Prevalence Of C. Difficile Infection Research Articles

Clostridioides difficile infection in infants: a case report and literature review

BackgroundClostridioides difficile (C. difficile) is the major pathogen causing antibiotic-associated diarrhea. There are a variety of symptoms associated with C. difficile infection (CDI) in adults, including self-limiting diarrhea, pseudomembranous colitis, toxic megacolon, septic shock, and even death from the infection. However, the infant’s intestine appears to be completely resistant to the effects of C. difficile toxins A and B with rare development of clinical symptoms.Case presentationIn this study, we reported a 1-month-old girl with CDI who was born with neonatal hypoglycemia and necrotizing enterocolitis. Her symptom of diarrhea occurred after extensive use of broad-spectrum antibiotics during hospitalization and was accompanied by elevated white blood cell, platelet, and C-reactive protein levels, and repeated routine stool examinations were abnormal. She was recovered by norvancomycin (an analogue of vancomycin) and probiotic treatment. The results of 16 S rRNA gene sequencing also demonstrated the recovery of intestinal microbiota with the enrichment of Firmicutes and Lactobacillus.ConclusionsBased on the literature review and this case report, clinicians should also pay attention to diarrhea caused by C. difficile in infants and young children. More strong evidence is needed to explain the true prevalence of CDI in this population and to better understand the C. difficile-associated diarrhea in infants.

Frequency of Clostridioides difficile Infection Among Hospitalized Patients in Kerman City, Iran

Background: Clostridioides difficile is one of the major causes of nosocomial infections, being responsible for 15 to 25% of antibiotic-associated diarrhea. It is important to determine the epidemiology and prevalence of this bacterium at hospitals and healthcare centers. Objectives: This study aims to investigate the prevalence of C. difficile infection (CDI) by identifying toxigenic isolates of C. difficile in different wards of the hospital. Methods: A total of 417 diarrheal stool samples were taken from hospitalized patients in different wards of three educational hospitals in Kerman City, Iran from 2018 to 2020. The samples were cultured on cycloserine-cefoxitin fructose agar and C. difficile suspected colonies were isolated. Identification of the cdd-3 gene for definitive diagnosis of C. difficile and identification of toxin genes in the positive isolates was performed using the PCR method. Results: A total of 68 isolates (16.3%) of C. difficile were isolated from the specimens. Besides, 8.6% (36/417) and 7.6% (32/417) of the isolates were toxigenic and nontoxigenic, respectively; thus, the prevalence of CDI was 8.6%. Most of the toxigenic isolates had the A+B+CDT- toxin phenotype. The highest prevalence of CDI was observed in males, ICU ward, and age group of 41 - 60. Conclusions: A total of 8.6% of hospitalized patients with diarrhea were infected with C. difficile. The prevalence of CDI in Kerman City is lower than that in Europe, East Asia, and other parts of Iran, but it is almost the same as that in the Middle East.

Clinical outcomes for Clostridioides difficile associated diarrhea in inflammatory bowel disease patients versus non-IBD population: A retrospective cohort study.

Patients with inflammatory bowel disease (IBD) have a higher incidence of Clostridioides difficile infection (CDI). Previous studies have demonstrated negative clinical outcomes in IBD patients with CDI compared to patients without CDI. The clinical presentation of CDI is indistinguishable from IBD exacerbation, thus posing a frequent clinical dilemma on the role of Clostridioides infection in the testing, diagnosis, and treatment of these patients. To compare clinical outcomes of CDI in patients with IBD to those without IBD. Retrospective cohort of adult patients admitted to Rabin Medical Center Israel between the years 2014 and 2020 with a concurrent diagnosis of IBD and CDI. Matching 1:2 was performed between the IBD patients and the non-IBD population with respect to age and sex. Sixty-seven patients with IBD and 134 patients without IBD were included in the study. The groups' median age was 40.6 (interquartile range [IQR] of 29.8-68.9), with 45.8% male and 54.2% female. The non-IBD group had a higher Charlson score with 2 (IQR 0; 5) versus 0 (IQR 0; 4) in the IBD group (P value <.01). Patients with IBD had more exposure to systemic antibiotics, 71.1% versus 26.3% (P value <.01). In a multivariable analysis we found no difference in 90-day mortality and rate of relapse between the 2 study groups with an odds ratio of 1.709 (95% confidence interval 0.321-9.905) and odds ratio of 0.209 (95% confidence interval 0.055-1.513) respectively. In our cohort patients with IBD who present with diarrhea and concomitant CDI have similar rates of relapse and mortality compared with patients without IBD.

