Clostridium Difficile Infection In Children Research Articles

Antibiotic treatment of Clostridium difficile infection in children – a challenge in pediatric practice

Results Between January 1 2005 and July 31 2014, 52 patients were diagnosed with CDI. A large number of cases (61%) were diagnosed in the age group 1 to 4 years. The sex ratio was M/F = 0.9/1. 36% of patients had communityacquired CDI. In mild/moderate forms metronidazole was administered as a first-line treatment in 32 (61%) cases and proved efficient in 25/32 (78.1%) cases; vancomycin was used and was efficient in 18 cases. In severe forms (7.7%), the association of intravenous metronidazole and oral vancomycin was the option of choice and this approach cured all these cases. We report 11 patients with recurrent CDI (21%); in these cases oral vancomycin was efficient for the treatment of the recurrence. In 3 cases with a second recurrence rifaximin was the chosen therapy. Six out of 11 children with recurrent CDI had comorbidities (Hirschsprung disease, ulcerative colitis).

Fecal microbiota transplantation in the treatment of refractory Clostridium difficile infection in children: an update.

The use of transplanted fecal material for the treatment of diarrheal illness dates back to the fourth-century China. While fecal microbiota transplant has gained increasing popularity over the past 50 years for the treatment of refractory Clostridium difficile infections (RCDIs) in adults, it has only been recently utilized in children. The purpose of this article is to review the use of fecal microbiota transplant (FMT) in the treatment of pediatric RCDIs. Minimal pediatric data, including few case reports and series, document the successful use of FMT for treatment of RCDI in the past 2 years. Patients in these reports included otherwise healthy children, those with inflammatory bowel disease as well as significantly immunocompromised children. Donor fecal infusion via nasogastric tube, gastroscope or colonoscope in children aged 16 months and older demonstrated a high rate of symptom resolution and organism eradication. No complications to date have been reported in children who have undergone FMT. FMT is emerging as a well-tolerated and effective treatment for RCDI in not only adults but also children.

A hospital-based study of the clinical characteristics of Clostridium difficile infection in children.

Clostridium difficile infection (CDI) is an increasingly important cause of morbidity in hospitalized children. We describe the recent epidemiology of pediatric CDI at a children's hospital, compare community-associated (CA) and hospital-associated (HA) infections and identify risk factors for severe disease. Children with CDI at Texas Children's Hospital were identified from February 1, 2011, to October 31, 2011. Severe CDI was defined as the presence of a CDI-related complication or ≥2 clinical features: fever, bloody stools, leukocytosis, hypoalbuminemia or elevated creatinine. Standard epidemiologic definitions were used. One-hundred and nine unique patients 1-21 years of age with CDI were identified throughout the study period. The proportions of CA-CDI (41%) and HA-CDI (46%) were similar, whereas community-onset indeterminate CDI (13%) was less common. Children with malignancy or solid organ transplantation were more likely to have HA-CDI. Conversely, all children with inflammatory bowel disease had CA-CDI. Twenty-three patients (21%) met criteria for severe disease and 8 experienced a CDI-related complication, including 1 death attributable to CDI. On multivariate analysis, the presence of a gastrostomy tube (adjusted odds ratio: 3.09; 95% confidence interval: 1.07-8.94) and having community-onset indeterminate disease (adjusted odds ratio: 4.62; 95% confidence interval: 1.28-16.67) were found to be associated with severe CDI. A substantial proportion of pediatric CDI is CA and there are clinical differences between children with CA-CDI and HA-CDI. Children with CDI frequently experience severe disease, whereas complications are uncommon. Early identification and treatment of CDI should be pursued in children with gastrostomy tube and recent hospitalization.

