Cause Of Healthcare-associated Diarrhea Research Articles

A retrospective budget impact analysis of fidaxomicin treatment for Clostridioides difficile infections (CDI) in Germany

ABSTRACT Background Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Research suggests that treating C. difficile infections (CDI) with fidaxomicin (FDX) is more effective than vancomycin (VAN), with potential cost savings. The objective was to calculate the budget impact of FDX treatment compared to VAN from a German payer perspective. Research design and methods The analysis used real-world data of patients discharged from University Hospital Cologne between Jan-01–2018 and Dec-31–2019. We identified recurrent and non-recurrent CDI cases and calculated direct treatment costs based on G-DRG flat rates. To calculate average costs per treatment and the budget impact, recurrence probabilities for VAN and FDX were taken from published evidence (28-day and 90-day scenarios). Results Totally, 475 cases were analyzed, thereof 421 non-recurrent, causing mean costs of €32,901 per case (95% CI: 27.752–38.050). Thirty-two patients experienced a recurrence within 28 days, yielding mean costs of €10,952 (95% CI: 5.627–16.277) for their additional hospital stay. The resulting budget impact was €1,303 (95% CI: 670–1.937) in favor of FDX, ranging from €148.34 to €2,190.30 in scenario analyses. Conclusion The analysis indicates FDX treatment can lead to cost savings compared to VAN. Future research should focus on specific patient groups, such as refractory CDI patients.

Comparison of rectal swabs and fecal samples for the detection of Clostridioides difficile infections with a new in-house PCR assay.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of C. difficile.

Identification of Clostridioides difficile mutants with increased daptomycin resistance.

C. difficile is the leading cause of healthcare-associated diarrhea and is a threat to public health due to the risk of recurrent infections. Understanding biosynthesis of the atypical cell envelope of C. difficile may provide insight into novel drug targets to selectively inhibit C. difficile. Here, we identified mutations that increased daptomycin resistance and allowed us to better understand phospholipid synthesis, cell envelope biogenesis, and stress response in C. difficile.

Genomic surveillance of Clostridioides difficile transmission and virulence in a healthcare setting.

Clostridioides difficile infection remains a leading cause of hospital-associated diarrhea, despite increased antibiotic stewardship and transmission prevention strategies. This suggests a changing genomic landscape of C. difficile. Our study provides insight into the nature of prevalent C. difficile strains in a hospital setting and transmission patterns among carriers. Longitudinal sampling of surfaces and patient stool revealed that both toxigenic and nontoxigenic strains of C. difficile clade 1 dominate these two wards. Moreover, quantification of transmission in carriers of these clade 1 isolates underscores the need to revisit infection prevention measures in this patient group. We identified unique genetic signatures associated with virulence in this clade. Our data highlight the complexities of preventing transmission of this pathogen in a hospital setting and the need to investigate the mechanisms of in vivo persistence and virulence of prevalent lineages in the host gut microbiome.

Clostridioides difficile Infection: Diagnosis and Treatment Challenges.

Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

Using whole genome sequencing to characterize Clostridioides difficile isolates at a tertiary center in Melbourne, Australia.

Clostridioides difficile infection (CDI) is the commonest cause of healthcare-associated diarrhea and undergoes standardized surveillance and mandatory reporting in most Australian states and territories. Historically attributed to nosocomial spread, local and international whole genome sequencing (WGS) data suggest varied sources of acquisition. This study describes C. difficile genotypes isolated at a tertiary center in Melbourne, Australia, their likely source of acquisition, and common risk factors. Retrospective observational study. The Royal Melbourne Hospital (RMH), a 570-bed tertiary center in Victoria, Australia. Short-read whole genome sequencing was performed on 75 out of 137 C. difficile isolates obtained from 1/5/2021 to 28/2/2022 and compared to previous data from 8/11/2015 to 1/11/2016. Existing data from infection control surveillance and electronic medical records were used for epidemiological and risk factor analysis. Eighty-five (62.1%) of the 137 cases were defined as healthcare-associated from epidemiological data. On genome sequencing, 33 different multi-locus sequence type (MLST) subtypes were identified, with changes in population structure compared to the 2015-16 period. Risk factors for CDI were present in 130 (94.9%) cases, including 108 (78.8%) on antibiotics, 86 (62.8%) on acid suppression therapy, and 25 (18.2) on chemotherapy. In both study periods, most C. difficile isolates were not closely related, suggesting varied sources of acquisition and that spread of C. difficile within the hospital was unlikely. Current infection control precautions may therefore warrant review. Underlying risk factors for CDI were common and may contribute to the proportion of healthcare-associated infections in the absence of proven hospital transmission.