High Prevalence of Multidrug-Resistant Clostridioides difficile Following Extensive Use of Antimicrobials in Hospitalized Patients in Kenya.

Introduction Clostridioides difficile is a neglected pathogen in many African countries as it is generally not regarded as one of the major contributors toward the diarrheal disease burden in the continent. However, several studies have suggested that C. difficile infection (CDI) may be underreported in many African settings. The aim of this study was to determine the prevalence of CDI in hospitalized patients, evaluate antimicrobial exposure, and detect toxin and antimicrobial resistance profiles of the isolated C. difficile strains.MethodsIn this cross-sectional study, 333 hospitalized patients with hospital-onset diarrhoea were selected. The stool samples were collected and cultured on cycloserine-cefoxitin egg yolk agar (CCEY). Isolates were presumptively identified by phenotypic characteristics and Gram stain and confirmed by singleplex real-time PCR (qPCR) assays detecting the species-specific tpi gene, toxin A (tcdA) gene, toxin B (tcdB) gene, and the binary toxin (cdtA/cdtB) genes. Confirmed C. difficile isolates were tested against a panel of eight antimicrobials (vancomycin, metronidazole, rifampicin, ciprofloxacin, tetracycline, clindamycin, erythromycin, and ceftriaxone) using E-test strips.Results C. difficile was detected in 57 (25%) of diarrheal patients over the age of two, 56 (98.2%) of whom received antimicrobials before the diarrheal episode. Amongst the 71 confirmed isolates, 69 (97.1%) harbored at least one toxin gene. More than half of the toxigenic isolates harbored a truncated tcdA gene. All isolates were sensitive to vancomycin, while three isolates (2.1%) were resistant to metronidazole (MIC >32 mg/L). High levels of resistance were observed to rifampicin (65/71, 91.5%), erythromycin (63/71, 88.7%), ciprofloxacin (59/71, 83.1%), clindamycin (57/71, 80.3%), and ceftriaxone (36/71, 50.7.8%). Among the resistant isolates, 61 (85.9%) were multidrug-resistant.ConclusionMultidrug-resistant C. difficile strains were a significant cause of healthcare facility-onset C. difficile infections in patients with prior antimicrobial exposure in this Kenyan hospital.

Multicenter study of the epidemiology of Clostridioides difficile infection and recurrence in southern Brazil

Clostridioides (Clostridium) difficile is the main etiology underlying antibiotic-associated diarrhea (AAD). Still, few Brazilian data are available on this infection. The aims of this multicenter study were to identify the prevalence, clinical characteristics, and outcomes of C. difficile infection (CDI) in patients with antibiotic associated diarrhea at eight hospitals in Curitiba, southern Brazil, during the years 2017–2019. Stool samples were tested using enzyme immunoassay for glutamate dehydrogenase antigen (GDH) and A/B toxins. Positive GDH samples were further evaluated by real-time polymerase chain reaction (PCR) for the presence of genes encoding toxin B (tcdB), binary toxin (cdt), and marker of hypervirulent C. difficile strain (tcdC deletion). The prevalence of CDI in 351 patients with AAD included in the study was 17.7% (n = 62). Among the CDI cases, tcdB was positive in all 62 stool samples, while cdt was positive in 10 samples, and tcdC deletion was positive in only two. Carriage of carbapenem-resistant Gram-negative bacilli, previous hospitalization, and use of broad-spectrum cephalosporin and carbapenem were associated with CDI. Among patients with CDI, 64.5% presented with severe diarrhea, and 8% (5/62) progressed with colitis and required intensive care. The 30-day mortality was 24% (15/62), and the CDI-associated mortality was 4.8% (3/62). Overall, 83.8% (52/62) of the patients achieved primary cure, and 20.8% of the evaluated patients (10/48) presented CDI recurrence. The treatment administered was not significantly associated with the 60-day recurrence or mortality. In conclusion, we reported in this study data of prevalence and recurrence rates of CDI in patients with AAD and evaluated the number of severe cases and infection-related mortality, which were up to now unknown in Southern Brazilian hospitals.

