显异常.迁延性腹泻组结肠灌洗液中NO、MDA、SOD水平治疗前后比较差异均有统计学意义(u=10.32、6.57、4.00,Pa＜0.05).迁延性腹泻组和急性腹泻组血清NO、MDA水平比较差异均无统计学意义(u=0.85、0.78,Pa＞0.05),SOD水平比较差异有统计学意义(u=57.13,P＜0.01).健康对照组血清NO、MDA、SOD水平与迁延性腹泻组(u=12.07、10.53、17.70,Pa＜0.01)及急性腹泻组(u=14.70、9.79、7.33,Pa＜O.05)比较差异均有统计学意义.迁延性腹泻组治疗前后血清NO、MDA、SOD水平比较差异均有统计学意义(u =7.99、6.80、12.84,Pa＜0.05);急性腹泻组治疗前后血清NO、MDA、SOD水平比较差异均有统计学意义(u=11.31、6.95、8.59,Pa＜0.05).结论 NO生成所产生氧自由基及脂质过氧化反应在腹泻病的发病中发挥重要作用,并能导致结肠黏膜损害,而保护性因素(SOD)的持续降低则是腹泻病迁延不愈的重要因素.     

Clostridium difficile and its cytotoxin in hospitalized children with acute diarrhea.

A total of 498 children, aged 0-14 years, admitted at the B.C. Roy Memorial Hospital for Children, Calcutta, were investigated for the occurrence of Clostridium difficile and its cytotoxin. Of the children in the investigation, 369 suffered from acute diarrhea. Only 8.4% of these children had C. difficile in fecal samples and in vitro cytotoxin was demonstrated in 7%. In 27 (7.3%) of the patients with acute diarrhea C. difficile was isolated as the only pathogen. In contrast, among 129 control children not suffering from acute diarrhea, only 4 (3.1%) harboured C. difficile. Isolation of C. difficile was significantly higher in children under one year of age. None of these patients had any history of prior antibiotic therapy.     

Clostridium difficile in patients with cystic fibrosis

One hundred seven patients with cystic fibrosis (CF) and 54 other patients with risk factors for Clostridium difficile-associated disease were entered into a bacteriologic study to compare the rate of recovery of C difficile and cytotoxin in feces with occurrence of diarrhea and to investigate potentially protective or permissive relationships of fecal flora. Toxigenic C difficile was recovered from 22% of CF patients and 11% of patients with other diagnoses. Unlike the latter group, the majority (12/15) of CF patients who had cytotoxin recovered had formed stools and no history of diarrhea. Explanations for the lack of symptoms are speculative. Stool flora of CF patients was significantly more likely to include several bacteria with known inhibitory effects on C difficile. Recovery of C difficile and cytotoxin, however, was not associated with the decrease in rate of recovery or the mean bacterial count of any bacterium of fecal flora.     

Clostridium difficile-associated diarrhea in a pediatric hospital

This retrospective cohort analysis examined the risk factors, symptoms, and severity of disease associated with C. difficile in pediatric inpatients. Risk factors for a C. difficile-positive test were an oncologic diagnosis, diarrhea of more than 2 days' duration, and gastrointestinal symptoms, especially abdominal pain. Over a 3.5-year period, there was a total of 22 C. difficile-positive patients, and most had mild, self-limiting diarrheal illness. No cases of C. difficile diarrhea were identified. Seventy-eight percent of the C. difficile-positive patients were found to have alternate risk factors for diarrhea. Our data indicate that C. difficile rarely causes severe diarrhea in pediatric inpatients and that C. difficile testing should be limited to patients with severe prolonged diarrhea and abdominal pain.     

Relapsing pseudomembranous colitis

Pseudomembranous colitis secondary to C. difficile and its toxin(s) is a well-recognized disease in children and usually responds to treatment with oral vancomycin. There are well-documented reports of relapse in adults after initial successful treatment with vancomycin. This report documents relapse in a child who developed diarrhea following treatment of pseudomembranous colitis. Stool cultures were negative for C. difficile at the end of the initial course of treatment, but the organism was isolated from the stool when the diarrhea recurred. The symptoms improved following a second course of treatment with vancomycin and have not recurred during 8 months of follow-up monitoring.     

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??Antibiotic-associated diarrhea??AAD????which results from disturbance or destroying of balance in the gut microbiota caused by antibiotic therapy??is frequent pediatric complications. Clostridium difficile-associated diarrhea??CDAD?? is considered a severe colitis type of AAD. Antibiotics administration can result in gut microbiota alterations??i.e?? disturbance and redistribution in composition and significant drops in taxonomic diversity. Changes in the microbiota composition may lead to changes of host intestinal mucosal immune response pattern??being open to pathogen invasion binding sites??increased susceptibility to infection?? and induction of antibiotic resistant strains of colonization. Microbiota alterations cause decreased bacterial carbohydrate and disturbances of bile acid metabolism. The early intervention of probiotics can effectively reduce the incidence of AAD and CDAD. Clinical application of antibiotics and the use of probiotics at the same time are reasonable and effective.     

