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.

基于虚、毒、湿论治老年抗生素相关性腹泻

结合老年人的体质特点,对老年抗生素相关性腹泻(AAD)的病因病机及治法进行理论探讨。认为脾肾阳虚是老年AAD的根本内因,为发病之本,而药毒、水湿则是重要病邪,为致病之标。基于"虚、毒、湿"致病说,采用健脾温阳、化湿解毒之法,可扶正祛邪、标本兼治,方用肉蔻四神丸、四君子汤,常用药物有肉桂、干姜、茯苓、白术等。

基于脑肠轴的四神丸治疗老年功能性腹泻的作用及机制研究

目的 通过实验观察分析四神丸对老年功能性腹泻大鼠脑肠轴中5-羟色胺(5-HT)、P物质(SP)、谷胱甘肽过氧化物酶(GSH-Px)含量的影响。方法 SPF级12月龄雄性SD大鼠40只,体重(380±20)g,根据随机数字表法将其分为空白组、模型组、阳性药组、四神丸组,每组10只。大鼠采用注射氢化可的松(25 mg/kg)和灌胃番泻叶(0.45 g/ml)造模,记录大鼠体重、体温、腹泻指数和尿D-木糖排泄率。给药期,四神丸组和阳性药组分别服用四神丸混悬液0.183 g/ml和匹维溴铵混悬液1.523 mg/ml,空白组、模型组给予等体积生理盐水。连续给药14 d。观察各组下丘脑、结肠组织中5-HT、SP、GSH-Px含量的变化。结果 四神丸组于造模第2周因操作不当死亡1只,模型组于造模第4周因胃寒死亡1只,模型组与四神丸组各9只大鼠。给药前后,与空白组比较,模型组体重、体温降低,腹泻指数升高,尿D-木糖排泄率降低,差异有高度统计学意义(P<0.01)。给药后,与模型组比较,四神丸组体重、体温升高,腹泻指数降低,尿D-木糖排泄率上升,差异有高度统计学意义(P<0.01);与空白组比较,模型组5-HT、SP含量升高,GSH-Px含量降低,差异有高度统计学意义(P<0.01);与模型组比较,四神丸组5-HT、SP含量降低,GSH-Px含量升高,差异有高度统计学意义(P<0.01)。结论 四神丸能有效治疗脾肾阳虚型老年功能性腹泻,其机制可能参与调节脑肠轴中5-HT、SP、GSH-Px等脑肠肽的含量及表达有关。

老年重症细菌性肺炎患者抗生素相关性腹泻的临床特征与治疗策略研究

目的研究老年重症细菌性肺炎患者抗生素相关性腹泻的临床特征与治疗策略。方法方便选择使用抗生素后引起相关性腹泻的老年重症细菌性肺炎患者40例作为研究对象,收取时间在2018年1月-2019年1月,随机分两组,其中观察组实施益生菌制剂治疗;对照组实施常规治疗,分析两组治疗效果、不同时间段菌群及相关性腹泻、营养情况和住院时间。结果观察组老年患者治疗总有效率95.00%高于对照组,差异有统计学意义(χ~2=4.329,P<0.05)。治疗后15 d,观察组老年患者大肠杆菌数量、乳酸菌、双岐杆菌数量均低于对照组,差异有统计学意义(t=3.414,5.117,3.186,P<0.05)。观察组老年患者出现腹泻时间(7.12±1.02)d长于对照组出现腹泻时间、腹泻持续时间短于对照组,差异有统计学意义(P<0.05)。观察组老年患者白蛋白水平、总蛋白水平、住院时间短于对照组,差异有统计学意义(P<0.05)。结论在使用抗生素后引起相关性腹泻的老年重症细菌性肺炎患者中,肠道内有益菌均伴有不同程度减少,通过应用益生菌制剂治疗,纠正肠道菌群失调,对治疗抗生素相关性腹泻具有显著效果。

