Clostridium Difficile Research Articles

Fecal Microbiota, Live-jslm (RBL; REBYOTA™) for Recurrent Clostridioides difficile Infection

Clostridioides difficile infection (CDI) is one of the most common causes of health care–associated infections and is often precipitated by recent antibiotic use. CDI occurs after the healthy gut microbiota is disrupted and becomes dysbiotic. Standard-of-care antibiotics for CDI may perpetuate dysbiosis, fueling risk of recurrent CDI (rCDI). New therapeutic options for preventing rCDI include fecal microbiota, live-jslm (RBL), a US Food and Drug Administration–approved, single-dose, rectally administered, microbiota-based live biotherapeutic product. RBL, which is easily given by any health care professional, is hypothesized to assist in restoring dysbiosis and has proven efficacy, safety, and tolerability across diverse patient populations to prevent rCDI.

The Incidence of Diarrhea and Clostridium Difficile Colonization Due to Antibiotic Intake in Sample of Egyptian Pediatrics

The Incidence of Diarrhea and Clostridium Difficile Colonization Due to Antibiotic Intake in Sample of Egyptian Pediatrics

Mice colonized with the defined microbial community OMM19.1 are susceptible to Clostridioides difficile infection without prior antibiotic treatment.

Diverse gut microorganisms present in humans and mice are essential for the prevention of microbial pathogen colonization. However, antibiotic-induced dysbiosis of the gut microbiome reduces microbial diversity and allows Clostridioides difficile (C. difficile) to colonize the intestine. The Oligo-Mouse-Microbiota 19.1 (OMM19.1) is a synthetic community that consists of bacteria that are taxonomically and functionally designed to mimic the specific pathogen-free mouse gut microbiota. Here, we examined the susceptibility of OMM19.1 colonized mice to C. difficile infection (CDI) at a range of infectious doses (103, 105, and 107 spores) without prior antibiotic treatment. We found that mice colonized with OMM19.1 were susceptible to CDI regardless of the dose. The clinical scores increased with increasing C. difficile dosage. Infection with C. difficile was correlated with a significant increase in Ligilactobacillus murinus and Escherichia coli, while the relative abundance of Bacteroides caecimuris, Akkermansia muciniphila, Extibacter muris, and Turicimonas muris was significantly decreased following CDI. Our results demonstrate that the OMM19.1 community requires additional bacteria to enable C. difficile colonization resistance.IMPORTANCEThe human gut microbiota consists of a wide range of microorganisms whose composition and function vary according to their location and have a significant impact on health and disease. The ability to generate and test the defined microbiota within gnotobiotic animal models is essential for determining the mechanisms responsible for colonization resistance. The exact mechanism(s) by which healthy microbiota prevents Clostridioides difficile infection is unknown, although competition for nutrients, active antagonism, production of inhibitory metabolites (such as secondary bile acids), and microbial manipulation of the immune system are all thought to play a role. Here, we colonized germ-free C57BL/6 mice with a synthetic bacterial community (OMM19.1) that mimics the specific pathogen-free mouse microbiota. Following breeding, to enable immune system development, F1 mice were infected with three different doses of C. difficile. Our research suggests that there are additional essential microbial functions that are absent from the current OMM19.1 model.

Epidemiology of Clostridioides difficile PCR ribotype 181 after the COVID-19 pandemic in Northern Greece.

Clostridioides difficile infection (CDI) is one of the most significant causes of diarrhea in hospitalized patients. The aim of this study was to investigate the incidence and epidemiology of CDI after the COVID-19 pandemic in hospitalized patients in a rehabilitation center in Thessaloniki, Greece. Αretrospective observational cohort study was performed in inpatients diagnosed with diarrhea of all ages (January 2023 - December 2023) who were initially screened for CDI. From the total cohort of patients with proven CDI, some patients were randomly selected based on their monthly isolation incidence throughout the study period, to investigate their epidemiological data and clinical characteristics. Laboratory diagnosis of CDI was performed by enzyme immunoassay, followed by specific anaerobic culture and molecular testing for detection of toxigenic C. difficile. The isolated C. difficile strains were further characterized by PCR ribotyping. The annual incidence of CDI during the studyperiod was 27.1% (130/480). The linear trend of CDI incidence decreased from 32.5% to 18.2% (P= 0.024). The all-cause mortality rate was 5.0% (3/60). A positive correlation was observed between the length of hospital stay and the number of recurrences (r = 0.546, P < 0.001), while 28 patients (46.7%) experienced recurrence of the infection. Seven different PCR ribotypes were identified in thisstudy. C. difficile tcdA+, tcdB+, cdtA+, cdtB+ PCR ribotype 181 (RT181) was the predominant (76.6%, 46/60), followed by toxin A-negative PCR RT017 (11.6%, 7/60). The annual incidence of CDIdecreased after the COVID-19 pandemic. Our study demonstrates predominance of C. difficile RT181 with tcdA+, tcdB+, cdtA+, cdtB+ toxin gene profile after COVID-19 pandemic in Northern Greece.

