Community-acquired Clostridium Difficile Infection Research Articles

Epidemiologic and Clinical Characteristics and Risk Factors for Severe Community-Acquired Clostridium Difficile Infection in Children.

Although children most frequently suffer from milder forms of community-acquired Clostridium difficile infection, severe cases and fatal outcomes have been recorded. In this study we identified older children (>12 years of age) and patients who had surgery up to 6 months before Clostridium difficile infection onset as a subgroup at somewhat higher risk for severe community-acquired Clostridium difficile infection.

The incidence of Clostridium difficile infection in children with and without inflammatory bowel diseases: A single-center study in Taiwan from 2006 to 2019

BackgroundThe incidence of Clostridium difficile infection (CDI) is increasing around the world, and patients with inflammatory bowel disease (IBD) have a higher risk of obtaining CDI. The data on the incidence rate of CDI in the Asian pediatric IBD population was lacking. MethodsWe retrospectively collected data from a tertiary medical center in Taipei, Taiwan. All patients aged 1–18 years old who visited the outpatient department or were admitted to our hospital between 2006 and 2019 were included. CDI was defined as positive stool C. difficile toxin or C. difficile culture results with appropriate antibiotic use within the range of 7 days prior or 14 days after the result. ResultsWe compared the average annual incidence of CDI before and after 2013. The average incidence of community-acquired CDI (CA-CDI) increased from 0.063 to 0.564 cases per 1,000 visits, with a rate ratio (RR) of 8.82 (95% CI 5.74-14.38). In patients with IBD, the rate increased from 26.738 to 278.873 cases per 1,000 visits (RR=10.12, 95% CI: 4.57-29.02). The average incidence rate increased from 0.685 to 1.874 cases per 1,000 admissions in pediatric general patients (RR = 2.72, 95% CI 1.82-4.20) and from 14.706 to 62.500 cases per 1,000 admissions in pediatric IBD patients (RR = 3.77, 95% CI 0.71-93.53). ConclusionsBoth CA-CDI and healthcare facility-onset CDI (HO-CDI) were increasing substantially in the pediatric population over the past decade in Taiwan. Compared to the general pediatric population, pediatric IBD patients had a much higher incidence of CDI.

Prognostic factors for severe course and adverse outcome of Clostridium difficile infection after Covid 19

Before the Covid 19 pandemic, the incidence of community-acquired Clostridium difficile infection (CDI) was 35-50%. SARS-CoV-2 created favorable conditions for its increase. Aim: To identify the factors responsible for the severe course and adverse outcome in CDI post-Covid 19. Materials and methods: 121 patients aged from 23 to 90 years-53 women and 68 men - with CDI and a recent Covid-19 were included in a prospective study. Clinical, epidemiological, laboratorial and molecular-genetic investigations were used. Results: All patients were on long-term treatment with broad-spectrum antibiotics for SARS-CoV-2 infection. The most common symptoms of CDI were diarrhea, fever and loss of weight. The majority of patients were discharged in an improved condition. There were 12 lethal outcomes (9,91%). Conclusion: Age over 65 years, presence of accompanying chronic diseases, as well as late hospitalization can be indicated as poor prognostic factors for the clinical course and outcome of CDI.

Analysis of risk factors for community-acquired Clostridioides difficile diarrhea in children: a case-control study in Chenzhou, China.

Most previous studies on Clostridium difficile infection (CDI) mainly focused on adults with underlying diseases or critical illnesses. However, the number of CDI cases in children has also significantly increased, especially the growth of community-acquired CDI, which has attracted attention. This study was conducted to examine the toxin gene characteristics and the risk factors associated with community-acquired CDI (CA-CDI) in children with diarrhea. Children with diarrhea before admission or within 48 hours of hospitalization were included in the study. Stool samples were collected from children with community-acquired diarrhea who were treated at the Children's Hospital of the First People's Hospital of Chenzhou, China from June of 2021 to June of 2022. Fluorescence real-time polymerase chain reaction was utilized to detect Clostridioides difficile (CD) toxins A (tcdA) and B (tcdB) genes as well as binary toxin gene A (cdtA) and B (cdtB) in the specimens cultured for CD. Each child with CA-CDI was matched with four control children of the same sex, age, and place of residence. Necessary clinical data were extracted from the hospital's electronic medical record system. Then, a multivariate conditional logistic regression analysis was applied to identify potential risk factors for CA-CDI. Sixteen (8.3%) of the 193 stool specimens who tested positive for CD were selected for the case group, and their matching 64 control patients were in the study cohort. The breakdown of the CD genotypes of the 16 positive cases were follows: 14 (tcdA+ and tcdB+) (7.25%) and 2 (tcdA+ and tcdB-) (1.04%). The cdtA and cdtB binary toxin genes were negative in all. The results of multivariate conditional logistic regression analysis identified antibiotic use within the previous month [odds ratio (OR) =5.13; 95% confidence interval (CI): 1.65-15.91] and non-breastfeeding (OR =4.89; 95% CI: 1.11-21.53) as independent risk factors for CDI in pediatric patients experiencing community-acquired diarrhea. Children who had been treated with antibiotics and not breastfed were more susceptible to CDI. Therefore, in order to prevent and to control the spread of CD infection, being prudent to the aforementioned high-risk factors is strongly advocated in clinical practice.

Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients.

Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). Machine learning-augmented multivariable regression and propensity score (PS)-modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. Among 46735 colectomy patients meeting study criteria, mean age was 61.7years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.

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.

Recurrent community-acquired Clostridium(Clostridioides)difficile infection in Serbianchildren.

Information on recurrent Clostridium difficile infections (rCDI) in children is rare and limited, especially community acquired (CA-CDI).This study was designed to identify risk factors for rCA-CDI in Serbian pediatric population. The study group included 71 children (aged from 1 to 14years) with a first episode of CDI. Data were collected from 56 (78.87%) children with only one episode of CA-CDI and from 15 (21.13%) children with rCA-CDI were mutually compared. The following parameters were found to be statistically significantly more frequent in the children with rCA-CDI group (p < 0.05); leukemia as underlying disease, treatment with immunosuppressive and-or cytostatic drugs, and treatment with antibiotics. Similarly, previously visits to outpatient facilities, daycare hospitals and hospitals were also associated with rCDI. Analysis of clinical symptoms and laboratory parameters, revealed a statistically significant association of the severity of the first episode of CDI (determined by an increase in body temperature, higher maximum WBC and higher CRP) with development of a rCDI. Ribotype (RT) 027 was more common in children with rCA-CDI (66.7%, p = 0.006). During the seven-year research period, we found a rate of rCA-CDI rate in children of 21.13%. Our study identified several parameters statistically significantly more frequently in children with rCA-CDI. The obtained results will serve as a basis for future larger studies, but new prospective, studies are necessary to build a prediction model of rCDI in children that can be used to guide the treatment to prevent rCDI.

Direct cost of health care for individuals with community associated Clostridium difficile infections: A population-based cohort study

BackgroundEven though the incidence of community-acquired Clostridium difficile infection (CDI) is reported to be increasing, few studies have reported on the healthcare costs of community-acquired CDI. We estimated cost of care for individuals with community-associated CDI and compared with that for matched controls without CDI in the time period of six months before to one year after CDI.MethodsAll individuals in the province of Manitoba, diagnosed with CDI between July 2005 and March 2015 were matched up to 4 individuals without CDI. Health care utilization and direct costs resulting from hospitalizations, physician reimbursement claims and prescriptions were determined from the population based provincial databases. Quantile regressions were performed to determine predictors of cost of individuals with community associated CDI.ResultsOf all CDIs, 30–40% in each period of the study had community-associated CDI; of which 12% were recurrent CDIs. The incremental median and 90th percentile cost of care for individuals with community-associated CDI was $800 and $16,000 respectively in the six months after CDI diagnosis. After adjustment for age, co-morbidities, sex, socioeconomic status and magnitude of health care utilization prior to CDI, the median incremental cost for recurrent CDI was $1,812 and that for a subsequent episode of CDI was $3,139 compared to those with a single community-associated CDI episode. The median cost for a prescription of Vancomycin was $316 (IQR 209–489).ConclusionsHealth care costs of an episode of community-associated CDI have been much more than the cost of antibiotic treatment. Our study provides population-based data for formal cost effectiveness analysis for use of newer treatments for community-associated CDI.