肠宁汤治疗老年抗生素相关性腹泻的临床研究

目的:观察肠宁汤对老年性抗生素相关性腹泻脾肾阳虚证的临床疗效。方法:将老年人抗生素相关性腹泻患者60例随机分为两组各30例。治疗组给予肠宁汤治疗,对照组给予培菲康。1周为1疗程,治疗2个疗程,观察疗效及治疗前后临床症状积分参数的变化。结果:治疗组总有效率为86.67%(95%CI=63.7%～97.7%),对照组为73.33%(95%CI=48.4%～90.7%);两组综合疗效比较(u=1.953 4,P=0.050 8);治疗后,治疗组临床症状总积分参数优于对照组亦处于临界状态(u=1.755 4,P=0.079 2)。结论:肠宁汤治疗老年性抗生素相关性腹泻的疗效优于培菲康的证据尚不充分,OR=0.42(95%CI=0.11～1.60),NNT=8(95%CI=3.0～22.0)。提示,肠宁汤治疗老年性抗生素相关性腹泻脾肾阳虚证具有可喜的研究前景。

老年重症细菌性肺炎患者抗生素相关性腹泻的临床特征与治疗策略

目的探讨老年重症细菌性肺炎患者抗生素相关性腹泻(AAD)的临床特征和相关因素,并进一步研究AAD的防治措施。方法对使用抗菌药物治疗后发生AAD的老年重症细菌性肺炎患者的治疗情况进行回顾性分析。结果老年重症细菌性肺炎患者572例中发生AAD患者有114例,发生率19.93%;其中AAD患者中≥80岁占62.28%(n=114)。发生AAD患者曾使用抗菌药物的品种及频率排序为第三代头孢菌素(37.3%)、加酶抑制剂青霉素类(28.6%)、碳青霉烯类(19.2%)、第二代头孢菌素(14.9%)。结论老年重症细菌性肺炎患者发生AAD的高危因素包括:患者高龄、基础疾病严重程度、使用抗菌药物时间、联合用药品种、疾病严重程度(APACHEⅡ)、是否有侵袭性操作。在临床上,合理选择和使用抗菌药物是预防控制老年危重症患者AAD发生的关键。药学监护能更好地帮助优化临床治疗方案,控制减少抗生素相关不良反应。

加味当归芍药汤治疗老年性感染性腹泻的疗效评价

目的:评价加味当归芍药汤治疗老年性感染性腹泻的有效性和安全性。方法:将临床收集的年龄56～82岁确诊为感染性腹泻的老年患者56例随机分为两组,观察组30例用中药加味当归芍药汤治疗,每日1剂,早晚温服。对照组26例口服甲磺酸左氧氟沙星(利复星北京双鹤药业)0.2 g,2次/d,比较两组患者的治疗效果与总不良反应发生率。结果:两组患者在临床症状、体征的缓解方面及病原菌的清除方面有显著差异,加味当归芍药汤组在前两项中优于抗生素利复星组。结论:加味当归芍药汤治疗老年性感染性腹泻安全、有效、无毒副作用,值得临床推广应用。

Clinical update for the diagnosis and treatment of Clostridium difficile infection

Clostridium difficile infection(CDI)presents a rapidly evolving challenge in the battle against hospitalacquired infections.Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests,such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production,which will soon revolutionize the diagnostic approach to CDI.New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents,while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI.Through a comprehensive review of current medical literature,this article aims to offer an intensive review of the current state of CDI diagnosis,discuss the strengths and limitations of available laboratory tests,compare both current and future treatments options and offer recommendations for best practice strategies.

