Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.

Probiotics for antibiotic-associated diarrhea:Do we have a verdict?

Probiotics use has increased tremendously over the past ten years.This was coupled with a surge of data relating their importance in clinical practice.Antibioticassociated diarrhea,whose frequency has risen recently,was one of the earliest targets with data published more than ten years ago.Unfortunately,available trials suffer from severe discrepancies associated with variability and heterogeneity of several factors.Most published randomized controlled trials and subsequent meta-analyses suggest benefit for probiotics in the prevention of antibiotic-associated diarrhea.The same seems to also apply when the data is examined for Clostridium difficile-associated colitis.However,the largest randomized double-blind placebo-controlled trial to date examining the use of a certain preparation of probiotics in antibiotic-associated diarrhea showed disappointing results,but it was flawed with several drawbacks.The commonest species of probiotics studied across most trials is Lactobacillus;however,other types have also shown similar benefit.Probiotics have enjoyed an impeccable safety reputation.Despite a few reports of severe infections sometimes leading to septicemia,most of the available trials confirm their harmless behavior and show similaradverse events compared to placebo.Since a consensus dictating its use is still lacking,it would be advisable at this point to suggest prophylactic use of probiotics to certain patients at risk for antibiotic-associated diarrhea or to those who suffered previous episodes.

Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A metaanalysis

AIM： To assess the effcacy and safety of probiotics for preventing pediatric： （1） antibiotic associated diarrhea and （2） Clostridium diffcile （C. diffcile） infections.METHODS： On June 3, 2013, we searched PubMed （1960-2013）, EMBASE （1974-2013）, Cochrane Da-tabase of Systematic Reviews （1990-2013）, CINAHL （1981-2013）, AMED （1985-2013）, and ISI Web of Science （2000-2013）. Additionally, we conducted an extensive grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroen-terology meetings, experts in the feld and correspondence with authors. The primary outcomes were the incidence of antibiotic-associated diarrhea （AAD） and C. difficile infections （CDI）. Dichotomous outcomes （e.g. , incidence of AAD or CDI） were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval （95%CI） and weighted on study quality. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain type, daily dose, quality of study and safety of probiotics. The overall quality of the evidence supporting each outcome was assessed using the grading of recommendations, assessment, development and evaluation criteria.RESULTS： A total of 1329 studies were identifed with 22 trials （23 treatment arms and 4155 participants） meeting eligibility requirements for our review of prevention of AAD and 5 trials （1211 participants） for the prevention of CDI. Trials in adult populations, trials of uncertain antibiotic exposure or studies which did not provide incidence of AAD were excluded. We found 12 trials testing a single strain of probiotic and 10 trials testing a mixture of probiotic strains. Probiotics （all strains combined） signifcantly reduced the incidence of pediatric AAD （pooled RR = 0.42, 95%CI： 0.33-0.53） and significantly reduced pediatric CDI （pooled RR = 0.35, 95%CI： 0.13-0.92）. Of the two strains with multiple trials, both signifcantly reduced pediatric AAD： Sac-charomyces boulardii lyo （pooled RR = 0.43, 95%CI： 0.32-0.60） and Lactobacillus rhamnosus GG （pooled RR = 0.36, 95%CI： 0.19-0.69）. There was no significant effect by type of antibiotic, or by duration or dose of probiotic. No adverse events associated were found in the 22 controlled trials relating to the use of probiotics.CONCLUSION： This meta-analysis found that probiotics signifcantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the effcacy varies signifcantly by the strain of the probiotic.

