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 efficacy and safety of probiotics for preventing pediatric:(1) antibiotic associated diarrhea and(2) Clostridium difficile(C. difficile) infections.METHODS: On June 3, 2013, we searched Pub Med(1960-2013), EMBASE(1974-2013), Cochrane Database 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 gastroenterology meetings, experts in the field 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 identified 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) significantly 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 significantly reduced pediatric AAD: Saccharomyces 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 significantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the efficacy varies significantly 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.

Pharmaceutical care of a patient with antibiotic-associated encephalopathy

Objective:To provide reference of pharmaceutical care for the clinical treatment of a severe patient with antibiotic-associated encephalopathy.Methods:Clinical pharmacists participated in the clinical treatment of the patient with antibiotic-associated encephalopathy,provided pharmaceutical care for clinicians,including the evaluation of adverse drug events and the prevention of adverse drug interaction and development of anti-infection programs by using Pharmacokinetics/pharmacodynamics theory and therapeutic drug monitoring technique.Results:Through active clinical treatment and pharmaceutical care,the symptoms of patients with encephalopathy were relieved,and the infection was effectively controlled.Conclusion:Clinical pharmacists play a positive role in the treatment for the case with antibiotic associated encephalopathy.

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.

Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection

The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections(CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation(FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.

Atypical presentation of pseudomembranous colitis localized in adenomatous polyps

The most frequent cause of pseudomembranous colitis is Clostridium difficile(C.difficile) infection.This type of colitis is characterized by an endoscopic pattern of numerous small,yellowish or whitish plaques diffusely distributed,which typically compromises the rectum extending to proximal colon.Occasionally,the pseudomembranes compromise only the transverse or right colon,but their exclusive localization over polyps has not been reported.In this case report we have described a patient with symptoms compatible with C.difficile infection and positive for C.difficile toxigenic culture.Colonoscopy examination showed two small polyps with a whitish surface,and histopathological analysis confirmed them to be pseudomembranes over tubular adenomas.The rest of the colonic mucosa was normal and no other cause was demonstrated.We suggest that this particular distribution might be due to a higher affinity for dysplastic cells such as adenomatous polyps of colon by C.difficile and/or its toxins.

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.

Research Progress of Qiweibaizhu Powder in Treating Digestive System Diseases

Diarrhea is a common clinical problem that can lead to health complications,including death.It is the second-most common cause of death in children.The World Health Organization introduced a program to encourage the development and use of traditional herbal medicines in the treatment of diarrhea.Qiweibaizhu Powder(QWBZP)is a well-known pediatric prescription in China that is commonly used to treat digestive system diseases,such as diarrhea,which is also a type of syndrome in traditional Chinese medicine.Many studies have examined the clinical effects and mechanisms of QWBZP,and innovative and improved formulations have been developed.Recent studies on the effects of QWBZP on diarrhea caused by human rotavirus,antibiotic-associated diarrhea,and mesenteric lymphadenitis in experimental models and clinical trials with diarrhea patients have been reviewed.We conducted a literature search of several databases,including PubMed,China National Knowledge Infrastructure,Chongqing VIP Information Co.,Ltd.,and Wanfang.A short background of the QWBZP is also provided.The collective findings highlight the curative effects of QWBZP on diarrhea caused by viral infection,antibiotic use,and mesenteric lymphadenitis.Furthermore,QWBZP can regulate the balance of the gastrointestinal microbiota and protect and repair the intestinal mucosal barrier.This review will provide a reference for further studies on QWBZP.