Clostridiumdifficile infection in pediatric patients (Review).

Clostridium difficile (C. difficile) infection (CDI) is the most common cause of healthcare-associated diarrhea and among adults, the worldwide incidence rate of the infection is increasing. There is a small amount of data in the literature for pediatric patients, but most indicate an increasing trend. C. difficile is a constituent of the normal microbiota; however, under specific conditions that cause a disruption of the normal bacterial flora, colonization of C. difficile and the released toxins that cause inflammation and mucosal damage occurs. Risk factors for CDI at any age include hospitalization, exposure to antibiotics, administration of proton pump inhibitors, invasive mechanical ventilation, immunosuppression and presence of associated comorbidities. Clinical manifestations range from asymptomatic colonization to fulminant disease characterized by toxic megacolon, intestinal perforation and, rarely, death. The aim of the present review was to outline the features of CDI in pediatric patients.

Role of probiotics in preventing Clostridioides difficile infection in older adults: an integrative review.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. This infection can particularly affect older adults, the most susceptible to CDI. Currently, the standard therapeutic measure is antibiotic therapy, which in turn increases the risk of recurrence of the infection by its collateral damage to the patient's microbiota. Probiotics are live microorganisms capable of maintaining balance in the intestinal microbiota. This study aims to perform an integrative review of the protective benefit of probiotics in CDI and diarrhea associated with C. difficile. The PubMed, Scopus, and Web of Science databases, the 10-year time cutoff, and the Prism Flow diagram were used for data collection. We observed no consensus among the studies; however, three of the seven evaluated studies demonstrated that the use of probiotics in older adults could contribute to reducing the incidence of hospital-onset CDI. We also found that the studies evaluated a wide variety of microorganisms, particularly Saccharomyces boulardii, associated with beneficial effects. More research is needed to understand the successful use of probiotics in the prevention of CDI in hospitalized older adults receiving antibiotics.

The influence of exposure to various concentrations of five antimicrobial agents on intracellular cytotoxin B production in <i>Clostridioides difficile</i>

Background: Clostridioides difficile is an important cause of healthcare-associated diarrhea. Several anti- microbial agents are known to promote C. difficile infection (CDI). The impact of various concentrations of ampicillin (AMP), cefotaxime (CTX), clindamycin (CC), metronidazole (MTZ) and vancomycin (VAN) on intra-cellular cytotoxin B production was investigated in this study.
 Methodology: Six clinical strains of C. difficile were grown at minimum inhibitory concentration (MIC) and sub-MIC concentrations of these antibiotics. Inoculum standardization was performed by Miles and Misra method. Intracellular toxin B production was detected using Vero cell cytotoxicity assay in sonicated cultures on days 1, 2, 3, 4, 5 and 7 days of incubation.
 Results: There was a heterogeneous relationship between antibiotic exposure and the intra-cellular toxin production by the toxigenic strains. Clinical strains of C. difficile when exposed to MIC and sub-inhibitory concentrations of certain antibiotics produced high cytotoxin levels. All toxigenic isolates produced increased levels of cell-bound cytotoxin after exposure to antibiotics but there was no consistent pattern and the response to different doses varied considerably. Metronidazole was the most potent inducer of cell-bound cytotoxin followed by cefotaxime and clindamycin. Vancomycin induced the least amount of cytotoxin activity.
 Conclusion: The effects of sub-inhibitory concentration of antibiotic that predispose to C. difficile infection may partially suppress the normal gut flora, allowing colonization and growth of C. difficile, and may affect the level of toxin produced.

Global research on Clostridium difficile-associated diarrhoea: A visualized study.