Clostridium difficile infection in children: A pediatric experience

Clostridium difficile infection in children: A pediatric experience

Association of Clostridium difficile Infections with Acid Suppression Medications in Children

Multiple studies have confirmed associations between acid suppression medication and Clostridium difficile infections (CDIs) in adults. Therefore, we sought to evaluate an association between acid suppression medications and CDI in children. A retrospective self-controlled case series was performed utilizing billing records from the TRICARE Management Activity military health system database. Children ages 2-18 years from October 1, 2001 to July 31, 2013, who had an outpatient or inpatient record of CDI diagnosis were included. The relative incidences (RIs) of CDI or recurrent CDI were calculated comparing time periods prescribed and not prescribed proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). There were 2531 cases of CDI among 2437 patients, and 1190 (48.8%) were prescribed acid suppression medications. CDI were more likely to occur during periods when patients were prescribed a PPI (RI 2.36; 95% CI 2.22-2.52), H2RA (RI 1.95; 95% CI 1.63-2.34), or during periods while prescribed both simultaneously (RI 2.40; 95% CI 1.90-3.04). There were 265 (10.4%) cases that were classified as recurrent among 217 (8.9%) patients. Recurrent CDI also was found to be more likely during prescription periods of PPI (RI 1.74; 95% CI 1.51-2.00) and H2RA (RI 2.63; 95% CI 1.89-3.66). Acid suppression medications are associated with an increased risk of CDI and recurrent CDI. Judicious use of acid suppression medication should be considered, especially among those at highest risk for CDI.

Clostridium difficile Infection in Children with Inflammatory Bowel Disease: Current Evidence

Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. Questions about the role of infections in the development and exacerbations of inflammatory bowel disease remain unanswered. Among numerous bacteria that have been linked to IBD, the most frequently associated is Clostridium difficile. Clinical symptoms of C. difficile infection and an exacerbation of inflammatory bowel disease are often indistinguishable. In cases of diarrhea in patients with IBD and C. difficile infection, antibiotic treatment is recommended. This review attempts to summarize C. difficile infection's epidemiology and clinical features and describes current evidence on treatment of C. difficile infection in children with IBD.

The prediction of complicated Clostridium difficile infections in children.

We validated proposed definitions for severe Clostridium difficile infection (CDI) in adults for prediction of complicated CDI in children. Complicated CDI occurred in 9 of 202 cases. Definitions for severe CDI in adults showed poor measures for discrimination of complicated CDI in children, which calls into question the usefulness of such definitions in pediatric cohorts.

Predictors of First Recurrence of Clostridium difficile Infections in Children

Little is known regarding the risk of recurrence of Clostridium difficile infection (CDI) in children. In a 9-year cohort, 12% of hospitalized children with CDI had recurrent disease. Receipt of concomitant antibiotics and community-associated CDI were independently associated with recurrent disease in children hospitalized with CDI. Antibiotics administered for reasons other than treatment of CDI should be discontinued whenever possible.

Community-Associated Clostridium difficile Infections in Children

Community-Associated <i>Clostridium difficile</i> Infections in Children

Variation in Risk of Hospital-Onset Clostridium difficile Infection Across β-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia.

Antibiotic exposure is common among children with leukemia. However, limited data exist regarding the risk of Clostridium difficile infection (CDI) across anti-pseudomonal β-lactam antibiotics commonly used for fever and neutropenia. A multicenter cohort of children with newly diagnosed acute lymphoblastic leukemia (ALL) was established from 43 freestanding children's hospitals from 1999 to 2009. Patients were followed until their index CDI event, defined by the CDI ICD-9 code plus a C difficile test charge, or until 180 days from ALL diagnosis. Cox proportional hazards models were performed to identify the hazards of CDI after exposure to anti-pseudomonal β-lactams, adjusting for demographics, other antibiotic exposures, severity of illness, antacids, gastrointestinal manipulation, and confounding by hospital. A cohort of 8268 ALL patients was assembled; median age was 5.5 years (interquartile range, 3.26-10.58). Two-hundred sixty-eight (3.2%) patients developed CDI within 180 days of ALL diagnosis. Each 1-day increase in exposure to an anti-pseudomonal β-lactam within the prior 30 days was associated with a significantly increased risk for CDI (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01, 1.09). Ceftazidime (HR, 1.05; 95% CI, 1.02, 1.08) and cefepime (HR, 1.07; 95% CI, 1.02, 1.12) were each independently associated with CDI. Efforts to reduce total exposure to anti-pseudomonal β-lactam agents may help to reduce the risk of CDI in children with newly diagnosed ALL. Cefepime and ceftazidime were independently associated with CDI, whereas anti-pseudomonal penicillins and carbapenems were not. These findings, if confirmed, have potential implications for antibiotic choice during periods of fever and neutropenia.