Efficacy of Xianglian pill for antibiotic-associated diarrhea: a protocol for systematic review and meta-analysis

Background:Antibiotic-associated diarrhea is a clinical common symptom of antibiotics overuse and occurs in 5%-70%of adults.Xianglian pill has been traditionally considered as an efficient treatment of diarrhea and gastrointestinal diseases for thousands of years.However,no systematic review and meta-analyses have focused on its positive effects.Hence,this protocol for systematic review and meta-analysis was developed to evaluate the effect and clinical safety of Xianglian pill on treating antibiotic-associated diarrhea.Methods:All randomized controlled trials published in Chinese and English and assessed use of Xianglian pill for antibiotic-associated diarrhea will be included.Databases of PubMed,EMBASE,Cochrane Library,China National Knowledge Infrastructure,Chinese Biomedical Literature,Wanfang,and Chinese Science and Technology Periodical Database will be searched for randomized controlled trials from their inception until November 16,2020.Primary outcomes will be the incidence of diarrhea and adverse events,and secondary outcomes will be bowel movements and microbiome characteristics.Two authors will extract data and assess the risk of bias independently.Risk ratio will be used to evaluate the results,and meta-analyses will be conducted using STATA 15.0 software.The review aims to demonstrate the effectiveness of Xianglian pill in the prevention and treatment of antibiotic-associated diarrhea.

Efficacy of a synbiotic chewable tablet in the prevention of antibiotic-associated diarrhea

Infection by Clostridium difficile, a complication of treatment with antibiotics, causes antibiotic- associated diarrhea (AAD) and can lead to colitis and pseudomembranous colitis. Incidence of C. difficile infection is increasing among the elderly undergoing antibiotics therapy confined to health care facilities, conditions that are expensive to treat, decrease the quality of life and are life threatening. Use of probiotics has been proposed as a method to decrease the incidence of AAD in health care facilities. To examine the efficacy of using probiotics, 120 nursing home residents undergoing antibiotic therapy were provided with a synbiotic tablet containing two probiotics, Saccharomyces boulardii and Bacillus coagulans, and a prebiotic, fructooligosaccharide. Residents were evaluated retrospectively for AAD and C. difficile infection. It was found that 95% of residents treated with antibiotics and taking the synbiotic tablet were free of AAD. More than 97% of the residents did not become infected with C. difficile. No adverse effects were reported. Minor side effects, gastrointestinal upset and nausea, were reported by less than 6% of the residents. The cause of the minor side effects was not known. Only 2.5% of the residents stopped taking the synbiotic tablet because of the gastrointestinal upset. These Results suggest that use of the synbiotic tablet prevents AAD and C. difficile infection in nursing home residents undergoing antibiotic therapy. It is concluded that this synbiotic tablet provides an easy to administer and safe approach to controlling AAD and C. difficile infection in residents in nursing homes.

北京地区抗生素相关性腹泻住院患者发生艰难梭菌相关性腹泻的影响因素分析

目的探讨北京地区抗生素相关性腹泻(antibiotic-associated diarrhea,AAD)住院患者艰难梭菌相关性腹泻(clostridium difficile associated diarrhea,CDAD)的现状及其影响因素。方法选取2022年7月至2023年7月北京9家医院近1年内就诊的AAD住院患者157例,将患者分为CDAD组(34例)和非CDAD组(123例)。采用多因素logistic回归方程分析北京AAD住院患者发生CDAD的影响因素。结果157患者中男79例,女78例,年龄18~94岁,平均(72.8±14.7)岁。CDAD发生率为21.7%(34/157),13例谷氨酸脱氢酶抗原检测结果阳性,毒素检测阴性,进一步行PCR检测和肠镜检查诊断CDAD,漏诊率为38.2%(13/34)。多因素logistic分析结果显示,BMI越小(OR=0.833,95%CI:0.733~0.947,P=0.005)、腹泻前抗生素使用天数越长(OR=1.065,95%CI:1.016~1.115,P=0.008)的患者更容易发生CDAD。结论北京地区AAD住院患者CDAD发生率为21.7%,单独依靠毒素检测漏诊率高达38.2%。BMI和腹泻前抗生素使用天数为AAD住院患者发生CDAD的独立风险因素,CDAD的临床表现更重。