BACKGROUND Clostridioides (Clostridium) difficile (C. difficile) is still the most common cause of healthcare-associated diarrhoea and is increasing in prevalence as a community-acquired infection. In addition, the emergence of antibiotic resistance in C. difficile can increase the likelihood of the disease developing and/or spreading.AIMTo provide an up-to-date picture of the trends in publications related to C. difficile infection, together with specific insights into hot-button issues in this field. METHODSPublications on C. difficile infections in the field of microbiology between 2001 and 2020 were identified from the Scopus database and Reference Citation Analysis. Bibliometric indicators were determined, including the number and type of publications, countries, affiliations, funding agencies, journals and citation patterns. VOSviewer was used to determine research areas and hot-button issues by identifying recurring terms with a high relative occurrence in the title and abstract.RESULTSA total of 8127 documents on ‘C. difficile-associated diarrhoea’ published between 2001 and 2020 were retrieved from the Scopus database. In the last decade, there has been a significant almost fourfold increase in the number of published papers on this topic. The United States was among the countries (44.11%) with the most publications, and the most involved institution was the University of Leeds in the United Kingdom (2.50%). Three clusters of research were identified and included ‘illness spectrum and severity, as well as the signs, symptoms and clinical pathogenesis of C. difficile’; ‘laboratory diagnosis and characterization of C. difficile’ and ‘risk factors for C. difficile infection’.CONCLUSIONThis study contains the most up-to-date and comprehensive data ever compiled in this field. More international research and cross-institutional collaborations are needed to address more global C. difficile concerns and to benefit from greater sharing of expertise, which will result in higher quality or more effective studies in the future. Promising research avenues in the near future may draw the attention of relevant scientists and funding organizations and open up novel C. difficile infection–based diagnosis and treatment approaches.

Treatment and Outcomes of Clostridioides difficile Infection in Switzerland: A Two-Center Retrospective Cohort Study.

Objectives: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, often complicated by severe infection and recurrence with increased morbidity and mortality. Data from large cohorts in Switzerland are scarce. We aimed to describe diagnostic assays, treatment, outcomes, and risk factors for CDI in a large cohort of patients in Switzerland. Methods: We conducted a retrospective cohort study of CDI episodes diagnosed in patients from two tertiary care hospitals in Switzerland. During a 3-month follow-up, we used a composite outcome combining clinical cure at day 10, recurrence at week 8, or death, to evaluate a patient’s response. Unfavorable outcomes consisted in the occurrence of any of these events. Results: From January 2014 to December 2018, we included 826 hospitalized patients with documented CDI. Overall, 299 patients (36.2%) had a severe infection. Metronidazole was used in 566 patients (83.7%), compared to 82 patients (12.1%) treated with vancomycin and 28 patients (4.1%) treated with fidaxomicin. Overall mortality at week 8 was at 15.3% (112/733). Eighty-six patients (12.7%) presented with clinical failure at day 10, and 78 (14.9%) presented with recurrence within 8 weeks; 269 (39.8%) met the composite outcome of death, clinical failure, or recurrence. The Charlson Comorbidity Index score (p < 0.001), leukocytes > 15 G/L (p = 0.008), and the use of metronidazole (p = 0.012) or vancomycin (p = 0.049) were factors associated with the composite outcome. Conclusions: Our study provides valuable insights on CDI treatment and outcomes in Switzerland, highlights the heterogeneity in practices among centers, and underlines the need for the active monitoring of clinical practices and their impact on clinical outcomes through large multicentric cohorts.

Characteristics of antibiotic exposures for surgical procedures prior to Clostridioides difficile diagnosis—Minnesota, 2018