俞募配穴温针灸法联合补中益气汤治疗老年性慢性腹泻的临床观察

目的:探讨俞募配穴温针灸法联合补中益气汤治疗老年性慢性腹泻的临床疗效。方法:选取2017年8月至2018年9月西宁市妇幼保健计划生育服务中心收治的老年性慢性腹泻患者88例作为研究对象,将所有入组患者随机分为观察组与对照组,每组44例,对照组给予双歧杆菌四联活菌片口服治疗,观察组在对照组治疗的基础上联合补中益气汤和俞募配穴温针灸治疗,2组患者以2周为1个疗程,连续进行2个疗程后进行疗效观察。观察治疗后2组临床症状改善情况及疗效,检测并比较治疗前后2组血清胃肠激素及脑肠肽水平。结果:与治疗前比较,治疗后2组晨起泄泻、腹部冷痛、腰膝酸软、食欲不振和形寒肢冷评分均显著下降(P<0.01),且观察组显著低于对照组(P<0.01)。治疗后4周观察组总有效率为93.18%,对照组为77.27%,观察组总有效率高于对照组(P<0.05)。治疗后2周、4周、3个月观察组气虚积分均显著低于对照组(P<0.05或P<0.01)。与治疗前比较,治疗后2组血清MOT、GAS、5-HT、SP水平均显著下降,血清VIP、CGRP水平均显著升高(P<0.05或P<0.01),且组间差异有统计学意义(P<0.05或P<0.01)。结论:俞募配穴温针灸法联合补中益气汤治疗老年性慢性腹泻可显著缓解临床症状,调控胃肠激素及脑肠肽水平,治疗效果确切。

肠溶阿司匹林治疗老年肠运动功能异常性腹泻的临床疗效

目的探讨肠溶阿司匹林治疗老年肠运动功能异常性腹泻的临床效果。方法将老年肠运动功能异常性腹泻患者500例随机分为对照组和观察组,每组250例;对照组给予整肠生治疗;观察组给予整肠生+肠溶阿司匹林治疗,比较两组的临床治疗效果。结果观察组患者在用药后2、5 d的治疗总有效率明显高于对照组(P<0.05),用药后7 d两组的治疗总有效率均为100.0%,差异无统计学意义(P>0.05)。观察组患者的排便次数恢复正常时间、大便性状恢复正常时间及肠鸣音恢复正常时间均明显短于对照组(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论应用肠溶阿司匹林治疗老年肠运动功能异常性腹泻效果显著,值得临床推广。

The Florajen Digestion Balance Patient Experience Study

Background: Antibiotics have long been associated with gastrointestinal (GI) side-effects, leading to antibiotic noncompliance, related morbidities and increased costs. Antibiotic-induced disruption of intestinal microbiota has created interest in prophylactic use of probiotics to prevent antibiotic-associated GI side-effects, with recent trials suggesting GI benefits with concomitant probiotic and antibiotic use. The aim of this study was to see if commercially available Florajen Digestion can help maintain GI health during antibiotic regimens in the community. Methods: This prescriber and pharmacist directed, open label, patient experience study took place between September 2018 and January 2019. Healthcare professionals (HCPs) and patients from 40 states participated. Florajen Digestion probiotic was given to patients free of charge through their prescriber or pharmacist when prescribed or dispensed antibiotics. Surveys were completed by HCPs and patients, who reported on antibiotics prescribed/taken, GI upset, compliance and product satisfaction. Results: A total of 839 HCPs and 404 patients completed the study. Although 63% of patients reported prior GI side-effects with antibiotic use, only 12% experienced GI upset with concomitant Florajen Digestion use. Approximately 93% of patients completed their antibiotic regimen, with 77% asserting that Florajen Digestion helped them complete their course of antibiotics and 88% extremely satisfied with the probiotic. Among HCPs, 94% believed reducing side-effects improved antibiotic compliance, with 88% stating that probiotics should be recommended concomitantly with oral antibiotics. Conclusion: The results reveal the GI benefits of concomitant use of Florajen Digestion probiotics with antibiotics and support recommendation of Florajen Digestion by HCPs when prescribing or dispensing antibiotics.