216 Determinants of Hospital Admission in Patients With Community-Acquired Clostridium difficile Infection (CA-CDI)

INTRODUCTION: Community-acquired Clostridium difficile infection (CA-CDI) is defined as Clostridium difficile infection (CDI) in patients who have not been in inpatient setting within 90 days of being tested positive for Clostridium difficile. The incidence of CA-CDI has been increasing in young individuals with no co-morbidities or recent antibiotic exposure. Recent research shows that up to 40% patients with CA-CDI need hospitalization, however, the risk factors associated with hospitalization of patients who test positive for CDI in outpatient setting has not been studied. The goal of this study is to look at patients diagnosed with CDI initially as outpatients and analyze the risk factors associated with hospitalization in these patients. METHODS: This study was approved by the Institutional Review Board. This is a retrospective chart review of 524 patients (189 males, 335 females, mean age 60 years) who were seen in the outpatient department from 2015 to 2018 and were tested for CDI. Inclusion criteria was patients over the age of 18 with positive C. difficile by nucleic acid amplification tests (NAATs). Exclusion criteria was prior diagnosis of C. difficile. For patients with positive C. difficile, the two outcomes selected were hospital admission within 2 weeks, and those remaining outpatients. The variables extracted from the electronic medical record included demographics, medications and co-morbidities. Utilizing a machine-learning algorithm, a Bayesian probabilistic predictive tool was constructed that evaluated a series of variables and their association with potential outcomes. RESULTS: Of the 524 patients that tested positive, 105 patients required admission within two weeks of diagnosis. The incidence of hospitalization among males and females was not significantly different. There was significant association between use of acid suppression medications (pantoprazole and famotidine) and risk of hospitalization for C. difficile (P-value &lt;0.0001 and 0.002 for pantoprazole and famotidine, respectively). There was no association seen between co-morbidities such as coronary or carotid artery disease, peripheral vascular disease, diabetes mellitus and the risk of hospitalization. CONCLUSION: Although PPIs have been associated with increased risk of developing CDI, our study shows that acid suppression medications may also increase the risk of hospitalization for CDI. Providers should consider the risk versus benefit of continued use of acid suppression medications in patients with CDI.

An insight into Clostridium difficile infection: a single-center retrospective case-control study.

Clostridium difficile infection (CDI) has become a worldwide health problem in view of its significant incidence and medical and economic impact on the health system. Prior studies have been undergone about risk factors and disease characteristics. We wanted to study the characteristics, prognostic factors associated with CDI at our institute, as well as a new prognostic factor. Our study aimed at describing the risk factors, patient characteristics, and outcomes associated with healthcare facility-acquired CDI (HCFA-CDI) and community-acquired CDI (CA-CDI). We intended to identify the factors associated with worse outcomes. We evaluated the characteristics associated with CDI over 3 years. We also evaluated a simple neutrophil-lymphocyte ratio (NLR) and its predictive value for worse outcomes. Six hundred patients were enrolled (333 in a control group; 171 in the HCFA-CDI group and 96 in the CA-CDI group). NLR > 5 predicted increased mortality and intensive care unit transfer in all CDI if done as early as day 2 after CDI diagnosis. In HCFA-CDI, NLR > 5 predicted a higher ICU transfer if done as early as day 1 post-diagnosis and with increased mortality as early as day 2 post-diagnosis. In CA-CDI, NLR > 5 predicted a higher mortality and ICU transfer if done at least 4days after diagnosis. Moreover, every 10-unit increase in NLR was associated with a significant increase in mortality and ICU transfer in patients with CDI. A timely use of NLR can be used as a mean to predict worse outcomes, namely ICU transfer and mortality, in patients with CDI.

425 Is the Use of Proton Pump Inhibitors Associated With Increased Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis

INTRODUCTION: The use of proton-pump inhibitors (PPIs) has been associated with various adverse effects including increased risk of major adverse cardiovascular events, community acquired clostridium difficile infection, chronic kidney disease and dementia. Some studies over the past decade have suggested an association between PPIs use and ischemic stroke. METHODS: We pooled the data after comprehensive literature search from the PubMed, Embase, Cochrane Library and Scopus databases using ‘proton pump inhibitors’ AND ‘stroke’ as the keywords. RevMan was used for the entry and analysis of data. A random effects model was created given the significant heterogeneity of the included studies and a funnel plot was made to assess the publication bias. Our primary objective was to study whether all-comers patients on PPIs are at an increased risk of stroke. Sub-group analysis was also done to investigate the association between patients on dual anti-platelet therapy [DAPT] (aspirin and clopidogrel) with or without PPIs and stroke. RESULTS: After searching 774 titles, 25 titles were selected to be included in the systematic review and 15 articles for the meta-analysis. Our pooled analysis of 155,406 patients (46,652 patients on PPI and 101,892 patients without PPI found a positive association between the use of PPI and stroke (odds ratio = 1.28, 95% confidence interval = 1.12, 1.48, P = 0.001) [Figure 1]. Given the significant heterogeneity of the studies (I2= 60%) a sub-group analysis was done which also suggested an increased risk of stroke associated with PPI use among patients on dual antiplatelet therapy (OR: 1.43, 95% CI: 1.26, 1.66, p&lt; 0.001, I2= 11%) [Figure 2]. Analysis of the included randomized controlled trials revealed an OR: 1.47, 95% CI: 0.66, 3.25 but the results were not statistically significant (p&lt; 0.81) [Figure 3]. CONCLUSION: In a pooled analysis of over 155,000 patients we found a positive association between the use of PPIs and stroke. Our results are limited by significant heterogeneity and retrospective study design of the observational studies. Rigorous clinical trials are needed to establish the safety of PPIs in relation to stroke, especially among patients on DAPT. Until definitive data emerges, patients on DAPT are probably best served by being off PPIs or being on alternative acid suppression regimen, unless there is a compelling indication for PPI use.

Ribotype variability of Clostridioides difficile strains in patients with hospital-acquired C. difficile infections, community-acquired C. difficile infections, and colonization with toxigenic and non-toxigenic strains of C. difficile

There have been few available data that presented a direct comparison between polymerase chain reaction ribotype (RT) distribution of Clostridioides difficile strains from C. difficile infection (CDI) and colonization. To understand the epidemiology of CDI in a hospital setting, we compared RTs of C. difficile strains from hospital-acquired CDI (HA-CDI) and toxigenic colonization and from community-acquired CDI (CA-CDI) and non-toxigenic colonization using the stool samples submitted for C. difficile cultures at an institution during 2009, 2012, and 2014. Overall, 721 C. difficile strains were identified from 607 patients. Among them, 450 (62.4%) were HA-CDI, 20 (2.8%) were CA-CDI, 126 (17.5%) were toxigenic colonization, and 125 (17.3%) were non-toxigenic colonization. RT018, RT017, RT002, RT015, and RT001 isolates were the most prevalent RTs in HA-CDI, and they comprised 74.9% of the total HA-CDI isolates but accounted for 60.4% of isolates from toxigenic colonization. In total, 32 strain compromising 18 RTs from HA-CDI (7.1%) were not seen among the toxigenic colonization group, and 3 RTs with 5 strains from toxigenic colonization were not seen among the HA-CDI group. The distribution of RTs was the most diverse in CA-CDI and the least diverse in HA-CDI. Although 5 RT strains, which were prevalent in HA-CDI, comprised 40% of CA-CDI, 5 isolates (25%) revealed unknown RTs, which were uncommon in HA-CDI or toxigenic colonization. In 12 patients with both episodes of CDI and toxigenic colonization, 8 had 2 isolates with different RTs and 4 had isolates with identical RTs. In conclusion, although RT017 and RT018 were the most common in HA-CDI and toxigenic colonization, C. difficile strains from toxigenic colonization were more diverse than those from HA-CDI.

Su1958 – Geospatial Distribution and Trends in Community Acquired Clostridium Difficile Infections: A Population-Based Retrospective Study

Su1958 – Geospatial Distribution and Trends in Community Acquired Clostridium Difficile Infections: A Population-Based Retrospective Study

Seasonality and community interventions in a mathematical model of Clostridium difficile transmission

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea with peak incidence in late winter or early autumn. Although CDI is commonly associated with hospitals, community transmission is important. To explore potential drivers of CDI seasonality and the effect of community-based interventions to reduce transmission. A mechanistic compartmental model of C.difficile transmission in a hospital and surrounding community was used to determine the effect of reducing transmission or antibiotic prescriptions in these settings. The model was extended to allow for seasonal antibiotic prescriptions and seasonal transmission. Modelling antibiotic seasonality reproduced the seasonality of CDI, including approximate magnitude (13.9-15.1% above annual mean) and timing of peaks (0.7-1.0 months after peak antibiotics). Halving seasonal excess prescriptions reduced the incidence of CDI by 6-18%. Seasonal transmission produced larger seasonal peaks in the prevalence of community colonization (14.8-22.1% above mean) than seasonal antibiotic prescriptions (0.2-1.7% above mean). Reducing transmission from symptomatic or hospitalized patients had little effect on community-acquired CDI, but reducing transmission in the community by ≥7% or transmission from infants by ≥30% eliminated the pathogen. Reducing antibiotic prescription rates led to approximately proportional reductions in infections, but limited reductions in the prevalence of colonization. Seasonal variation in antibiotic prescription rates can account for the observed magnitude and timing of C.difficile seasonality. Even complete prevention of transmission from hospitalized patients or symptomatic patients cannot eliminate the pathogen, but interventions to reduce transmission from community residents or infants could have a large impact on both hospital- and community-acquired infections.