Burden of Clostridium Clostridioides difficile Infection among Patients in Western Asia: A Systematic Review and Meta-Analysis

Clostridium difficile is the most common causes of hospital-acquired diarrhea affecting particularly hospitalized patients globally. This organism has re-emerged in recent years with significant morbidity and mortality. The present study aimed to estimate the burden of C. difficile infection (CDI) and to acquire information on the overall rates of community- and hospital-acquired CDI in western Asia. A systematic literature search was performed to identify articles published from the eight Persian Gulf countries in western Asia including Iran, Iraq, Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates in the electronic databases within Jan of 2000 to Dec of 2017. Then, 20 publications which met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. Twenty studies reported the prevalence of toxigenic strains of C. difficile among patients from Persian Gulf countries, of these the pooled prevalence of CDI was 9% (95% CI: 6.5%-12.5%). Totally, 8 studies showed the prevalence of hospital-acquired CDI, from those studies the prevalence of CDI was estimated 8.4% (95% CI: 4.9%-14.1%). Moreover, 7 studies reported the prevalence of community-acquired CDI, from those studies the prevalence of CDI was estimated 1.8% (95% CI: 1.2%-2.9%). The prevalence of CDI in western Asia is lower than southern and eastern region. Moreover, the lower prevalence of community-acquired CDI compared to hospital-acquired CDI, indicate that the source of infection in western Asia is more likely in the hospitals.

Chlorhexidine bathing and Clostridium difficile infection in a surgical intensive care unit

BackgroundClostridium difficile is the most common causative pathogen for hospital-acquired infections in the intensive care unit. This study evaluated the effect of chlorhexidine bathing every other day in preventing hospital-acquired C. difficile infection (CDI) using data from the CHlorhexidine Gluconate BATHing (CHG-BATH) randomized trial. MethodsThe primary endpoint was the proportion of patients acquiring CDIs among patients at risk for incident CDIs. Infections detected >48 h after randomization were classified as incident CDIs. Infections detected before or within 48 h of randomization were classified as prevalent CDIs. ResultsOf 38 patients (11.7%) who met criteria for potential CDI and underwent adjudication, 24 (7.4%) received oral or enema vancomycin, 18 (5.5%) had a positive C. difficile molecular assay, 14 (4.3%) received an International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI, and 2 (0.6%) had possible pseudomembranous colitis on histopathology reports. The prevalence of CDI was 3.7% (6 of 164) in the soap and water arm and 4.3% (7 of 161) in the chlorhexidine arm. Compared with daily soap and water bathing, 2% chlorhexidine bathing every other day was not associated with the prevention of hospital-acquired CDI (1.3% [2 of 152] soap and water versus 2.0% [3 of 148] chlorhexidine, P = 0.68). ConclusionsIt is inconclusive if there was an association between chlorhexidine bathing and incidence of CDI among surgical intensive care unit patients in this study as statistical power was limited. There are limited published data evaluating the association between chlorhexidine bathing and CDI, and this study provides data for future systematic reviews and meta-analyses.

