Epidemiology Of Clostridioides Difficile Infection Research Articles

Clostridioides difficile infections caused by hypervirulent strains: a single-centre real-life study.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infections worldwide, with hypervirulent strains linked to severe disease and higher mortality. This study aims to analyze the epidemiology of CDI at a tertiary-care hospital in Italy and compare clinical outcomes between patients infected with hypervirulent and non-hypervirulent strains. A retrospective comparative study was conducted on patients diagnosed with CDI at ASST Spedali Civili di Brescia, Italy, from January 2015 to June 2023. Hypervirulent strains were identified using the GeneXpert assay as positive for cytotoxin gene (tcdB), binary toxin genes (tcdA and tcdB) and a single nucleotide deletion at position 117 in the tcdC gene and compared to a randomized matched control group with non-hypervirulent CDI. Clinical data were collected and analyzed, with multivariate logistic regression employed to identify risk factors for hypervirulent CDI. Of 1,059 positive C. difficile specimens, a statistically significant trend between January 2015 to June 2023 was found in the increasing incidence of CDI cases per 1,000 hospital admissions and 10,000 bed-days. Notably, a remarkable increase of hypervirulent strains was recorded in 2021 and 2022 when compared to previous years. A total of 130 patients were analyzed: 62 (47.7%) with hypervirulent CDI and 68 (52.3%) controls. Hypervirulent CDI was associated with higher 30-day mortality (18% vs. 5.8%, p = 0.03). Multivariate analysis showed that hypervirulent CDI significantly increased 30-day mortality risk (OR = 9.915, CI = 2.37-61.05, p = 0.005) and that prior antibiotic therapy was a significant risk factor (OR = 5.49, CI = 1.19-39.96, p = 0.047). Our epidemiological data, while suggesting a potential resurgence in CDI transmission during COVID-19 pandemic, are derived from a single-center experience with limited generalizability to the broader population. Nonetheless, they highlight the need for strengthened antimicrobial stewardship and national surveillance systems to effectively monitor and manage these strains.

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.

Microbiota restoration for recurrent Clostridioides difficile infection.

Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.

Best Practices in the Management of Clostridioides difficile Infection in Developing Nations.

Clostridioides difficile infection (CDI) is a well-known cause of hospital-acquired infectious diarrhea in developed countries, though it has not been a top priority in the healthcare policies of developing countries. In the last decade, several studies have reported a wide range of CDI rates between 1.3% and 96% in developing nations, raising the concern that this could represent a healthcare threat for these nations. This review defines developing countries as those with a human development index (HDI) below 0.8. We aim to report the available literature on CDI epidemiology, diagnostics, management, and prevention in developing countries. We identify limitations for CDI diagnosis and management, such as limited access to CDI tests and unavailable oral vancomycin formulation, and identify opportunities to enhance CDI care, such as increased molecular test capabilities and creative solutions for CDI. We also discuss infection prevention strategies, including antimicrobial stewardship programs and opportunities emerging from the COVID-19 pandemic, which could impact CDI care.

Epidemiology of Clostridioides difficile infection at one hospital 10 years after an outbreak of the epidemic C. difficile strain BI/027: changing strain prevalence, antimicrobial susceptibilities, and patient antibiotic exposures.

In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of Clostridioides difficile isolates recovered from first-episode C. difficile infection (CDI) cases, BI represented 19% of first-episode CDI isolates in 2013-2015. Two additional REA group strains accounted for 31% of isolates (Y, 16%; DH, 12%). High-level resistance to fluoroquinolones and azithromycin was more common among BI isolates than among DH, Y, and non-BI/DH/Y isolates. Multivariable analysis revealed that BI cases were 2.47 times more likely to be associated with fluoroquinolone exposure compared to non-BI cases (95% confidence interval [CI]: 1.12-5.46). In addition, the odds of developing a CDI after third- or fourth-generation cephalosporin exposure was 2.83 times for DH cases than for non-DH cases (95% CI: 1.06-7.54). Fluoroquinolone use in the hospital decreased from 2005 to 2015 from a peak of 113 to a low of 56 antimicrobial days/1,000 patient days. In contrast, cephalosporin use increased from 42 to 81 antimicrobial days/1,000 patient days. These changes correlated with a decrease in geometric mean MIC for ciprofloxacin (61.03 to 42.65 mg/L, P = 0.02) and an increase in geometric mean MIC for ceftriaxone (40.87 to 86.14 mg/L, P < 0.01) among BI isolates. The BI strain remained resistant to fluoroquinolones, but an overall decrease in fluoroquinolone use and increase in cephalosporin use were associated with a decrease in the prevalence of BI, an increased diversity of C. difficile strain types, and the emergence of strains DH and Y.

Clostridioides difficile infection epidemiology during the COVID-19 pandemic in Greece.