Community-acquired fulminant colitis caused by binary toxin-producing Clostridium difficile in Japan

We report a case of community-acquired fulminant colitis caused by Clostridium difficile in Japan. A 46-year-old woman was diagnosed with severe infectious enterocolitis and was admitted at another hospital. The stool culture was positive for toxigenic C. difficile. Since the patient presented with fulminant C. difficile infection (CDI) with toxic megacolon, respiratory insufficiency, and circulatory failure, she was transferred to Kyorin University Hospital for intensive care. Intubation and antibiotic therapy were performed. The general condition improved with conservative treatment, and she was discharged without sequelae. While the recovered isolate was toxin A and B-positive and binary toxin-positive, it was identified as polymerase chain reaction (PCR) ribotype ts0592 and slpA sequence type ts0592. The isolate was different from PCR ribotype 027 epidemic in Europe and North America. In Japan, binary toxin-producing strains are rare and have not caused an epidemic to date. Furthermore, there are few data on community-acquired CDI in Japan. In this case, a non-elderly woman with no major risk factors such as antibiotic use, administration of proton pump inhibitor and history of gastrointestinal surgery developed community-acquired fulminant CDI caused by the binary toxin-positive strain, and ICU treatment was required. Further studies focusing on the role of binary toxin-positive C. difficile in the severity of community-acquired CDI are necessary.

Toxigenic Clostridium difficile carriage in general practice: results of a laboratory-based cohort study

ObjectivesReported rates of community-acquired Clostridium difficile infections (CDIs) have been increasing. However, the true burden of the disease in general practice is unknown in France. Our objective was to determine the incidence of toxigenic C. difficile carriage and the percentage of stool samples prescribed by general practitioners (GPs) which contained free C. difficile toxins. MethodsDuring an 11-month period, all stool samples submitted for any enteric pathogen detection to 15 different private laboratories in Paris and the surrounding areas were tested for C. difficile, irrespective of the GPs' request. A clinical questionnaire was completed for each patient. Stool samples were screened using a rapid simultaneous glutamate dehydrogenase and toxins A/B detection test: any positive result (glutamate dehydrogenase or toxin) was further confirmed by the stool cytotoxicity assay (CTA) on MRC-5 cells and by toxigenic culture (TC) at a central laboratory. The C. difficile isolates were characterized by PCR ribotyping. ResultsA total of 2541 patients (1295 female, 1246 male) were included. The incidences of patients with a positive toxigenic culture and a positive CTA were 3.27% (95% CI 2.61%–4.03%) and 1.81% (95% CI 1.33%–2.41%), respectively. GPs requested C. difficile testing in only 12.93% of the stool samples, detecting 52.30% of all TC-positive patients. The 83 toxigenic C. difficile strains belonged to 36 different PCR ribotypes. ConclusionsToxigenic C. difficile carriage is frequent in general practice but remains under-recognized. It may affect young patients without previous antimicrobial therapy or hospitalization.

Analysis of Treatment Outcomes for Recurrent Clostridium difficile Infections and Fecal Microbiota Transplantation in a Pediatric Hospital

Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It's imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired CDI (HA-CDI) and community-acquired CDI (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT) and compare their success rates. A retrospective cohort study of pediatric patients 1-21 years of age treated for CDI at a single institution from January 2010 to December 2014 was performed. There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least 1 documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (odds ratio: 0.39; 95% confidence interval: 0.18-0.85; P = 0.018). The overall success rate for FMT at our institution was 10/12 (83%). Our data show that cases of HA-CDI were less likely to recur compared with CA-CDI. Although currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.

Long-term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa. A Critically Appraised Topic.