P876 Prevalence of Clostridium difficile infection among hospitalised inflammatory bowel disease patients in Greece

Clostridium difficile (C. difficile) is the leading cause of antibiotic-associated colitis and nosocomial diarrhoea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI); however, data on the prevalence of CDI in Greece are limited. We sought to determine rates of CDI among hospitalised IBD patients in major tertiary referral hospitals in Greece. We performed a retrospective analysis of stool culture results from hospitalised patients investigated for diarrhoea that were tested for CDI from January till December 2016. A rapid immunoenzymatic (EIA) assay (C.diff Quik check, Complete, Techlab, Blacksburg, VA, USA) was used to test for glutamate dehydrogenase (GDH). Toxins A and B were also sought in positive samples, in order to confirm CDI. Finally, CDI prevalence in IBD patients was compared with non-IBD patients. In total 6932 patients were tested for CDI while hospitalised. Among them, 894 patients were found positive for GDH (12.89%), while 339 were also found positive for C. Difficile toxin (4.89%). Therefore, the prevalence of CDI among all hospitalised patients was 1.6/1000 patient-days. Among them, there were 401 IBD patients presenting with diarrhoea and tested for CDI. Sixty-two patients were found positive for GDH (15.46%), while 30 were also found positive for C. difficile toxin (7.48%). Therefore, the prevalence of CDI in IBD patients was 2.5/1000 patient-days. The prevalence of CDI among IBD hospitalised patients was significantly higher than non-IBD hospitalised patients (30/401 vs. 309/6531, p = 0.013). Among the 30 IBD patients with CDI, there were 14 men and 16 women, with a mean age of 46 years. Eighteen of them had ulcerative colitis (E1 = 2, E2 = 3, E3 = 13) and 12 Crohn’s disease (A2L1B1 = 3, A2L2B1 = 3, A2L3B1 = 3, A3L1B1 = 2, A3L3B3 = 1). Six of them were receiving biologics, 3 were receiving corticosteroids (one with azathioprine and one with 5-ASA), 9 were on azathioprine monotherapy and 12 on 5-ASA monotherapy. CDI was successfully treated with metronidazole and/or vancomycin in all cases. Data from IBD referral tertiary Greek hospitals show that CDI prevalence is higher in hospitalised IBD patients than those without IBD. CDI is a growing public health issue among hospitalised IBD patients, prompting the need for better preventative measures, as well as for early detection and treatment.

Prevalence of Clostridium difficile infection among the patients attending a tertiary care teaching hospital.

Clostridium difficile, a most important nosocomial enteric pathogen, is recognized globally as responsible for antibiotic-associated diarrhea and colitis. It is associated with considerable morbidity and mortality due to widespread use of antibiotics. The study was done to determine the prevalence of C. difficile infection (CDI) among the patients attending a tertiary care teaching hospital in Puducherry. We performed a prospective cohort study in Mahatma Gandhi Medical College and Research Institute. Around 150 patients were evaluated along with the patient details. C. difficile toxin detection was done as per the standard algorithm using the C. Diff Quik Chek Complete® assay (TECHLAB, Blacksburg, VA, USA). Analysis was done using statistics software (SPSS 16.0, SPSS Inc., Chicago, IL, USA). The prevalence of CDI was found to be 4%. More toxin-positive cases were between 50 and 60 years of age, and there was no difference in gender. Intensive Care Unit showed more toxin-positive cases; however, there was no significant association between the occurrence of CDI and the primary diagnosis of the patients. The prevalence of CDI in our hospital was found to be 4%, which was relatively lower compared to other Indian studies. However, awareness of the risk factors may assist in identifying patients at higher risk for CDI, guide implementation of appropriate preventive measures, and modulate potential intervention measure during management.

Does Obesity Influence the Risk of C. difficile Infection Among Patients with Ulcerative Colitis?