抗生素相关菌群失调性腹泻的诊治规范

抗生素相关性腹泻（antibiotic—associated diarrhea，AAD）是指应用抗生素引起的腹泻，常与抗生素引起的肠道正常菌群失调有关，故又称抗生素相关菌群失调性腹泻。Bartlett将其定义为伴随着抗生素的使用而发生的无法用其他原因解释的腹泻。鉴于抗生素的应用现状，AAD的发生率可能有增加趋势，有报道约为5％-39％。

胃苓汤加减治疗脾虚湿滞型抗生素相关性腹泻临床研究

目的:观察胃苓汤加减治疗脾虚湿滞型抗生素相关性腹泻(AAD)的临床疗效。方法:将56例ICU收治的脾虚湿滞型AAD患者随机分为治疗组和对照组各28例。对照组采用双歧三联活菌胶囊及甲硝唑片治疗,治疗组采用胃苓汤加减治疗,2组均治疗7天。治疗后对比2组临床疗效,观察2组治疗前后血清白蛋白(Alb)、IgG及IgA水平的变化。结果:治疗组总有效率89.3%,对照组总有效率64.3%,2组比较,差异有统计学意义(P <0.05)。治疗前,2组血清Alb及IgG、IgA水平比较,差异均无统计学意义(P> 0.05)。治疗后,2组血清Alb及IgG、IgA水平均较治疗前升高,差异均有统计学意义(P <0.05);治疗组3项指标水平均高于对照组,差异均有统计学意义(P <0.05)。结论:胃苓汤加减治疗脾虚湿滞型AAD,能有效改善症状,提高患者的免疫力及Alb水平,值得临床借鉴。

FQ-PCR法分析葛根芩连汤对抗生素相关性腹泻模型肠道肠球菌数量的改变

为了检测葛根芩连汤在治疗抗生素相关性腹泻(AAD)时对模型肠道肠球菌的影响,试验采用氨苄西林灌胃巴马小型猪复制AAD模型,通过制备标准品DNA、构建标准曲线以建立检测肠球菌的FQ-PCR法,利用建立的FQ-PCR法检测对照组(3头)、模型组(3头)、葛根芩连汤7 d治疗组(3头)和葛根芩连汤14 d治疗组(3头)的十二指肠、空肠、回肠、盲肠和结肠内容物中肠球菌的数量。结果表明:通过标准曲线的构建得到肠球菌的标准曲线方程;与对照组相比,模型组肠道内肠球菌含量显著降低(P<0.05);与模型组相比,葛根芩连汤治疗组肠球菌在各个肠段中数量明显上升(P<0.05)。说明FQ-PCR法可以用于AAD模型治疗前后肠道肠球菌的数量检测。

防治抗生素相关性腹泻不可忽视血瘀证

目的:研究血瘀证对抗生素相关性腹泻(Antibiotic-Associated Diarrhea,AAD)发病率的影响及其在AAD证型分布中所占比例。方法:对2012年2月至2013年2月在我院ICU病房接受抗生素治疗的216例病例进行回顾性调查,研究血瘀证、非血瘀证患者接受抗生素治疗后AAD的发病率;血瘀证在AAD证型分布中所占的比例;引发AAD合并血瘀证的病理机制。结果:血瘀证患者接受抗生素治疗后AAD发病率45.26%>非血瘀证者31.67%,P<0.05;其中,脾气亏虚患者合并血瘀证者发生AAD几率58.33%>非血瘀证者12.50%,P<0.05;湿浊内阻患者合并血瘀证者发生AAD几率62.50%>非血瘀证者19.23%,P<0.05;脾虚湿浊患者合并血瘀证者发生AAD几率75.00%>非血瘀证者27.27%,P<0.05。在AAD证型分布中,血瘀证比例为29.63%,仅次于脾虚痰湿证64.20%居第二。在导致AAD合并血瘀证的病理机制中,痰饮瘀血互化占54.17%。结论:血瘀证、特别是脾虚湿阻型患者在合并血瘀证时更易发生AAD;血瘀证是AAD证型分布中的重要组成部分,其地位仅次于脾虚痰湿证;在多数情况下,导致AAD合并血瘀证的病理机制是痰饮瘀血互化。