Aim: The aim was to highlight the incidence and epidemiology of C. difficile infections (CDI) in a tertiary Greek hospital during the COVID-19 pandemic.Methods: A single-center prospective observational cohort study was conducted (October 2021 until April 2022). 125 C. difficile isolates were cultured from hospitalized patients stool samples and screened by PCR for toxin A (tcdA), toxin B (tcdB), binary toxin (cdtA and cdtB) genes and the regulating gene of tcdC.Results: The incidence of CDI increased to 13.1 infections per 10,000bed days. The most common PCR ribotypes identified included hypervirulent RT027-related RT181 (73.6%), presumably hypervirulent RT126 (8.0%) and toxin A negative RT017 (7.2%).Conclusion: Although the incidence of CDI increased significantly, the CDI epidemiology remained stable.

Genetic determinants of resistance to antimicrobial therapeutics are rare in publicly available Clostridioides difficile genome sequences.

To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. The frequency of mutations causing reduced susceptibility to vancomycin and metronidazole, respectively, increased strongly after 2000, peaking at up to 52% of all sequenced C. difficile genomes. However, both mutations declined sharply more recently, reflecting major changes in CDI epidemiology. We detected mutations associated with fidaxomicin resistance in several major genotypes, but found no evidence of international spread of resistant clones. The pCD-METRO plasmid, conferring metronidazole resistance, was detected in a single previously unreported C. difficile isolate, recovered from a hospital patient in Germany in 2008. The pX18-498 plasmid, putatively associated with decreased vancomycin susceptibility, was confined to related, recent isolates from the USA. Phenotype measurements confirmed that most of those genetic features were useful predictors of antibiotic susceptibility, even though ranges of MICs typically overlapped among isolates with and without specific mutations. Genomic data suggested that resistance to therapeutic antimicrobial drugs is rare in C. difficile. Public antimicrobial resistance marker databases were not equipped to detect most of the genetic determinants relevant to antibiotic therapy of CDI.

The changing epidemiology of Clostridioides difficile infection and the NAP1/027 strain in two Québec hospitals: a 17-year time-series study.

To describe the epidemiology of healthcare-associated Clostridioides difficile infection (HA-CDI) in two Québec hospitals in Canada following the 2003 epidemic and to evaluate the impact of antibiotic stewardship on the incidence of HA-CDI and the NAP1/027 strain. Time-series analysis. Two Canadian tertiary care hospitals based in Montréal, Québec. Patients with a positive assay for toxigenic C. difficile were identified through infection control surveillance. All cases of HA-CDI, defined as symptoms occurring after 72 hours of hospital admission or within 4 weeks of hospitalization, were included. The incidence of HA-CDI and antibiotic utilization from 2003 to 2020 were analyzed with available C. difficile isolates. The impact of antibiotic utilization on HA-CDI incidence was estimated by a dynamic regression time-series model. Antibiotic utilization and the proportion of NAP1/027 strains were compared biannually for available isolates from 2010 to 2020. The incidence of HA-CDI decreased between 2003 and 2020 at both hospitals from 26.5 cases per 10,000 patient-days in 2003 to 4.9 cases per 10,000 patient-days in 2020 respectively. Over the study period, there were an increase in the utilization of third-generation cephalosporins and a decrease in usage of fluoroquinolones and clindamycin. A decrease in fluoroquinolone utilization was associated with a significant decrease in HA-CDI incidence as well as decrease in the NAP1/027 strain by approximately 80% in both hospitals. Decreased utilization of fluoroquinolones in two Québec hospitals was associated with a decrease in the incidence of HA-CDI and a genotype shift from NAP1/027 to non-NAP1/027 strains.

The Need for European Surveillance of CDI.

Since the turn of the millennium, the epidemiology of Clostridioides difficile infection (CDI) has continued to challenge. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and standardised surveillance systems. However, a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has led to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country CDI surveillance program and optimised diagnostic strategies are required has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks led to the development of the European surveillance protocol and an over-arching long-term CDI surveillance strategy for 2014-2020, which has been followed by the development of surveillance systems in at least 20 European countries. However, surveillance activities in individual countries have slowed during the COVID-19 pandemic as resources were diverted to the global health crisis. A renewed and strengthened focus on CDI surveillance and prevention is therefore urgently needed post COVID-19.

Importance of underlying mechanisms for interpreting relative risk of Clostridioides difficile infection among antibiotic-exposed patients in healthcare facilities.

Clostridioides difficile infection (CDI) is a significant public health threat, associated with antibiotic-induced disruption of the normally protective gastrointestinal microbiota. CDI is thought to occur in two stages: acquisition of asymptomatic colonization from ingesting C. difficile bacteria followed by progression to symptomatic CDI caused by toxins produced during C. difficile overgrowth. The degree to which disruptive antibiotic exposure increases susceptibility at each stage is uncertain, which might contribute to divergent published projections of the impact of hospital antibiotic stewardship interventions on CDI. Here, we model C. difficile transmission and CDI among hospital inpatients, including exposure to high-CDI-risk antibiotics and their effects on each stage of CDI epidemiology. We derive the mathematical relationship, using a deterministic model, between those parameters and observed equilibrium levels of colonization, CDI, and risk ratio of CDI among certain antibiotic-exposed patients relative to patients with no recent antibiotic exposure. We then quantify the sensitivity of projected antibiotic stewardship intervention impacts to alternate assumptions. We find that two key parameters, the antibiotic effects on susceptibility to colonization and to CDI progression, are not identifiable given the data frequently available. Furthermore, the effects of antibiotic stewardship interventions are sensitive to their assumed values. Thus, discrepancies between different projections of antibiotic stewardship interventions may be largely due to model assumptions. Data supporting improved quantification of mechanistic antibiotic effects on CDI epidemiology are needed to understand stewardship effects better.

