Clostridium Difficile In Children Research Articles

Infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease

Objective: To explore the infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease (IBD). Methods: From July 2015 to October 2016, the fecal samples and clinical data of 30 IBD children admitted to Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, as well as the specimens and data of 30 healthy children were collected in the meantime. The toxin gene of Clostridium difficile was detected and clinical characteristics of children with positive toxin gene were analyzed retrospectively. χ(2) test was used to compare the variables between groups. Results: Among the 30 IBD patients, 15 were in ulcerative colitis (UC) group and 15 in Crohn's disease (CD) group. In the IBD group, 6 (3 in UC and 3 in CD group) had positive result of toxigenic Clostridium difficile (20%), among whom 5 were toxin Clostridium difficile A (tcdA) +toxin Clostridium difficile B (tcdB) -, and 1 was tcdA+tcdB+. In the healthy group, only one had positive result of toxigenic Clostridium difficile (3%), which was tcdA+tcdB-. Binary toxin gene was negative in both groups. The infection rate of toxigenic Clostridium difficile in IBD group was significantly higher than that in healthy control group (χ(2)=4.043, P=0.044). In UC group, no Clostridium difficile toxin gene was detected during the remission period (0/1), one case was positive for toxin gene (1/11) during mild active period, and 2 cases were (2/3) during moderately active period. There were significant differences in the infection rate of toxigenic Clostridium difficile between patients in different active period (χ(2)=4.000, P=0.046). The main manifestations of the 6 cases were diarrhea, abdominal pain and bloody stool, and the relapsed case was characterized by sudden aggravation. TcdA was detected in all toxin gene positive samples, and 1 case combined with tcdB had more serious bloody mucopurulent stool. Five cases had colonoscopy, but there was no obvious characteristics of toxigenic Clostridium difficile colitis such as yellow white plaques or pseudomembranous spot. Three cases had antibiotic exposure history. All 6 cases were sensitive to metronidazole treatment, and stable without relapse during the 3-month follow-up. Conclusions: The infection rate of toxigenic Clostridium difficile in children with IBD is higher than that in healthy children. The patients with both tcdA and tcdB could have more serious clinical symptoms, although there may not be specific pathological changes of toxigenic Clostridium difficile colitis. The recognition of toxigenic Clostridium difficile infection in IBD children should be strengthened in clinical work.

Molecular characteristics of Clostridium difficile in children with acute gastroenteritis from Zhejiang

BackgroundClostridium difficile infection (CDI) has an increasing pediatric prevalence worldwide. However, molecular characteristics of C. difficile in Chinese children with acute gastroenteritis have not been reported.MethodsA five-year cross-sectional study was conducted in a tertiary children’s hospital in Zhejiang. Consecutive stool specimens from outpatient children with acute gastroenteritis were cultured for C. difficile, and isolates then were analyzed for toxin genes, multi-locus sequence type and antimicrobial resistance. Diarrhea-related viruses were detected, and demographic data were collected.ResultsA total of 115 CDI cases (14.3%), and 69 co-infected cases with both viruses and toxigenic C. difficile, were found in the 804 stool samples. The 186 C. difficile isolates included 6 of toxin A-positive/toxin B-positive/binary toxin-positive (A+B+CDT+), 139 of A+B+CDT−, 3 of A−B+CDT+, 36 of A−B+CDT− and 2 of A−B−CDT−. Sequence types 26 (17.7%), 35 (11.3%), 39 (12.4%), 54 (16.7%), and 152 (11.3%) were major genotypes with significant differences among different antimicrobial resistances (Fisher's exact test, P < 0.001). The A−B+ isolates had significantly higher resistance, compared to erythromycin, rifampin, moxifloxacin, and gatifloxacin, than that of the A+B+ (χ2 = 7.78 to 29.26, P < 0.01). The positive CDI rate in infants (16.2%) was significantly higher than that of children over 1 year old (10.8%) (χ2 = 4.39, P = 0.036).ConclusionsCDI has been revealed as a major cause of acute gastroenteritis in children with various genotypes. The role of toxigenic C. difficile and risk factors of CDI should be emphatically considered in subsequent diarrhea surveillance in children from China.

P080 A 5-year retrospective study on the role of Clostridium difficile in children with prolonged or muco-hematic diarrhea

P080 A 5-year retrospective study on the role of Clostridium difficile in children with prolonged or muco-hematic diarrhea

An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive

To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI). Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube. A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative. A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.