Severe clinical outcome is uncommon in Clostridium difficile infection in children: a retrospective cohort study

BackgroundClostridium difficile infection (CDI) is the most common cause of health care–associated diarrhea in children and adults. Although serious complications of CDI have been reported to be increasing in adults, this trend has not yet been demonstrated in children. The purpose of this study was to examine the features of CDI in a pediatric population, with special attention to the occurrence of CDI-related severe outcomes.MethodsA chart review was conducted for patients with C. difficile infection detected by cytotoxin assay between August, 2008 and July, 2012. Basic demographics, mode of acquisition (nosocomial versus community), laboratory and clinical features, treatment, and outcome data were collected. Pulsed-field gel electrophoresis and polymerase chain reaction detection of toxin A (tcdA), toxin B (tcdB), binary toxin (cdtB) and tcdC genes were performed on isolates from nosocomial cases by the National Microbiology Laboratory, Winnipeg, Manitoba.ResultsNinety percent of children with CDI experienced resolution of symptoms by 30 days after disease onset and 2% experienced a severe outcome. There were no cases where colectomy was performed for CDI, and only one case where CDI contributed to death. Various combinations of clinical and laboratory features were not predictive of a severe outcome. Seventy-four percent of cases were nosocomial-associated. Among all cultured strains, the NAP4 strain occurred most frequently (24%), followed by NAP1 (11%). There was no association between strain type and clinical outcome; however, relapses were significantly more frequent in NAP4-infected children.ConclusionsSevere outcomes due to CDI are uncommon in children compared to adults. Further prospective pediatric studies on CDI in community and hospital settings are required to better understand risk factors, optimal treatment and the significance of NAP4 in pediatric CDI.

Clostridium difficile in the Pediatric Population of Monroe County, New York.

Clostridium difficile infection (CDI) incidence in hospitalized children has increased over the past decade and disease has been reported in the community. Therefore, population surveillance that includes nonhospitalized cases is important to accurately estimate the burden of CDI in children. We describe the epidemiology of CDI in the pediatric population of Monroe County, New York. Active, laboratory, and population-based surveillance for CDI has been ongoing in Monroe County through the Emerging Infections Program of the Centers for Disease Control and Prevention since 2010. Infants less than 12 months of age are excluded. In 2010, the incidence of CDI in the pediatric population was 33.8 per 100 000 population, which increased to 45.8 in 2011and remained stable in 2012. Seventy-one percent of the CDI cases were community-associated, 60% had an underlying medical condition, and 71% received antibiotics before their illness. The North American pulsed-field gel electrophoresis type 1 (NAP1) epidemic strain was identified in 27% of cultured stool specimens. Clostridium difficile infection has emerged as a disease affecting children in both the community and hospital settings, with a higher proportion of community illness in our population. The majority of children with CDI had chronic underlying conditions and prior antibiotic exposure. To prevent CDI in this population, the judicious use of antibiotics, especially in the outpatient setting, may be the best strategy. Further population-based studies are warranted to determine preventable risk factors for CDI in the pediatric population.