Point Prevalence Survey of HAIs as a key component of Infection Prevention and Control programs

Abstract Healthcare-Associated Infections (HAIs) are a global concern, requiring surveillance strategies as Point Prevalence Surveys (PPS) to estimate their burden and investigate associated risk factors for targeted interventions in high-risk areas. This study aims to assess the prevalence of HAIs, identify determinants and evaluate antimicrobial use in a teaching hospital in Rome. A PPS was carried out from June 19th to 23rd, 2023, in accordance with the European Centre for Disease Prevention and Control (ECDC) protocol for HAIs and antimicrobial use in European acute care hospitals (version 6.1). Pearson’s chi-squared test was employed to investigate correlations between potential risk factors and HAIs. The survey included 829 patients with an average age of 56.3 years (SD: ±24.6). Of these, 48.4% were female and over half had visited the hospital’s Emergency Department (53.7%). The prevalence of active HAIs was 8.7%, with 72 patients diagnosed. Furthermore, 51.0% of all patients received at least one systemic antimicrobial agent, and 16.7% of those treated had an HAI. Penicillins (39.7%) and third-generation cephalosporins (37.8%) were the most frequently prescribed antimicrobials. The primary HAIs were bloodstream infections (34.1%), followed by urinary tract (27.3%), surgical site (23.9%), lower respiratory tract (6.8%), and gastrointestinal infections (7.9%). Escherichia coli (13.2%), Staphylococcus aureus (9.2%), and Clostridium difficile (6.6%) were the most frequently isolated pathogens. Intensive Care Unit admission, use of medical device, recent antibiotic therapy and prior hospitalization or surgery significantly correlated (p &amp;lt; 0.05) with increased HAIs risk. The detected prevalence of HAIs is lower than the national rates observed in 2022 (10.2%), which have increased since 2016. HAIs surveillance is essential for developing effective infection prevention and control programs and for optimizing resource allocation in hospital settings. Key messages • Surveillance of Healthcare-Associated Infections is crucial for developing targeted Infection Prevention and Control programs and optimizing hospital resource allocation. • Point Prevalence Surveys offer essential information for assessing the burden of Healthcare-Associated Infections and directing intervention strategies in hospitals.

Do the prevention procedures work in reducing infections?

Abstract Introduction Healthcare-associated infections (HCAIs) pose significant challenges in healthcare settings. Poor environmental hygiene contributes to HCAI. This study aims to evaluate and to assess the effectiveness of HCAI containment practices in nursing homes (NH). Methods The study examined infection prevention procedures in eight NHs supervised by the Multidisciplinary Commission of the Tuscany South-East Local Health Authority of Italy. Infection frequencies were obtained from NHs management and compliance with preventive procedures was assessed by inspection reports. Infection prevention protocols, including cleaning and disinfection procedures, were referenced from ministerial guidelines for hospital and territorial facilities. Comparisons was done whit Mann-Whitney test, using STATA. Results In 2023 more frequent infections were SARS-CoV-2 (19.5%), urinary tract infections (17%), pharyngitis (15.7%), influenza-like syndromes (ILI) (15%), and pneumonia (9%). Compared to 2022, significant improvements were observed in legionellosis surveillance, laundry, sanitary procedures, instrument disinfection, and hairdressing services. Non-compliance to specific procedures revealed differences in infectious onset like cleaning process verification with fungal infections (P = 0.01; M = 2,5), gastrointestinal infections (P = 0.04; M = 1.5); cleaning sanitary pans with Clostridium Difficile gastrointestinal infections (P = 0.04; M = 2); instrument disinfection with gastrointestinal infections (P = 0.04; M = 1.5) conjunctivitis (P = 0.01; M = 8); laundry procedures with pneumonia (P = 0.04; M = 18) and ILI (P = 0.04; M = 35). Conclusions These findings emphasize the importance of well-defined procedures in reducing HCAIs. While preventive measures demonstrate efficacy, continuous efforts are necessary for their consistent implementation. Continuous monitoring and stakeholder engagement are essential for developing sustainable strategies in preventing healthcare-associated infections. Key messages • Healthcare-associated infections are a significant complication in the healthcare sector and require effective practices in nursing homes. • Prevention measures are effective, but continuous and collaborative effort is needed to ensure their uniform implementation and develop more effective strategies in preventing HCAI.