双歧杆菌四联活菌片治疗儿童抗生素相关性腹泻的疗效及对患儿免疫功能的影响

目的观察双歧杆菌四联活菌片治疗儿童抗生素相关性腹泻(AAD)的疗效,并探讨其对患儿免疫功能的影响。方法选择2017年1月至2018年8月期间珠海市妇幼保健院小儿血液消化内科治疗的89例AAD患儿为研究对象,根据随机数表法分为观察组(n=44)和对照组(n=45),对照组予补液、思密达保护胃肠黏膜等常规治疗,观察组则在此基础上联合应用双歧杆菌四联活菌片治疗,疗程7 d。比较两组患儿的临床疗效、腹泻持续时间、病程时间等临床指标,并对其治疗前后的血清免疫球蛋白(IgA、IgM和IgG)的变化进行比较。结果观察组患儿的治疗总有效率为97.73%,明显高于对照组的84.44%,差异有统计学意义(P<0.05);观察组患儿的腹泻持续时间、病程时间分别为(2.98±0.92) d、(8.48±2.64) d,明显短于对照组的(3.67±1.15) d、(10.02±3.69) d,差异均有统计学意义(P<0.05);治疗后,观察组患儿的血IgA、IgG、IgM水平分别为(2.05±0.38) g/L、(11.52±3.13) g/L、(1.63±0.29) g/L,均明显高于对照组的(1.75±0.29) g/L、(9.57±2.26) g/L、(1.47±0.30) g/L,差异均有统计学意义(P<0.05)。结论双歧杆菌四联活菌片治疗儿童抗生素相关性腹泻可更有效地平衡肠道菌群,保护肠黏膜,从而提高患儿的免疫功能、缩短病程,提高临床疗效。

布拉氏酵母菌预防婴儿抗生素相关性腹泻临床分析

目的 :探讨布拉氏酵母菌对婴儿期肺炎患儿抗生素相关性腹泻的预防作用。方法:237例静脉应用抗生素的肺炎住院婴儿完全随机分为两组,预防组120例治疗开始即同时服用布拉氏酵母散;对照组117例,在出现腹泻后加用布拉氏酵母菌散;出现腹泻后两组均同时使用思密达散及适当补液。比较两组腹泻的发生率、疗效、腹泻持续时间并进行统计分析。结果:预防组出现腹泻21例,发病率为17.50%;对照组出现腹泻43例,发病率为36.75%。预防组患儿腹泻持续时间(3.14±1.24)d,较对照组时间(4.28±1.53)d短,差异有统计学意义(P<0.01)。预防组腹泻患儿总有效率为95.24%,较对照组69.77%高,差异有统计学意义(P=0.046)。结论:布拉氏酵母菌能有效预防婴儿肺炎患儿抗生素相关性腹泻的发生,并可缩短腹泻持续时间。

183例儿童抗生素相关性腹泻的临床分析

为了探讨儿童抗生素相关性腹泻（AAD）的危险因素,对2009~2010年因感染性疾病住院患儿中发生AAD的183例患儿临床相关资料进行统计分析,结果表明,婴幼儿、呼吸道感染、冬春季节、广谱联合抗生素应用为AAD的高发危险因素。