Clinical Characteristics of SymptomaticClostridium difficileInfection in Children: Conditions as Infection Risks and Whether Probiotics Is Effective

PurposeThis study investigated the clinical presentations of symptomatic Clostridium difficile infection (CDI) in children.MethodsWe reviewed the medical records of 43 children aged <20 years who showed either positive C. difficile culture or C. difficile toxin test results between June 2010 and April 2014.ResultsOf the 43 patients (mean age 6.7 years), 22 were boys. Sixteen patients (37.2%) showed both positive C. difficile culture and toxin test results. Seventeen out of 43 children (39.5%) had preexisting gastrointestinal diseases, and 26 children had other medical conditions that were risk factors for CDI. Twenty-eight children had a history of antibiotic treatment for >3 days, and the most frequently prescribed antibiotic was amoxicillin-clavulanate (35.7%). Twenty-eight patients were diagnosed with CDI despite taking probiotic supplements, most commonly Lactobacillus acidophilus (53.6%). The most common symptom was diarrhea (72.1%) at the time CDI was diagnosed. C. difficile was eradicated in 11 patients (25.6%) after treatment with oral metronidazole for 10-14 days, and in the two patients (4.6%) who required two courses of oral metronidazole. Sixteen patients (37.2%) showed clinical improvement without any treatment.ConclusionThis study showed the various clinical characteristics of CDI in children and that preexisting clinical conditions favored the development of CDI. In addition, CDI was found to occur in a number of patients even after probiotic prophylaxis given in conjunction with antibiotic therapy.

Clostridium difficile infection in children – clinical, diagnostic and therapeutic aspects

Background Clostridium difficile is the most common cause of antimicrobial-associated diarrhea and is a common healthcare associated pathogen. While asymptomatic carriage remains high among infants, recent epidemiological surveillance has demonstrated a rise in the prevalence of Clostridium difficile infection in children. Methods We present 4 cases of children admitted to the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” in the last year with Clostridium difficile colitis; the children had ages between 2 and 12 years. Diagnosis of infection was based on the presence of three or more stools in a 24 hour period, isolation of the organism and detection of toxins A/B in a diarrheal stool specimen (stool culture and PCR assay). We studied the clinical aspects and evolution after treatment. Results All children presented an important risk factor for Clostridium difficile infection: antimicrobial therapy prior to infection. Three children presented chronic pediatric comorbidities: one case of Ewing’s sarcoma; one case of gastroesophageal reflux disease, recent abdominal surgery for gastric volvulus, use of proton pump inhibitors; one case of milk protein allergy. The clinical signs and symptoms were: fever (3 cases), watery diarrhea (2 cases), bloody diarrhea (2 cases), cramping abdominal pain, vomiting, loss of appetite and malaise. The children received antimicrobial therapy: oral metronidazole in 2 cases, oral vancomycin in 2 cases, supportive treatment and probiotics, with good outcome. All patients recovered without complications. Relapse occurred in the case with osteosarcoma, after cytostatic treatment and he was treated with oral vancomycin. Rifaximin prophylaxis associated to the next cytostatic treatment prevented another relapse. Conclusion 1. The diagnosis of Clostridium difficile colitis should be suspected in patients with diarrhea and associated risk factors, even in the pediatric population. 2. The increasing incidence of Clostridium difficile infection requires the implementation of appropriate policies for antibiotic use and further studies investigating optimal therapeutic and preventive strategies.

Viral Co‐infections Are Common and Are Associated With Higher Bacterial Burden in Children With Clostridium difficile Infection

Clostridium difficile infections in children are increasing. In this cohort study, we enrolled 62 children with diarrhea and C difficile. We performed polymerase chain reaction assays to detect viral agents of gastroenteritis and quantify C difficile burden. Fifteen (24%) children diagnosed as having C difficile infection had a concomitant viral co-infection. These patients tended to be younger and had a higher C difficile bacterial burden than children with no viral co-infections (median difference = 565,957 cfu/mL; P = 0.011), but were clinically indistinguishable. The contribution of viral co-infection to C difficile disease in children warrants future investigation.