Introduction: Patients with ulcerative colitis (UC) are at an increased risk C. difficile infection (CDI) compared with the general population. Recent data suggests that obesity also increases the risk of CDI. The purpose of this study was to examine whether obesity influences the risk of CDI among patients with UC. Methods: We performed a retrospective cross-sectional study of 636 patients with ulcerative colitis seen at an outpatient gastroenterology clinic between January 1, 2014 and December 31, 2015. Electronic medical records (EMR), available after 2010, were reviewed for UC patients. Body mass index (BMI) was used to define underweight (BMI < 18.5), normal weight (18.5≤BMI < 25), overweight (25≤BMI < 30), and obese (BMI≥30). Unpaired t-test, chi-squared analysis, and ANOVA were used for between-group comparisons. Multivariate logistic regression included age, gender, tobacco use, UC disease duration, TNF or vedolizumab exposure, and vitamin D deficiency. Log likelihood ratio test for linear trend was used to evaluate BMI and CDI risk. Results: Cohort demographics included average patient age 54 (SD 17), 48% male, 4.3% active tobacco use, UC disease duration 15.2 years (SD 12.5), and 318 (51%) with extensive UC, and did not differ between patients with and without CDI. 114 (18%) were classified as obese, 232 (36%) overweight, 274 (43%) normal weight, and 16 (2.5%) underweight. Nineteen patients (3.0%) developed CDI during the study period, 5 (26%) of which were hospitalized within 6 months prior to CDI. Three patients had Mayo 0 endoscopic subscore and histologic remission within one year of CDI diagnosis. At time of CDI diagnosis, 5 (26%) were on antibiotics, 5 (26%) were on TNF (2 on combination therapy with thiopurine), and 1 on tofacitinib. Six (32%) patients developed UC flare attributed to CDI. CDI risk was not affected by BMI (OR 0.90, 95% CI 0.79-1.02). Compared to normal weight patients, risk of CDI was not influenced by obesity (OR 0.64, 95% CI 0.15-2.67), or being overweight (OR 0.33, 95% CI 0.08-1.32) or underweight (OR 3.08, 95% CI 0.44-21.81). There was no significant trend towards CDI risk based on BMI category. Ever use of TNF therapy was associated with CDI on univariate (OR 5.41, 95% CI 2.13-13.71) and multivariate (OR 7.91, 95% CI 2.71-23.07) analyses. Conclusion: Although limited by low prevalence of CDI, obesity does not appear to influence the risk of CDI among patients with UC.

Practice parameters for the management of Clostridium difficile infection.

Steele, Scott R. M.D.; McCormick, James D.O.; Melton, Genevieve B. M.D.; Paquette, Ian M.D.; Rivadeneira, David E. M.D.; Stewart, David M.D.; Buie, W. Donald M.D.; Rafferty, Janice M.D. Author Information

Circulating Antibody and Memory B-Cell Responses to C. difficile Toxins A and B in Patients with C. difficile-Associated Diarrhoea, Inflammatory Bowel Disease and Cystic Fibrosis

C. difficile infection (CDI) is rarely reported in cystic fibrosis (CF) patients despite frequent hospitalisations and antibiotic usage. Conversely, the prevalence of CDI in inflammatory bowel disease (IBD) has received increased attention. We investigated components of the IgG-specific humoral immune response to C. difficile toxins A and B in patients with C. difficile-associated diarrhoea (CDAD), IBD patients with CDI, CF patients and healthy controls. Serum anti-toxin IgG was determined by ELISA. Circulating antigen-activated B-cells were investigated using Alexa Fluor 488-labelled toxin A and assessed by flow cytometry. Following induction of differentiation of memory B-cells, toxin A- and B-specific antibody secreting cells (ASCs) were quantified using ELISpot. We present the first data showing levels of serum anti-toxin A and B antibodies were significantly higher in patients with CF (without a history of CDI) than in CDAD patients and were stably maintained over time. Notably, the CDAD patients were significantly older than the CF patients. We also show that circulating toxin A-specific memory B-cells (IgD-negative) can be detected in CDAD patients [0.92 (0.09–1.78)%], and were prominent (5.64%, 1.14%) in two CF patients who were asymptomatic carriers of C. difficile. There was correlation between toxin A- and B-specific ASCs, with significantly higher proportions of the latter seen. In some with CDAD, high serum antibody levels were seen to only one of the two toxins. Mucosal secretion of toxin-specific IgG was detected in an additional group of IBD patients with no history of CDI. We conclude that enhanced and stable humoral immune responses to toxins A and B may protect CF and some IBD patients against CDI. The impaired ability to generate strong and/or sustained toxin-specific antibody and memory B-cell responses may increase susceptibility of older patients to CDI and highlight the need to investigate the role of immune senescence in future studies.