Can therapy with clindamycin and rifampicin be safely continued long term beyond the recommended 10-week course? Clindamycin and rifampicin are used in combination to treat hidradenitis suppurativa (HS). There is no data on the efficacy and safety of clindamycin/rifampicin combination therapy for HS beyond 10 weeks. We identified the following major concerns that still lack a proper evidenced-based analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern was community-acquired Clostridium difficile infection (CA-CDI); and experience with long-term treatment. Data sources were used as appropriate to answer the question. Systematic searches were used to assess the risk of CA-CDI and experience with long-term treatment with clindamycin. The risk for rifampicin-induced liver injury is highest in the first 6 weeks of treatment, whereas interstitial nephritis is primarily observed during intermittent treatment. Enzyme induction due to rifampicin is usually complete after about 2 weeks of treatment and reduces clindamycin blood levels by about 90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI. Two of them assigned the highest risk to clindamycin. None of them stratified by length of treatment. There is extensive experience with rifampicin, primarily for the treatment of tuberculosis. Long-term experience with clindamycin is limited. The analysed risks associated with a combination of clindamycin and rifampicin for hidradenitis suppurative cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if clinically necessary.

Epidemiological and genomic characterization of community-acquired Clostridium difficile infections

BackgroundClostridium difficile infection (CDI) is a major cause of morbidity and mortality in North America and Europe. The aim of this study was to identify epidemiologically-confirmed cases of community-acquired (CA)-CDI in a large North American urban center and analyze isolates using multiple genetic and phenotypic methods.MethodsSeventy-eight patients testing positive for C. difficile from outpatient clinics were further investigated by telephone questionnaire. CA-CDI isolates were characterized by antibiotic susceptibility, pulsed-field gel electrophoresis and whole genome sequencing. CA-CDI was defined as testing positive greater than 12 weeks following discharge or no previous hospital admission in conjunction with positive toxin stool testing.Results51.3% (40/78) of the patients in this study were found to have bona fide CA-CDI. The majority of patients were female (71.8% vs. 28.2%) with 50–59 years of age being most common (21.8%). Common co-morbidities included ulcerative colitis (1/40; 2.5%), Crohn’s disease (3/40; 7.5%), celiac disease (2/40; 5.0%) and irritable bowel syndrome (8/40; 20.0%). However, of 40 patients with CA-CDI, 9 (29.0%) had been hospitalized between 3 and 6 months prior and 31 (77.5%) between 6 and 12 months prior. The hypervirulent North American Pulostype (NAP) 1-like (9/40; 22.5%) strain was the most commonly identified pulsotype. Whole genome sequencing of CA-CDI isolates confirmed that NAP 1-like pulsotypes are commonplace in CA-CDI. From a therapeutic perspective, there was universal susceptibility to metronidazole and vancomycin.ConclusionsAll CA-CDI cases had some history of hospitalization if the definition were modified to health care facility exposure in the last 12 months and is supported by the genomic analysis. This raises the possibility that even CA-CDI may have nosocomial origins.

Aging impairs protective host defenses against Clostridioides (Clostridium) difficile infection in mice by suppressing neutrophil and IL-22 mediated immunity

BackgroundMorbidity and mortality associated with Clostridioides (formerly Clostridium) difficile infection (CDI) rises progressively with advanced age (≥65 years) due in part to perturbations of the gut microbiota and immune dysfunction. Epidemiological data of community-acquired CDI suggests increased susceptibility may begin earlier during middle-age (45–64 years) but the causation remains unknown. MethodsMiddle-aged (12–14 months) and young (2–4 months) adult mice were infected with C. difficile, and disease severity, gut microbiome and innate immune response were compared. Cytokine reconstitution studies were performed in infected middle-aged mice. ResultsInfection of middle-aged mice with C. difficile led to greater disease compared to young controls, which was associated with increases in C. difficile burden and toxin titers, and elevated bacterial translocation. With the exception of an expansion of C. difficile in middle-aged mice, microbiome analysis revealed no age-related differences. In contrast, middle-aged mice displayed a significant defect in neutrophil recruitment to the colon, with diminished levels of innate immune cytokines IL-6, IL-23 and IL-22. Importantly, recombinant IL-22 administration during CDI reduced morbidity and prevented death in middle-aged mice. ConclusionIncreased susceptibility to C. difficile occurs in middle-aged mice modeling the community-acquired CDI demographics and is driven by an impaired innate immune response.