Functional Nucleic Acids as Bacterial Biosensors: A Focus on Clostridioides difficile Infection

Clostridioides difficile (CD) is a Gram‐positive, anaerobic, and spore‐forming bacillus that colonizes the human gut and causes a range of diseases, such as pseudomembranous colitis and antibiotic‐associated diarrhea, that are generally known as CD infection (CDI). Rapid and accurate detection of CDI with high sensitivity and specificity is crucial for patient treatment, infection control, and epidemiological monitoring. Current diagnostic methods for CDI have several limitations, such as high cost, long turnaround time, suboptimal sensitivity, and the need for specialized equipment. Hence, novel detection methods that can overcome these limitations are needed. Functional nucleic acids (FNAs) are a promising class of molecular recognition element (MRE) that can be incorporated into biosensors for detecting infectious pathogens. Several FNAs have been developed for detecting CD. In this review, an overview of CD, CDI, and current diagnostic methods for CDI and their drawbacks are provided. Furthermore, the design principles and working mechanisms of FNAs as well as their applications for the detection of pathogenic bacteria, including CD, are discussed. The potential for developing point‐of‐care paper sensors using currently available CD‐selective FNAs is also highlighted.

Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation

Background Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI). Objectives To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI. Methods A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment. Results Patients with rCDI had poor HRQoL, which improved following FMT. Conclusions Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.

Genetic insight into the relationship between inflammatory bowel disease and Clostridioides difficile infection.

Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen. Conditional and joint multi-SNP analyses were used to identify independent associations. Imputation of the human leukocyte antigen (HLA) region with fine mapping was used to try to identify causal HLA allele groups. Two-sample bidirectional Mendelian randomization (MR) was implemented to determine causal relationships between IBD and CDI. A total of 3,500 cases of CDI and 674,323 controls were meta-analyzed, revealing one genome-wide significant variant for CDI, HLA-C;LINC02571-rs3134745-C (P = 4.27E-08), which annotated to the major histocompatibility complex on chromosome 6. While fine mapping did not identify a statistically significant HLA allele group, there was a suggestive signal for HLA-B*35:01 (P = 4.74e-04). Using two-sample MR, genetically predicted IBD was associated with increased risk of CDI (MR Egger [odds ratio {OR} 1.16, 95% confidence interval {CI} 1.02-1.31]). Subset analysis revealed that risk was primarily driven by genetically predicted ulcerative colitis (MR Egger [OR 1.22, 95% CI 1.05-1.41]). These results highlight the importance of the host immune response in CDI pathogenesis, help explain the observed relationship between IBD and CDI, and open new avenues for targeted treatment of CDI in IBD.IMPORTANCEData from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.

Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies

Infectious diseases in older adults present a significant challenge to the healthcare system, marked by increased morbidity, mortality, and rising costs of care. Age-related changes (ARCs) in the immune system, including immunosenescence and inflammaging, contribute to heightened susceptibility to severe infections and reduced vaccine responsiveness. Additionally, alterations in the normal microbial flora due to aging and factors such as antibiotic therapy predispose older individuals to infections and age-related diseases. Changes in body composition also affect the pharmacokinetics and pharmacodynamics of drugs, complicating the management of antibiotics and leading to potential overdoses, adverse drug reactions, or underdoses that foster antibiotic resistance. The inappropriate use of antibiotics has exacerbated the emergence of multidrug-resistant pathogens, posing a critical global concern. This narrative review provides an overview of immunosenescence and inflammaging and focuses on three major infectious diseases affecting older adults: bacterial pneumonia, urinary tract infections, and Clostridium difficile infections. Through this exploration, we aim to highlight the need for targeted approaches in managing infectious diseases in the aging population.