Clostridium difficileand inflammatory bowel disease: Role in pathogenesis and implications in treatment

Clostridium difficile (C. difficile) is the leading cause of antibiotic associated colitis and nosocomial diarrhea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI), have worse outcomes of CDI-including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether C. difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment. The burden of CDI has increased dramatically over the past decade, with severe outbreaks described in many countries, which have been attributed to a new and more virulent strain. A parallel rise in the incidence of CDI has been noted in patients with IBD. IBD patients with CDI tend be younger, have less prior antibiotic exposure, and most cases of CDI in these patients represent outpatient acquired infections. The clinical presentation of CDI in these patients can be unique-including diversion colitis, enteritis and pouchitis, and typical findings on colonoscopy are often absent. Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation, and the prognostic implications of CDI in these patients, it is recommended to test all IBD patients hospitalized with a disease flare for C. difficile. Treatment includes general measures such as supportive care and infection control measures. Antibiotic therapy with either oral metronidazole, vancomycin, or the novel antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI. The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.

Antibodies to Clostridium difficile Toxins in Inflammatory Bowel Disease Patients

Purpose: In non-Inflammatory Bowel Disease (IBD) patients, asymptomatic Clostridium difficile colonization (CDC) and anti-Clostridium difficile (C. difficile) toxin antibodies are protective against symptomatic C. difficile infection (CDI). Yet, in IBD patients, an increased rate of colonization is associated with an increased prevalence of CDI. Whether or not anti-toxin antibodies can explain this relationship remains unknown. The objective of this study is to (1) determine rates of CDC and CDI in a cohort of IBD patients in a subspecialty outpatient clinic and (2) compare serum anti-C. difficile toxin antibody IgG, IgM and IgA levels between the IBD and non-IBD cohort. Methods: This is an ongoing prospective IRB approved observational cohort study that has enrolled 75 of an expected 120 IBD patients and 10 of an expected 60 non-IBD controls. Patient demographics, medications, disease severity and known risk factors for CDI were recorded. Stool was tested for C. difficile DNA by PCR with strain typing for presumptive hypervirulent NAP1/027 (Xpert C. difficile/Epi®-Cepheid, Sunnyvale, CA). Serum antibody titers of IgG, IgM and IgA against C. difficile toxins A and B were tested. Only subjects with both stool and blood samples (n=57) were included in this interim analysis. As antibody measurements were not normally distributed the Wilcoxon's rank sum test was used to compare mean optical density (OD) concentrations. Results: Fifty-one IBD patients (23 Crohn's disease, 15 ulcerative colitis, 13 ileal pouch) and 6 non-IBD controls submitted both stool and blood samples. The mean age of IBD patients and controls were 45 years old (range 19-76) and 43 years old (range 25-61) respectively. In the IBD cohort, there was 5 CDI (9.8%) and 3 CDC (5.8%) patients. The control group had 1 CDC and no CDI subjects. There was no hypervirulent NAP1/027 strain in either cohort. In preliminary analyses, compared to non-IBD subjects, ulcerative colitis patients had lower IgA to toxin A (mean OD 0.93 vs. 1.32; p=0.03) and lower IgG to toxin B (mean OD 0.70 vs. 0.82; p=0.04). Conclusion: In this cohort of IBD subjects, CDC and CDI rates were similar to those reported in other studies. Hypervirulent strains were not found. UC patients had a significantly lower IgA antibody titers to toxin A and lower IgG to toxin B compared to non-IBD subjects. This finding is in contrast to other studies that reported higher antibody levels in IBD patients. Additional studies are needed to clarify if IBD patients have a blunted antibody response to toxin A or B and whether this is clinically significant. Disclosure: Ciaran P Kelly, MD 2010-Claremont BioSolutions - Research support 2011-GSK - Consultant, advisory board member 2011-Merck - Research support, consultant, advisory board member 2011-Optimer - Research support, advisory board member 2011-Sanofi-Pasteur - Research support, consultant 2010-Viro Pharma Inc - Consultant, advisory board member 2011-CSL Behring - Research support, consultant 2011-Pfizer - Consultant 2011-Wyeth - Consultant 2012-Astellas - Consultant Francis A Farraye, MD, MSc 2012 Cepheid-Research support.