Background:Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. Significant risk factors for CDI include antibiotic use and healthcare exposure. Antibiotics are often administered before, during and/or after surgery to prevent postsurgical infection. The contribution of surgery-related antibiotics to the overall CDI burden has not been well described, and assessment of the appropriateness of surgical antibiotic use is complicated by complex clinical guidelines. We have described surgical antibiotic prophylaxis history among adult with CDI in Minnesota in 2018. Method: The Minnesota Department of Health (MDH) performs 5-county active population- and laboratory-based CDI surveillance as a CDC Emerging Infections Program site. Incident CDI was defined as stool positive for C. difficile by toxin or molecular assay from a person aged ≥18 years with no positive test in the preceding 8 weeks. History of CDI was defined as having had a previous CDI episode in the 2009–2018 surveillance data set. Medical records were reviewed for 12 weeks prior to incident CDI test date to identify antibiotic prescriptions. Antibiotics with documented indication for surgical-site infection prevention or surgical prophylaxis were classified as “surgical antibiotic prophylaxis” (SPPX). SPPX type (eg, intraoperative, postoperative), appropriateness of SPPX, and clinical guideline adherence were not assessed. Results: During 2018, 812 incident CDIs were reported to MDH among 736 patients. SPPX preceded 84 (10.3%) cases, non-SPPX antibiotic use preceded 465 cases (57.3%), and 263 cases (32.4%) had no documented prior antibiotic use. The median age of incident CDIs with preceding SPPX was 68 years (IQR, 54–79.5). In 25 incident CDI cases with preceding SPPX (29.8%), there were no other antibiotic exposures. Among incident CDIs with preceding SPPX, 11 (13.1%) had &gt;1 surgery event with SPPX. Prior CDI was identified for 13 (15.7%) with SPPX. Among 99 procedures with preceding SPPX, orthopedic surgeries (n = 27, 27.3%), gastrointestinal surgeries (n = 26, 26.3%), and cardiovascular surgeries (n = 22, 22.2%) were most common. In total 18 SPPX prescriptions (18.2%) originated in outpatient settings. SPPX drugs included cefazolin (n = 67, 67.7%), ceftriaxone (n = 7, 7.1%), ertapenem (n = 6, 6.1%), and clindamycin (n = 6, 6.1%). Median SPPX duration was 1 day (IQR, 1–2), and the median number days between surgery and specimen collection date was 19 (IQR, 7–49). Conclusions: Antibiotic stewardship programs should assess surgical prescribing, including in outpatient centers. Even short antibiotic duration for surgery could put patients at risk for CDI. More data are needed to evaluate the appropriateness of SPPX prescribing and to describe the impact of SPPX on CDI.Funding: NoneDisclosures: None

Epidemiology of Clostridioides difficile Infection in Portugal: A Retrospective, Observational Study of Hospitalized Patients.

Clostridioides difficile is the main cause of healthcare-associated diarrhea in Europe and North America. The aim of this study was to characterize the epidemiology and clinical burden of Clostridioides difficile infection among hospitalized patients in Portugal. Retrospective study conducted in six public hospital centers in Portugal. All primary Clostridioides difficile infection episodes and related recurrences occurring in 2017, as well as episodes developing two to eight weeks after the last episode diagnosed in that year, were documented. The National Reference Laboratory (National Institute of Health Dr. Ricardo Jorge) provided national surveillance data on Clostridioides difficile infection. A total of 385 inpatients with at least one primary episode diagnosed in 2017 were included. Most patients were aged over 70 years-old (73.2%). The included patients developed 451 episodes during the observation period. Approximately 44% of primary episodes were community-associated. Most episodes (94.9%) occurred in patients with one or more risk factors, with recent antibiotic exposure being particularly common (86.0%). All-cause in-hospital mortality was 19.5%, being significantly higher in patients aged over 65 years-old versus those aged 18 to 64 years-old (22.4% vs 7.8%, respectively). Over 50 different ribotypes were observed among 206 Clostridioides difficile strains received by the National Reference Laboratory. In Portugal, hospitalized patients with Clostridioides difficile infection are mostly older patients presenting risk factors for the development of this infection, particularly recent antibiotic exposure. Mortality is disproportionately high among the older population. Community-associated Clostridioides difficile infection is common among inpatients with this infection.

Whole-Genome Sequencing Reveals the High Nosocomial Transmission and Antimicrobial Resistance of Clostridioides difficile in a Single Center in China, a Four-Year Retrospective Study.

ABSTRACTClostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China.IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.

Rate and predictors of 30-day readmission for clostridiodes difficile: a United States analysis