Etiology of diarrhea in pediatric outpatient settings

BACKGROUND: The frequency with which bacteria cause diarrhea evaluated in ambulatory settings is often unknown. We attempted to determine the microbiologic etiology of diarrhea in a private pediatric practice (site A) and a clinic serving largely immigrant children (site B) and to establish guidelines for bacterial culture. METHODS: Children with diarrhea were prospectively enrolled, and their stools were examined for diarrheagenic bacteria, viruses and parasites. RESULTS: A total of 123 and 103 children were enrolled at sites A and B, respectively. Stools from all (100%), 126 (55.8%), 104 (46.0%) and 75 (33.2%) were tested for bacterial enteric pathogens, parasites, Clostridium difficile toxin and viruses, respectively. Of the 75 patients whose stool underwent complete testing, 36 (48%) contained at least 1 definitive or plausible pathogen. Twelve stools (5.3%) tested positive for bacteria [Campylobacter jejuni (n = 7), Yersinia enterocolitica, Shigella flexneri, Shigella sonnei, Salmonella serogroup D and Salmonella Braenderup (n = 1 each)]. One contained Blastocystis hominis, 8 contained C. difficile toxin and 16 contained viruses (9 rotavirus, 5 adenovirus and 2 astrovirus). Visible fecal blood (P = 0.029), increased stool frequency (P = 0.035), abdominal tenderness (P = 0.011) and fecal white (P < 0.001) or red blood cells (P = 0.002) were associated with bacterial infection. All children with stool yielding diarrheagenic bacteria or C. difficile toxin had at least 1 of these factors, but so did 75% of children without these agents (positive predictive value, 11%; negative predictive value, 100%; sensitivity, 100%; specificity, 25%). CONCLUSIONS: The bacterial diarrhea prevalence is similar to that in other ambulatory studies, although the spectrum differs. Exclusion criteria for stool testing in diarrhea remain elusive. Studies to determine the etiology of unexplained diarrhea and cost-effective algorithms for diarrhea diagnosis, are needed.     

Metchnikoff and the centenary of probiotics: an update of their use in gastroenteric pathology during the age of development

Acute gastroenteritis, antibiotic-associated diarrhea, diarrhea due to Clostridium difficile and traveller's diarrhea, Helicobacter pylori infection and intestinal inflammatory diseases are primitive and/or secondary pathological conditions that alter the intestinal mucosa and microbiota. For years researchers have searched for solutions to restore and rebalance normal transit and intestinal flora. Elia Metchnikoff was the first one to introduce oral bacteriotherapy, that uses very efficient microorganisms that prevent putrefaction and aging. Oral bacteriotherapy has now evolved in probiotics, whose helpful action to prevent and treat some gastroenteric pathologies is currently being studied.     

Clostridium difficile and diarrhea in infants in the first half-year of life]

In order to study a possible etiological relationship between Clostridium and diarrhea in children of the first half year of life and to characterize the colonization of the intestine with these bacteria, bacteriological investigations of feces were carried out in neonates and babies aged 1, 4 and 14 days and 1, 3 and 6 months. The development of the children and their health status were monitored under home conditions. It has been established that the colonization of the neonates' intestine with Clostridium including C. Difficile occurs within the early times (since the 4th day of life). Later the colonization with C. difficile becomes wavy in nature. Among 7 types of Clostridium isolated from the intestine of the children, C. difficile occurred most frequently (29.1%). The overwhelming majority of the strains of these bacteria produced toxin whose activity did no exceed 10(-1)-10(-2). The cytopathic effect was mostly demonstrable in 72 hours. No convincing evidence was obtained about the etiological importance of C. difficile in the development of diarrhea in the children placed under observation. It is likely that the latter one was due to the disturbance of intestinal biocenosis, that manifested by profound quantitative disorders (proliferation of the opportunistic aerobic flora, a dramatic reduction of the content of bifido- and lactic acid bacteria up to their complete absence). At the same time a great number of children carrying C. difficile attests to a potential development of specific diarrheas (under hospital conditions and during massive antibacterial therapy).     

Pseudomembranous colitis

OBJECTIVE: To alert about the pseudomembranous colitis in children, a consequence of the use of antibiotics. METHODS: This report is the result of the clinical follow-up of a patient with chronic diarrhea after the use of several antibiotics. The bibliography was obtained through Medline system. RESULTS: Case report of a girl two years and seven months old, previously healthy, with a clinical picture of chronic diarrhea with dysenteric characteristics after the use of antibiotics, associated with important weight lost and hypoproteinemia. The diagnosis of pseudomembranous was established clinically and was confirmed by colonoscopy and the presence of Clostridium difficile toxin A in the stools. CONCLUSIONS: It is necessary to consider the C. difficile infection in any child with diarrhea associated to the use of antibiotics. The antibiotics in pediatric patients should always be prescribed with caution and precise indications.