A case of Clostridium difficile infection as a complication of antibiotic therapy

This clinical case demonstrates the complexity of managing a comorbid patient with antibiotic-associated diarrhea. We observed a patient who, during therapy, developed extremely early premature birth with a live premature fetus (at 25-26 weeks), antibiotic-associated (Clostridium difficile) intractable diarrhea, pseudomembranous colitis, and acute dynamic intestinal obstruction. After treatment for 14 days, the patient’s condition improved.

Multicenter study on Clostridioides difficile infections in Mexico: exploring the landscape.

This study aims to outline Clostridioides difficile infection (CDI) trends and outcomes in Mexican healthcare facilities during the COVID-19 pandemic. Observational study of case series. Sixteen public hospitals and private academic healthcare institutions across eight states in Mexico from January 2016 to December 2022. CDI patients. Demographic, clinical, and laboratory data of CDI patients were obtained from clinical records. Cases were classified as community or healthcare-associated infections, with incidence rates calculated as cases per 10,000 patient days. Risk factors for 30-day all-cause mortality were analyzed by multivariate logistic regression. We identified 2,356 CDI cases: 2,118 (90%) were healthcare-associated, and 232 (10%) were community-associated. Common comorbidities included hypertension, diabetes, and cancer. Previous high use of proton-pump inhibitors, steroids, and antibiotics was observed. Recurrent infection occurred in 112 (5%) patients, and 30-day mortality in 371 (16%). Risk factors associated with death were a high Charlson score, prior use of steroids, concomitant use of antibiotics, leukopenia, leukocytosis, elevated serum creatine, hypoalbuminemia, septic shock or abdominal sepsis, and SARS-CoV-2 coinfection. The healthcare-associated CDI incidence remained stable at 4.78 cases per 10,000 patient days during the pre-and pandemic periods. However, the incidence was higher in public hospitals. Our study underscores the need for routine epidemiology surveillance and standardized CDI classification protocols in Mexican institutions. Though CDI rates in our country align with those in some European countries, disparities between public and private healthcare sectors emphasize the importance of targeted interventions.

Post-Discharge Outcomes of Elderly Patients Hospitalized for Inflammatory Bowel Disease Flare Complicated by Clostridioides difficile Infection.

Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short, intermediate, and long-term post-discharge complications among these patients. A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-months post-discharge IBD-related complication rates defined as: steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6-months and mortality at 12-months among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. In a cohort of 654 patients hospitalized for IBD (age 68.9 [interquartile range {IQR}]:63.9-75.2) years, 60.9% ulcerative colitis), 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6-months, and 12-months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs. 33.1%, p=0.8; 40.5% vs. 42.5%, p=0.66; and 4.6% vs. 8%, p=0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3-months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An ulcerative colitis diagnosis was the sole risk factor for complication at 6-months (aOR 1.5). CDI did not significantly impact outcomes or interact with IBD type. In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1-year.

Examining the impact of the COVID-19 pandemic on hospital-associated Clostridioides difficile infection.

To evaluate the impact of changes in the size and characteristics of the hospitalized patient population during the COVID-19 pandemic on the incidence of hospital-associated Clostridioides difficile infection (HA-CDI). Interrupted time-series analysis. A 576-bed academic medical center in Portland, Oregon. We established March 23, 2020 as our pandemic onset and included 24 pre-pandemic and 24 pandemic-era 30-day intervals. We built an autoregressive segmented regression model to evaluate immediate and gradual changes in HA-CDI rate during the pandemic while controlling for changes in known CDI risk factors. We observed 4.5 HA-CDI cases per 10,000 patient-days in the two years prior to the pandemic and 4.7 cases per 10,000 patient-days in the first two years of the pandemic. According to our adjusted segmented regression model, there were neither significant changes in HA-CDI rate at the onset of the pandemic (level-change coefficient = 0.70, P-value = 0.57) nor overtime during the pandemic (slope-change coefficient = 0.003, P-value = 0.97). We observed significant increases in frequency and intensity of antibiotic use, time at risk, comorbidities, and patient age before and after the pandemic onset. Frequency of C. difficile testing did not significantly change during the pandemic (P= 0.72). Despite large increases in several CDI risk factors, we did not observe the expected corresponding changes in HA-CDI rate during the first two years of the COVID-19 pandemic. We hypothesize that infection prevention measures responding to COVID-19 played a role in CDI prevention.

Gut Microbiota and New Microbiome-Targeted Drugs for Clostridioides difficile Infections.

Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice.