Background Clostridiodes difficile is a leading cause of healthcare-associated diarrhea. In this study, we aimed to identify the rates and predictors for 30-day readmissions of Clostridiodes difficile Enterocolitis (CDE) in the United States. Methods We conducted a retrospective study of the Nationwide Readmissions Database to identify adult hospitalizations with a principal diagnosis of CDE for 2018. Individuals <18 years old and elective hospitalizations were excluded. Primary outcomes included readmission rate and the top ten principal diagnosis on readmission, while the secondary outcomes were inpatient mortality, hospital costs and independent predictors of 30-day all-cause readmissions. Furthermore, we devised a scoring system to estimate the risk of CDE readmissions. Stata® Version 16 was used for statistical analysis and p-values ≤0.05 were statistically significant. Results We identified 94,668 index hospitalizations and 18,296 readmissions at 30-days for CDE in 2018. The 30-day all-cause readmission rate was 25.7%. On readmission, CDE was the most common principal diagnosis (25.7%), followed by unspecified sepsis, and acute renal failure. A female predominance was also noted for index and 30-day readmissions of CDE. Compared to index admissions, we noted higher odds of inpatient mortality [4.4 vs 1.4%, Odds Ratio (OR):3.32, 95% Confidence Interval (CI):2.87–3.84, p < 0.001], longer mean length of stay (LOS) [6.4 vs 5.6 days, Mean Difference (MD):0.9, 95% CI:0.7–1.0, p < 0.001), and higher mean total hospital charge (THC) [$56,015 vs $40,871, MD:15,144, 95% CI:13,260–17,027, p < 0.001] for 30-day readmissions of CDE. Independent predictors for 30-day all-cause readmissions of CDE included discharged against medical advice (AMA) [Adjusd Hazard Ratio (aHR):2.01, 95% CI:1.73–2.53, p < 0.001], diabetes mellitus (DM) [aHR:1.22, 95% CI:1.16–1.29, p < 0.001], and chronic kidney disease (CKD) [aHR:1.29, 95% CI:1.21–1.37, p < 0.001]. Conclusion The all-cause 30-day readmission rate and inpatient mortality for CDE was 25.7% and 4.4%, respectively. Discharge AMA, DM and CKD were independent predictors for 30-day all-cause readmissions of CDE. KEY MESSAGE The 30-day all-cause readmission rate for Clostridiodes difficile Enterocolitis was noted to be 21.4% in 2018. Independent predictors of 30-day all-cause readmissions for Clostridiodes difficile Enterocolitis include diabetes mellitus, discharged against medical advice and chronic kidney disease. Readmissions of Clostridiodes difficile Enterocolitis had higher mortality rates, healthcare cost and length of hospital stay compared to index admissions.

Prediction of in-hospital mortality of Clostriodiodes difficile infection using critical care database: a big data-driven, machine learning approach

Research objectivesClostriodiodes difficile infection (CDI) is a major cause of healthcare-associated diarrhoea with high mortality. There is a lack of validated predictors for severe outcomes in CDI. The aim of...

Milk Exosomes Protect Human Microbiota Associated-Mice Against Clostridioides difficile Infection

ObjectivesExosomes are natural nanoparticles that facilitate cell-to-cell communication in animals and bacteria. Milk contains ∼1012 exosomes/mL. Evidence suggests that milk exosomes (MEs) contribute to maintaining a tight gut barrier function, bind toxins secreted by gut pathogens, and alter the growth of gut bacteria. Clostridioides difficile infection is a leading cause of health care-associated diarrhea in North America. Our objective of this study is to test if milk exosomes alter the severity of C. difficile infection. MethodsC57BL/6 mice stably colonized with a gut microbiome from a healthy elderly human (HMAmice) were fed ME- and RNA-sufficient (ERS) diet or ME- and RNA-depleted (ERD) diet for four weeks starting at age of three weeks (N = 20 in ERS, 17 in ERD). The content of ME and miRNA cargos in ERD is 15% and 1% of that in ERS. After four weeks, mice were treated with a combination of six antibiotics and challenged with 105C. difficile spores. Disease progression was monitored over time through measurement of weight loss, changes in behavior and stool consistency, and mortality. C. difficile colonization and toxin activity over time were assessed by colony forming units (CFU) and relative toxin units (RTU) in feces. A subset of mice was euthanized on day 3 to collect tissue samples for measurement of tissue damage and inflammation. Mann-Whitney test was used for statistical analysis and P < 0.05 was considered statistically significant. ResultsMice fed ERD diet exhibited more severe disease than mice fed ERS diet. Mice fed ERD diet had an increased mortality rate (58%) compared to mice fed ERS diet (25%, P = 0.0481) as well as 3-fold increase in weight loss two days following C. difficile infection compared to mice on an ERS diet (3.07 ± 3.77% (ERD) vs 1.08 ± 5.92%, P = 0.0488), The level of CFU and toxin activity was also higher in ERD-fed mice than that in ERS-fed mice. Finally, myeloperoxidase (MPO) activity assays (marker of neutrophil infiltration) and IL17a qRT-PCR provided evidence of higher immune activation in ERD-fed mice compared to ERS-fed mice. ConclusionsMEs decreased the severity of C. difficile infection in juvenile HMAmice. Funding SourcesNIH P20GM104320, NIFA 2016-67001-25301 and 2020-67017-30834, USDA W-4002.