非食源性腹泻中产气荚膜梭菌的毒力型分布特征

目的探讨非食源性腹泻患者中分离的产气荚膜梭菌毒力型分布特征。方法选取2020年1月1日至12月31日清华大学附属北京清华长庚医院收治的非食源性腹泻住院患者粪便样本分离的86株产气荚膜梭菌,其中59株分离于抗生素相关性腹泻(antibiotic-associated diarrhea,AAD)患者,27株分离于非AAD患者。采用实时荧光聚合酶链反应(polymerase chain reaction,PCR)检测菌株的6种毒素基因,即产气荚膜梭菌alpha毒素(cpa)、beta毒素(cpb)、epsilon毒素(etx)、iota毒素(ι-iap)、肠毒素(cpe)和坏死性肠炎B毒素(netB),依据毒素类型将菌株分为A~G 7种毒力型,分析毒力型分布以及AAD组和非AAD组间毒力型的差异。结果86株产气荚膜梭菌中,毒素基因cpa、cpb、etx、ι-iap、cpe和netB的检出率分别为100.0%、5.8%、0.0%、0.0%、18.6%和2.3%;A~G毒力型分别占74.4%、0.0%、5.8%、0.0%、0.0%、17.4%和2.3%。A毒力型在AAD组和非AAD组的检出率分别为74.6%和74.1%,占比最高,其次是F毒力型,分别为13.6%和25.9%。AAD组与非AAD组A型、C型、F型和G型4种毒力型的检出率比较,差异无统计学意义(P=0.185)。结论非食源性腹泻患者感染的产气荚膜梭菌主要以A毒力型和F毒力型为主,在AAD中没有特征性毒力型,应同时检测alpha毒素和肠毒素,以避免漏诊。

儿科病房抗生素相关性腹泻危险因素分析

目的:分析患儿抗生素相关性腹泻(AAD)的临床特点,探讨不同患儿年龄、抗生素使用时间及抗生素种类对腹泻病的影响,并提出预防措施。方法:围绕抗生素应用与腹泻的关系,对我院儿科近3年来住院的抗生素相关性腹泻患儿进行临床分析,并采用SPSS12.0对数据进行分析。结果:1岁以内的婴儿使用抗生素、抗生素使用时间7d以上、联合应用二种以上抗生素的患儿AAD的发病率高于对照组(P均<0.05)。结论:感染性患儿不恰当使用抗生素是AAD的危险因素。

微生态制剂对新生儿抗生素相关性腹泻的预防作用

目的探讨微生态制剂枯草杆菌二联活菌颗粒对新生儿抗生素相关性腹泻（AAD）的预防作用。方法2007年1月～2011年1月患新生儿肺炎的住院新生儿120例分为预防组和对照组各60例，均予常规抗炎、对症、支持治疗，预防组在应用抗生素的同时予微生态制剂枯草杆菌二联活菌颗粒口服；比较两组出现抗生素相关性腹泻的例数及腹泻病程。结果预防组发生抗生素相关性腹泻5例（占8．3％），对照组发生抗生素相关性腹泻13例（占21．7％）。预防组腹泻病程（3．50±0．53）天，对照组（5．70±0．39）天。两组对比差异有显著性（P〈0．05）。预防组患儿均未观察到微生态制剂相关的不良反应。结论枯草杆菌二联活菌颗粒预防新生儿抗生素相关性腹泻安全有效。

抗生素相关性腹泻治疗现状评价

目的:对抗生素相关性腹泻的病因、机制、危险因素及诊治现状进行评价。方法:收集国内外相关文献进行整理归纳。结果及结论:抗生素相关性腹泻诱因主要为抗生素的应用,常由肠道正常菌群遭到破坏、胃肠蠕动加快、肠道黏膜损害等引发。一经确诊应立即停用相关抗生素,轻症患者停用后多能自愈,重症患者需用针对艰难梭菌的抗生素治疗。合理使用抗生素是预防AAD的关键。

某院儿科2010年抗生素相关腹泻临床分析

目的:提高对抗生素应用过程中导致婴幼儿抗生素相关腹泻的认识,并探讨其防治方法。方法:抽取应用抗生素治疗的全部住院病历,按抗生素相关腹泻的诊断标准,统计分析其发病率,探讨其发病原因,提出防治办法。结果:抗生素相关腹泻总发病率为10.8%,其中头孢呋辛占7.6%;头孢曲松占1.2%;克林霉素占0.8%;两联以上抗生素占1.3%。应用微生态制剂及肠黏膜保护剂,佐以免疫增强剂静脉用人血免疫球蛋白(IVIG),防治疗效满意。结论:儿科抗生素相关腹泻发病率较高,受多种因素影响,可用微生态制剂及免疫增强剂防治。