Clostridium difficile infection in children hospitalized due to diarrhea

The frequency of Clostridium difficile infection (CDI)-related hospitalizations is increasing. The aim of this study was to determine the extent of CDI among children hospitalized with diarrhea, risk factors or predictors for severe CDI, the prevalence of NAP1, and to compare the course of CDI depending on bacteria toxicity profile. A retrospective analysis of case records of 64 children (age range 3 months–16 years, median age 2.12 years) with CDI as defined by diarrheal disease and positive polymerase chain reaction (PCR) test (Xpert C. difficile) was conducted. Modified national adult guidelines were used to assess the severity of CDI. CDIs represented 2.7 % of patients with diarrhea (13.5 cases per 1,000 admissions). Thirty-three CDIs (52 %) were community-associated. Antibacterial use preceded CDI in 61 patients (95 %). Seventeen cases (27 %) were binary toxin-positive (CDT+), 13 of which were NAP1 (20.5 %). Over 75 % of CDIs with NAP1 was hospital-acquired, and more often proceeded with generalized infection (p < 0.05). Risk factors for severe CDI (34 %) included NAP1 [odds ratio (OR), 4.85; 95 % confidence interval (Cl), 1.23, 21.86) and co-morbidities (OR, 4.25; 95 % Cl, 1.34, 14.38). Diarrhea ≥10 stools daily was associated with severe CDI (p = 0.01). Recurrence occurred in three patients (4.5 %). There was no mortality. C. difficile is an important factor of antibiotic-associated diarrhea in children. Co-morbidities and NAP1 predispose to severe CDI.

Distinguishing Community-Associated From Hospital-Associated Clostridium difficile Infections in Children: Implications for Public Health Surveillance

Children are increasingly recognized as being at risk for C. difficile infection (CDI), even without prior exposure to antibiotics or the healthcare environment. We aimed to distinguish risk factors, clinical course, and outcomes between healthcare facility-associated (HA) and community-associated (CA) CDI. This was a retrospective, observational cohort study conducted at the Johns Hopkins Children's Center, Baltimore, Maryland. All inpatients, aged ≥1 year, hospitalized from July 2003 to July 2012 and diagnosed with CDI based on clinical characteristics and confirmatory laboratory testing were included. The main outcome was CDI, categorized as HA-CDI, CA-CDI, and "indeterminate" (classified as disease onset in the community, 4-12 weeks from hospital discharge). Two hundred two pediatric inpatients were diagnosed with CDI, of whom 38 had CA-CDI, 144 had HA-CDI, and 20 had indeterminate CDI. Children with indeterminate CDI had baseline characteristics similar to those identified for HA-CDI. Children hospitalized with CA-CDI were less likely to have comorbidities (odds ratio [OR], 0.14; 95% confidence interval [CI], .03-.65; P = .013), to have been exposed to antibiotics (OR, 0.17; 95% CI, .07-.44; P < .001), or prior surgeries (OR, 0.03; 95% CI, .00-.24; P = .001), compared to children with HA-CDI. Compared with HA-CDI, children with CA-CDI had a trend toward more episodes of septic shock (P = .07), toxic megacolon (P = .04), and recurrences (P = .04). In a hospitalized cohort, CA-CDI is more often seen in previously healthy children without antibiotic exposure or comorbid conditions and has more frequent complications and recurrences compared to HA-CDI. For surveillance purposes, "indeterminate" CDI should be allocated to HA-CDI rather than CA-CDI.

Editorial Commentary: Community-Associated Clostridium difficile Infection in Children

the expansion of pediatric CDI is simply a consequence of children being swept into the adult epidemic, or if the pediatric epidemic is a phenomenon all its own. Surveys of children with CDI in pediatric hospitals in areas where NAP1 was widespread in adults indicated that only approximately 10%–20% were due to the hypervirulent strain [5,7], suggesting that factors other than dissemination of NAP1 into the pediatric population were operative in driving up the incidence and severity of CDI in children. These observations support the need to conduct epidemiological studies specific to the pediatric age group. In 2005, a second facet of the evolving

Clostridium difficile Infection in Pediatric Acute Myeloid Leukemia

The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

187 Emerging Role of Fecal Microbiota Therapy in the Treatment of Recurrent Clostridium difficile Infection in Children

187 Emerging Role of Fecal Microbiota Therapy in the Treatment of Recurrent Clostridium difficile Infection in Children