A significant decreased in the frequency of Clostridioides difficile infection at the Italian Hospital of Desio over the last decade

Clostridiodes difficile infection (CDI) is the most important cause of healthcare-associated diarrhea. The decreasing trend of CDI from 15% to 4% observed at the Italian Hospital of Desio over a 10-year period is due to prevention strategies. Our data highlight the importance of surveillance studies to control CDI.

Global Landscape of Clostridioides Difficile Phylogeography, Antibiotic Susceptibility, and Toxin Polymorphisms by Post-Hoc Whole-Genome Sequencing from the MODIFY I/II Studies.

IntroductionClostridioides (Clostridium) difficile infection, the leading cause of healthcare-associated diarrhea, represents a significant burden on global healthcare systems. Despite being a global issue, information on C. difficile from a global perspective is lacking. The aim of this study is to model the global phylogeography of clinical C. difficile.MethodsUsing samples collected from the MODIFY I and II studies (NCT01241552, NCT01513239), we performed whole-genome sequencing of 1501 clinical isolates including 37 novel sequence types (STs), representing the largest worldwide collection to date.ResultsOur data showed ribotypes, multi-locus sequence typing clades, and whole-genome phylogeny were in good accordance. The clinical C. difficile genome was found to be more conserved than previously reported (61% core genes), and modest recombination rates of 1.4–5.0 were observed across clades. We observed a significant continent distribution preference among five C. difficile clades (Benjamini-Hochberg corrected Fisher’s exact test P < 0.01); moreover, weak association between geographic and genetic distance among ribotypes suggested sources beyond healthcare-related transmission. Markedly different trends of antibiotic susceptibility among lineages and regions were identified, and three novel mutations (in pyridoxamine 5′-phosphate oxidase family protein: Tyr130Ser, Tyr130Cys, and a promoter SNP) associated with metronidazole-reduced susceptibility were discovered on a nim-related gene and its promotor by genome-wide association study. Toxin gene polymorphisms were shown to vary within and between prevalent ribotypes, and novel severe mutations were found on the tcdC toxin regulator protein.ConclusionOur systematic characterization of a global set of clinical trial C. difficile isolates from infected individuals demonstrated the complexity of the genetic makeup of this pathogenic organism. The geographic variability of clades, variability in toxin genes, and mutations associated with antibiotic susceptibility indicate a highly complex interaction of C. difficile between host and environment. This dataset will provide a useful resource for validation of findings and future research of C. difficile.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00426-6.

Fecal host biomarkers predicting severity of Clostridioides difficile infection.

Clostridioides difficile is a major cause of health care–associated diarrhea. Severity ranges from mild to life-threatening, but this variability remains poorly understood. Microbiologic diagnosis of C. difficile infection (CDI) is straightforward but offers little insight into the patient’s prognosis or into pathophysiologic determinants of clinical trajectory. The aim of this study was to discover host-derived, CDI-specific fecal biomarkers involved in disease severity. Subjects without and with CDI diarrhea were recruited. CDI severity was based on Infectious Diseases Society of America/Society for Healthcare Epidemiology of America criteria. We developed a liquid chromatography tandem mass spectrometry approach to identify host-derived protein biomarkers from stool and applied it to diagnostic samples for cohort-wise comparison (CDI-negative vs. nonsevere CDI vs. severe CDI). Selected biomarkers were orthogonally confirmed and subsequently verified in a CDI mouse model. We identified a protein signature from stool, consisting of alpha-2-macroglobulin (A2MG), matrix metalloproteinase-7 (MMP-7), and alpha-1-antitrypsin (A1AT), that not only discriminates CDI-positive samples from non-CDI ones but also is potentially associated with disease severity. In the mouse model, this signature with the murine homologs of the corresponding proteins was also identified. A2MG, MMP-7, and A1AT serve as biomarkers in patients with CDI and define novel components of the host response that may determine disease severity.