Protection Against Clostridium difficile Infection With Broadly Neutralizing Antitoxin Monoclonal Antibodies

The spore-forming bacterium Clostridium difficile represents the principal cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. C. difficile infection (CDI) is mediated by 2 bacterial toxins, A and B; neutralizing these toxins with monoclonal antibodies (mAbs) provides a potential nonantibiotic strategy for combating the rising prevalence, severity, and recurrence of CDI. Novel antitoxin mAbs were generated in mice and were humanized. The humanized antitoxin A mAb PA-50 and antitoxin B mAb PA-41 have picomolar potencies in vitro and bind to novel regions of the respective toxins. In a hamster model for CDI, 95% of animals treated with a combination of humanized PA-50 and PA-41 showed long-term survival relative to 0% survival of animals treated with standard antibiotics or comparator mAbs. These humanized mAbs provide insight into C. difficile intoxication and hold promise as potential nonantibiotic agents for improving clinical management of CDI.

High Proportion of False-Positive Clostridium difficile Enzyme Immunoassays for Toxin A and B in Pediatric Patients

To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity. Nested case-control. Two tertiary care pediatric hospitals. As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays. Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%-7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii. Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.

High prevalence of toxinogenic Clostridium difficile in Nigerian adult HIV patients

Clostridium difficile is the most commonly identified bacterial cause of nosocomial and HIV-related diarrhea. In many developing countries, antibiotic access is unregulated. Nigeria has the third highest HIV burden worldwide. Due to perceptions of low prevalence and resource incapacity, patients with diarrhea are not tested for toxinogenic C. difficile infection (CDI). In this pilot study which included 97 HIV-positive patients at two hospitals in Nigeria, the estimated prevalence of CDI was 43% and 14% for in-patients and out-patients respectively. HIV-positive out-patients were more likely to have toxinogenic CDI than non-HIV out-patients ( P = 0.007, Fisher's exact test).

C. difficile infection (CDI) in a long-term acute care facility (LTAC)

Background C. difficile infection (CDI) is a common nosocomial infection in hospitals and impacts increased hospital cost and length of stay. Since scant information is available about the incidence and prevalence of CDI in Long-term acute care hospitals (LTACs), we therefore studied this at one local facility. Methods Demographic and other data, and a fresh stool sample were obtained from all new LTAC admissions not carrying a prior diagnosis of CDI during the study period (July 23 to August 22, 2007). A GDH test for C. difficile antigen was performed. All initially positive stools were tested for toxins A and B and a sample was frozen for culture and typing. All antigen-negative patients were monitored for the development of diarrhea during the course of their LTAC hospitalization and, if clinically indicated, a sample was sent for toxins A and B testing and if positive, a stool sample was frozen and stored for culture and typing. Therapy of CDI was noted. Results 36 patients were admitted during the study period. 4 of 31 (12.9%) of patients tested were antigen (+) on admission of which 2 (6.5%) were asymptomatic carriers and 2 (6.5%) had unsuspected active disease, including one with the BI epidemic strain. In follow-up, 20/36 (55.5%) developed diarrhea of which an additional 5 (13.8%) patients had developed CDI (average, hospital day 38) in the hospital. Therapy was instituted with vancomycin in 5/7 patients and metronidazole in 2/7 patients. During that quarter, the rate of nosocomial acquired CDI was 3.12 per 1000 patient days. Conclusions C. difficile carriage and unsuspected clinical CDI occurs, including with the BI epidemic strain disease, in an important minority of patients, which may act as a reservoir for spread. New strategies for detection and prevention of CDI are needed.