综合护理干预在老年腹泻大小便失禁患者会阴护理中的应用

目的研究综合护理干预方法对于老年腹泻大小便失禁患者会阴部位护理的影响和作用。方法随机抽取2017年5月至2019年4月在我院就诊的192例老年腹泻患者,将这些患者按照随机数字表法分为观察组和对照组,各有患者96例,观察组使用综合护理干预的方法,对照组使用常规的护理干预方法,比较两组患者的1 d排便次数和肛周保持干燥时间。结果观察组1 d的排便次数在5次以下者为82例,对照组1 d的排便次数在5次以下的为50例,两组1 d的排便次数比较差异有统计学意义(P<0.05)。观察组中能够保持12 h以上的干燥环境的有84例,对照组中保持干燥时间在12 h以上的58例。两组肛周保持干燥时间经统计学比较差异有统计学意义(P<0.01)。结论综合护理干预可以有效减少并发症的发生概率,患者的满意度比较高,生理情况和心理情况都有明显改善。

王道坤教授温中止泻汤治疗老年顽固性腹泻经验

当下老年顽固性腹泻发病率较高,西医多采用对症治疗,但部分患者治疗效果常不理想。中医药辨治老年顽固性腹泻具有显著优势和确切疗效,首届甘肃省名中医王道坤教授认为老年顽固性腹泻治疗要重视老年人的脾肾阳虚体质特点并进行综合论治。此文总结了王道坤教授治疗老年顽固性腹泻的临证经验,以期为同道治疗老年顽固性腹泻提供更多诊疗思路。

基于“虚、毒、湿”理论培元理肠方治疗老年抗生素相关性腹泻的临床研究

目的:基于"虚、毒、湿"理论,探讨培元理肠方治疗老年抗生素相关性腹泻的临床疗效。方法:选取我院抗生素相关性腹泻老年患者90例,采用随机分组软件(Rand A1.0)分为3组,即试验组、对照Ⅰ组、对照Ⅱ组,每组30例。试验组给予培元理肠方治疗,对照组分别给予培菲康、固肠止泻丸治疗,观察评价治疗前后临床症状积分的变化。结果:试验组总有效率90.00%(95%CI=74.15%~97.90%),对照Ⅰ组总有效率76.67%(95%CI=61.54%~91.80%),对照Ⅱ组总有效率80.00%(95%CI=65.69%~94.31%),3组综合疗效比较(χ~2=3.299 7,P>0.05),差异无显著性意义;试验组总积分下降显著低于对照I组(t=-2.948 7,P<0.01)、对照Ⅱ组(t=3.169 3,P<0.01)。结论:采用培元理肠方治疗AAD的疗效可能优于对照Ⅰ组,其收益为OR=0.37(95%CI=0.08~1.57),NNT=8(95%CI=3.11~25.59)。

郑启仲教授苓桂术甘汤临证应用经验

苓桂术甘汤出自《伤寒论》,主要治疗痰饮相关疾病。郑启仲教授在临床上广泛应用,取得了良好的临床疗效,包括老年性慢性支气管炎、慢性胃潴留、多发性抽动症和慢性腹泻等。文章择数例典型病例阐述郑启仲老师应用苓桂术甘汤的运用经验和理论探讨,以飨同道。

俞募配穴温针灸法治疗脾胃虚弱证老年性慢性腹泻临床疗效观察

[目的]:观察使用俞募配穴温针灸法治疗脾胃虚弱型老年性慢性腹泻的临床疗效。[方法]将59例脾胃虚弱证老年性慢性腹泻的患者,随机分为2组。治疗组采用俞募配穴温针灸法,对照组口服双歧杆菌三联活菌胶囊,治疗8周后观察比较2组的临床疗效。[结果]治疗8周后,在临床总有效率方面,治疗组(93.33%)高于对照组(82.76%),差异有统计学意义(P<0.05)。[结论]俞募配穴温针灸法治疗脾胃虚弱型老年性慢性腹泻的疗效较对照组口服双歧杆菌三联活菌胶囊更佳,并且能有效减少大便频率,改善大便性状,缓解腹胀、腹痛等相关伴随症状,升高血清抑胃肽含量。