Evaluation of Nested Polymerase Chain Reaction and Immunoassay for Rapid Diagnosis of Clostridium difficile in Children with Community Acquired Diarrhea

Clostridium difficile (C. difficile) is a known pathogen associated with diarrhea especially in hospital acquired diarrhea. Yet, it is being recognized as a probable etiology for community acquired diarrhea. The aim of the present study was to detect the presence of C. difficile as a pathogen causing community acquired diarrhea in children and to verify the value of different laboratory methods for diagnosis, namely specific culture, immunoassay for toxin detection, and nested polymerase chain reaction (nested-PCR). This prospective study was carried out in children attending Mansoura University Children's hospital complaining of acute diarrhea between the periods from January 2015 until December 2015. Stool samples were collected and subjected to microbiological culture specific for C. difficile and rapid detection of toxin A by chromatographic device and by nested PCR for toxin B detection. Stool samples were collected from 413 children. C. difficile was isolated by culture from 41 patients (9.9%), while direct nested-PCR detected 39 (9.4%) toxigenic strains. Toxin A was detected in all 41 positive culture samples (9.9%). In comparing the clinical and laboratory findings between patients with C. difficile and those without C. difficile, though there was a higher association of bloody, watery diarrhea in patients with C. difficile these associations were not statistically significant (p = 0.4, p = 0.5, respectively). Comparing nested-PCR and toxin detection with culture for detection of C. difficile showed an excellent accuracy of both methods. From this study, we can conclude that community acquired diarrhea due to C. difficile is common among children. It should be sought among the pathogens causing this infection. Rapid laboratory detection of toxin A by a rapid chromatography device is accurate compared to time consuming culture. Moreover, nested PCR for toxin B is an accurate and rapid method when it is available.

Clostridium Difficile in Children- A Multifaceted Infection

Two case reports of children with muco-hemorrhagic diarrhea positive for Clostridium difficile introduce into the world of Clostridium difficile infection in the pediatric age. Epidemiological, clinical, and microbiological findings represent pieces of the puzzle of one of the most emerging infections at all the ages.

The impact of Clostridium difficile on paediatric surgical practice: a systematic review.

The pathogenic potential of Clostridium difficile in children remains a controversial subject as healthy infants can be colonised by this organism. However recent analyses have clarified that C. difficile is an important enteropath in paediatric populations, particularly in antibiotic-associated diarrhoea. Paediatric surgical patients including those with Hirschsprung's disease (HD) may be especially vulnerable to C. difficile infection (CDI) and complicated C. difficile enterocolitis such as pseudomembranous colitis may require surgical management if refractory to medical therapy. Reports of increasing prevalence and emergence of hyper-virulent strains of C. difficile worldwide prompted an examination of the literature to assess the impact of CDI on current paediatric surgical practise. The literature was searched using a combination of the MESH terms "hirschsprung's disease", "enterocolitis", "clostridium difficile", and "children". Cases of Hirschsprung's associated enterocolitis (HAEC) investigated for C. difficile and complicated CDI in non HD patients were identified and analysed for clinical parameters, diagnostic evaluations, surgical interventions and outcome. Pathogen isolation in HAEC was infrequently described. Only 98 children have been reported with C. difficile during an episode of HAEC over the last 40 years and aetiology remains unclear as asymptomatic carriage of C. difficile in HD occurs. Nonetheless 34 confirmed cases of pseudomembranous colitis complicating HD are reported in the literature with an associated 50 % mortality rate. Over 20 % of non Hirschsprung's patients with reported severe or complicated CDI required operative intervention. The need for surgery was associated with the presence of co-morbidity and high mortality occurred in this group. Severe or complicated CDI in both HD and non HD paediatric patients is associated with high mortality and often requires surgical intervention. Although these patient cohorts represent a small number of cases, CDI should be suspected in children presenting with enterocolitis to enable early diagnosis and timely surgical intervention, particularly in patients with co-morbid conditions or preceding antibiotic use.

Concurrent Infections of Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile in Children during a Cryptosporidiosis Outbreak in a Pediatric Hospital in China