Treatment outcomes of mild to moderate Clostridioides difficile infection in inflammatory bowel disease: an Australian experience.

The incidence of Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) is rising and associated with adverse outcomes. Optimal treatment for CDI in IBD remains unknown, with various organisations suggesting vancomycin as first-line therapy. To compare treatment outcomes for metronidazole versus vancomycin in mild to moderate CDI in IBD. A retrospective analysis of IBD patients with CDI between January 2015 and December 2019 was conducted. Laboratory data and clinical outcomes were examined. Forty-seven discrete episodes of CDI in 34 patients occurred during the study period. Fifty-three per cent (18) had Crohn's disease, 44% (15) ulcerative colitis and 3% (1) IBD unclassified. Six per cent (3/47) of CDI cases were severe and excluded. In 68% (30/44) of mild to moderate CDI, metronidazole was prescribed, with treatment failure in 20% (6/30), CDI recurrence in 13% (4/30) and 20% (6/30) experiencing a further CDI episode. Comparatively, vancomycin was prescribed in 23% (10/44) without any treatment failures; however, 10% (1/10) had CDI recurrence and 40% (4/10) experienced another CDI episode. No statistically significant difference was noted between metronidazole and vancomycin therapy for treatment failure (P = 0.31), CDI recurrence (P = 1.0) or further CDI episodes (P = 0.23). Proton-pump inhibitor therapy was the only risk factor associated with a higher rate of the composite outcome and remained significant on multivariate logistic regression (odds ratio 12.99 (95% confidence interval = 1.21-139.97), P = 0.03). Metronidazole compared to vancomycin for treatment of mild to moderate CDI in IBD is effective however may be associated with higher rates of treatment failure.

Unveiling the impact of antibiotic stress on biofilm formation and expression of toxin-antitoxin system genes in Clostridium difficile clinical isolates.

The study investigates how antibiotics affect biofilm formation and toxin gene expression in Clostridium difficile, which is essential for its survival and persistence. The study confirmed 25 strains of C. difficile and assessed biofilm formation. The MIC of metronidazole and vancomycin was determined through agar dilution, and the impact of sub-MIC levels on biofilm formation and eradication was investigated. Additionally, Real-time PCR was used to analyze the expression levels of target genes related to antibiotic treatment. We found that certain genes, such as the ImmA/IrrE system, were associated with increased biofilm formation in isolates. Sub-MIC antibiotic levels influenced gene expression related to biofilm activities, particularly emphasizing the importance of toxin-antitoxin systems. The results suggest that antibiotics at sub-MIC levels may play a signaling role in promoting biofilm formation and gene expression in C. difficile. Our study suggests that toxin and antitoxin genes may impact C. difficile biofilm formation, while antibiotics could signal biofilm strengthening and gene expression increase.

Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials

Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials

Validation of electronic health record data to identify hospital-associated Clostridioides difficile infections for retrospective research.

Clostridioides difficile infection (CDI) research relies upon accurate identification of cases when using electronic health record (EHR) data. We developed and validated a multi-component algorithm to identify hospital-associated CDI using EHR data and determined that the tandem of CDI-specific treatment and laboratory testing has 97% accuracy in identifying HA-CDI cases.

Efficacy of grapefruit seed extract and lactic acid bacteria in reducing Clostridioides difficile infection via gut microbiota modulation

Antibiotic-induced dysbiosis is a key factor that causes Clostridioides difficile infection (CDI). The current first-line drugs for initial CDI are antibiotics, and finding an alternate therapy to prevent recurrent CDI is essential. In this study, the anti-C. difficile activities of two isolated probiotic strains (Pediococcus pentosaceus CD5 and Lactobacillus salivarius CD4) and grapefruit seed extract (GSE) were investigated in vitro and in vivo. Specifically, GSE inhibited the growth of C. difficile at a minimal inhibitory concentration (MIC) of 40 ppm. Similarly, live cells of the two probiotics, as well as their cell-free culture supernatants, with or without pH adjustment, substantially suppressed C. difficile growth. In a CDI mouse model, C. difficile colonization in the cecum and colon inflammation were significantly reduced by GSE, followed by the probiotic treatments. A metagenomic analysis of cecal feces revealed that GSE and probiotic treatments modulated gut microbial compositions and enhanced the relative abundances of butyrate-producing bacteria. Therefore, GSE and the novel probiotics can potentially be administered as alternative therapies to alleviate CDI by modifying the gut microbiota.