BackgroundOver 200 cryptosporidiosis outbreaks have been reported, but little is known if other enteric pathogens were also involved in some of these outbreaks. Recently, an outbreak of cryptosporidiosis linked to poor hygiene by two Cryptosporidium hominis subtypes occurred in a pediatric hospital ward (Ward A) in China, lasting for more than 14 months. In this study, the concurrence during the outbreak of three other enteric pathogens with a similar transmission route, Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile, was assessed.Methods/Principal FindingsThe occurrence of G. duodenalis, E. bieneusi, and C. difficile in 78 inpatients from Ward A and 283 and 216 inpatients from two control wards (Wards C and D) in the same hospital was examined using molecular diagnostic tools. Significantly higher infection rates were found in children in Ward A for all study pathogens than in Wards C and D (P<0.01): 9.5% versus 1.4% and 0% for G. duodenalis, 10.8% versus 2.8% and 3.7% for E. bieneusi, and 60.8% versus 37.8% and 27.8% for C. difficile, respectively. These differences were mostly seen in children ≤12 months. Enteric pathogen-positive children in Ward A (31/58 or 53.4%) were more likely to have mixed infections than those in Ward C (4/119 or 3.4%) or D (5/68, 7.4%; P<0.01). Having cryptosporidiosis was a risk factor for G. duodenalis (OR = 4.3; P = 0.08), E. bieneusi (OR = 3.1; P = 0.04), and C. difficile (OR = 4.7; P<0.01) infection. In addition, a lower diversity of G. duodenalis, E. bieneusi, and C. difficile genotypes/subtypes was observed in Ward A.Conclusions/SignificanceData from this study suggest that multiple pathogens were concurrently present during the previous cryptosporidiosis outbreak. Examination of multiple enteric pathogens should be conducted when poor hygiene is the likely cause of outbreaks of diarrhea.

Editorial Commentary: Clostridium difficile in Children: Colonization and Consequences

The incidence of Clostridium difficile infection (CDI) has dramatically increased in the past decade. In some parts of the United States, CDI now surpasses methicillin-resistant Staphylococcus aureus as the most common healthcare-associated infection [1]. CDI also appears to be causing increasingly severe illnesses and more deaths, and exerting a growing burden on healthcare systems [2–6]. The preponderance of literature on this problem has been derived from adult clinical and epidemiologic studies. Clostridium difficile was first described in the stools of neonates in 1935, and termed Bacillus difficilis “because of the unusual difficulty . . . encountered in its isolation and study” [7]. Although Hall and O’toole found that strains from infant stools were virulent when inoculated into guinea pigs and rabbits [7], C. difficile was not generally considered to be a human pathogen until 4 decades later, when Bartlett et al linked these bacteria to antibioticassociated pseudomembranous colitis [8]. Now, nearly 4 more decades after that seminal association, emerging data suggest we need to focus on the biology of C. difficile in children. Sammons et al [9], in the current issue of Clinical Infectious Diseases, highlight the importance of C. difficile as a pediatric pathogen. They report a large multicenter retrospective analysis of morbidity and mortality associated with CDI in children. Children who develop symptomatic C. difficile diarrhea after admission to the hospital have a 6-fold greater risk of dying during that hospitalization than do controls with similar underlying disease and risk factors. In addition, children with CDI have significantly longer hospital stays and incur more costs than matched controls. These results are generalizable to the greater US population because the large dataset was obtained from children’s hospitals around the country. The study by Sammons et al [9] has additional strengths: They performed rigorous propensity score matching that took into consideration not only demographic data but also risk factors that would impact disease severity. The authors therefore minimized the bias that is inherent to studies of C. difficile in pediatrics, because children with significant comorbidities are at higher risk of acquiring C. difficile, and it might be difficult to attribute causality to C. difficile in these settings. They complemented this thorough evaluation with a sensitivity analysis that fortified their results. Their study had several limitations (as they acknowledge), such as using the third day of hospitalization as a cutoff to distinguish community-onset from hospital-onset disease, and the potential inaccuracy of information obtained from an administrative dataset. Taken together, the data reported by Sammons et al compel us to end our complacency about childhood CDI. It is understandable why we have discounted the importance of CDI in childhood. Multiple studies demonstrate that healthy infants often excreteC. difficile [10– 24], so attribution of pathogenicity in childhood cannot be claimed with conviction when a child with diarrhea has a positive C. difficile assay. Indeed, in a recent Seattle study, the frequency of C. difficile carriage was higher in controls than cases in children younger than 2 years [25]. Nonetheless, multiple reports over the past decade serve as preludes for the article by Sammons et al: Hospital diagnoses of pediatric C. difficile infection are increasing [26–30], and C. difficile infections are very common in children with inflammatory bowel diseases [31] and cancer [32]. Nylund et al [30] refuted the contention that C. difficile infections in Received 1 March 2013; accepted 4 March 2013; electronically published 26 March 2013. Correspondence: Phillip I. Tarr, MD, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8208, St Louis, MO 63110 (tarr@kids.wustl.edu). Clinical Infectious Diseases 2013;57(1):9–12 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cit160

Re-visiting Clostridium difficile in children: Reservoir, victims, both or none?

Re-visiting Clostridium difficile in children: Reservoir, victims, both or none?

Epidemiologic surveillance of Clostridium difficile diarrhea in a freestanding pediatric hospital and a pediatric hospital at a university medical center

To describe the epidemiology of Clostridium difficile in children, we cultured stool specimens from patients at the Children's Hospital Central California, Madera, CA (CHCC, n = 676) and at the University of California Davis Medical Center Pediatric Hospital, Sacramento, CA (UCDMC-PH, n = 301) for C. difficile, and toxins A and B genes and strain identity of the isolates were determined by polymerase chain reaction assays. A higher percentage of patients from UCDMC-PH were culture positive (148/301, 49%) and colonized with toxigenic strains (45/301, 15%) compared with CHCC (colonized = 178/676, 26%; toxigenic = 96/676, 14%, P ≤ .001). Multiple logistic regression analysis showed decreased colonization with inpatient status (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.46, 0.89; P = .007) and use of H-2 antagonists (OR = 0.55; 95% CI = 0.36, 0.84; P = .006), whereas underlying conditions (colonization: OR = 1.42; 95% CI = 1.02, 1.96; P = .04; toxin positive: OR = 1.60; 95% CI = 1.04, 2.44; P = .03) and exposure to ≥2 antiinfectives (colonization: OR = 1.56; 95% CI = 1.10, 2.20; P = .01; toxin positive: OR = 1.71; 95% CI = 1.10, 2.66; P = .02) increased colonization. Most isolates appear to be community acquired, although molecular analysis suggests some nosocomial transmission at UCDMC-PH. These data suggest that the epidemiology of colonization with C. difficile in children is different than previously reported.

Prevalence of Clostridium spp. and Clostridium difficile in children with acute diarrhea in São Paulo city, Brazil.

Species of Clostridium are widely distributed in the environment, inhabiting both human and animal gastrointestinal tracts. Clostridium difficile is an important pathogen associated with outbreaks of pseudomembranous colitis and other intestinal disorders, such as diarrhea. In this study, the prevalence of Clostridium spp. and C. difficile, from hospitalized children with acute diarrhea, was examined. These children were admitted to 3 different hospitals for over 12 months. Eighteen (20%) and 19 (21%) stool specimens from children with (90) and without (91) diarrhea respectively, were positive to clostridia. Only 10 C. difficile strains were detected in 5.5% of the stool samples of children with diarrhea. None healthy children (without diarrhea) harbored C. difficile. From these 10 C. difficile, 9 were considered as toxigenic and genotyped as tcdA+/tcdB+ or tcdA-/tcdB+, and 1 strain as nontoxigenic (tcdA-/tdcB-). They were detected by the citotoxicity on VERO cells and by the multiplex-polymerase chain reaction. Thirty clinical fecal extracts produced minor alterations on VERO cells. The presence of C. difficile as a probable agent of acute diarrhea is suggested in several countries, but in this study, the presence of these organisms was not significant. More studies will be necessary to evaluate the role of clostridia or C. difficile in diarrhoeal processes in children.

Pediatric Clostridium difficile: a phantom menace or clinical reality?

Clostridium difficile is the leading cause of nosocomial gastrointestinal illness in adult patients in hospitals. Even though C. difficile disease in adults has been well studied, research on pediatric C. difficile disease is still in its infancy. For many years it has been believed that C. difficile was a disease that affected only adults and was not a problem for children. This erroneous belief arose from the observation that neonates acquire C. difficile quickly (within 48 hours of birth) but show no intestinal symptoms (1–4). More recent evidence has been documented in case reports of pediatric C. difficile and outbreaks of C. difficile disease in pediatric populations (5– 7). Pediatric C. difficile disease has also been associated with the occurrence of severe complications and high mortality rates (8–10). The cascade of events in the pathogenesis of C. difficile disease is similar in children and adults. Normal intestinal microflora are disrupted by antibiotic exposure, medications, or surgery. If the child is then exposed to C. difficile (or its spores), colonization may occur, with production of toxins A and B. These toxins act on enterocytes, causing an inflammatory response and morphologic changes that lead to diarrhea or colitis. Host factors (age, diet, immune response) play an important role in determining whether C. difficile develops into asymptomatic carriage or active disease. Treatment for pediatric C. difficile disease usually relies on metronidazole or vancomycin, but clinical guidelines have not been defined for the pediatric population (11). As in adults, recurrent C. difficile disease that does not respond to conventional therapy develops in a proportion of children treated with antibiotic therapy.

Chronic diarrhea associated with Clostridium difficile in children.

Clostridium difficile toxin was associated with chronic diarrhea without classic symptoms of colitis in seven children (age range, 7 weeks to 7 years). All patients had received antibiotics. Six of the seven were treated with vancomycin hydrochloride and demonstrated improvement. After treatment, four patients suffered relapses, and three required further therapy. One patient had four relapses. During all clinical relapses, toxin reappeared in the stool; recovery was always associated with its disappearance. Fifty-six percent of family contacts examined had positive cultures. These findings document C difficile as a probable cause of chronic diarrhea in childhood and emphasize its infectious potential.