CLINICAL OUTCOME AND SEVERITY OF CLOSTRIDIOIDES (CLOSTRIDIUM) DIFFICILE INFECTION AT A TERTIARY REFERRAL HOSPITAL IN BRAZIL.

•The outcomes of CDI were evaluated in 65 patients with CDI in a Brazilian tertiary hospital. •Lack of clinical improvement after treatment and the severity score (ATLAS) increased the risk of death. •The use of multiple antimicrobial agents was associated with longer hospital stays. •Patients with high Charlson comorbidity index (>7) were more likely to recur. Background - Clostridioides difficile infection (CDI) is a potentially severe disease that can present with refractoriness, recurrence, and evolution to death. In Brazil, the epidemiology of CDI seems to differ from that of the United States and most European countries, with only one ribotype (RT) 027-related case and a high prevalence of RT106. Objective - The aim of this study was to evaluate the outcomes of CDI and its possible association with ribotypes at a university hospital in Brazil. Methods - A total of 65 patients with CDI were included and stool samples were submitted to A/B toxin detection and toxigenic culture, and toxigenic isolates (n=44) were also PCR ribotyped. Results - Patients' median age was 59 (20-87) years and there were 16 (24.6%) deaths. The median Charlson comorbidity index (CCI) was 4 (0-15) and 16.9% of the patients had CCI ≥8. The ATLAS score and non-improvement of diarrhea were related to higher mortality. A longer length of hospitalization was related to the enteral nutrition and use of multiple antibiotics. The period between CDI diagnosis and hospital discharge was longer in those who received new antibiotics after diagnosis, multiple antibiotics, and required intensive care treatment. Recurrence was associated with CCI >7. Twenty ribotypes were identified and RT106 was the most frequently detected strain (43.2%). No relationship was observed between the ribotypes and outcomes. CDI was present in patients with more comorbidities. Conclusion - Risk factors for higher mortality, longer hospital stay and recurrence were identified. A diversity of ribotypes was observed and C. difficile strains were not related to the outcomes.

A new score to predict Clostridioides difficile infection in medical patients: a sub-analysis of the FADOI-PRACTICE study.

Medical divisions are at high risk of Clostridioides difficile infection (CDI) due to patients' frailty and complexity. This sub-analysis of the FADOI-PRACTICE study included patients presenting with diarrhea either at admission or during hospitalization. CDI diagnosis was confirmed when both enzyme immunoassay and A and B toxin detection were found positive. The aim of this sub-analysis was the identification of a new score to predict CDI in hospitalized, medical patients. Five hundred and seventy-two patients with diarrhea were considered. More than half of patientswas female, 40% on antibiotics in the previous 4weeks and 60% on proton pump inhibitors(PPIs). CDI diagnosis occurred in 103 patients (18%). Patients diagnosed with CDI were older, more frequently offemalesex, recently hospitalized and bed-ridden, and treated with antibiotics and PPIs. Through a backward stepwise logistic regression model, age > 65years, female sex, recent hospitalization, recentantibiotic therapy, active cancer, prolonged hospital stay (> 12days), hypoalbuminemia (albumin < 3g/dL), and leukocytosis (white blood cells > 9 × 10^9/L) were found to independently predict CDI occurrence. These variables contributed to building a clinical prognostic score with a good sensitivity and a modest specificity for a value > 3 (79% and 58%, respectively; AUC 0.75, 95% CI 0.71-0.79, p < 0.001), that identified low-risk (score ≤ 3; 42.5%) and high-risk (score > 3; 57.5%) patients. Although some classical risk factors were confirmed to increase CDI occurrence, the changing landscape of CDI epidemiology suggests a reappraisal of common risk factors and the development of novel risk scores based on local epidemiology.

Surveillance and epidemiology of Clostridioides difficile infection using the national health surveillance network criteria: A 7-year study from Mumbai, India

IntroductionClostridioides difficile (CD) is a significant cause of morbidity and mortality. While considerable data is available in the developed world regarding Clostridioides difficile infection (CDI), Indian data is sparse especially using the standardized surveillance systems. Aim and objectives of the studyTo identify the incidence, risk factors, and mortality rate associated with CDI in a tertiary care hospital based on the Laboratory-Identified (LabID) event criteria of the Centers for Disease Control and Prevention (CDC) National Health Surveillance Network (NHSN). Materials and methodsDuring a 7- year prospective observational study, CDI was diagnosed using CD polymerase chain reaction (PCR). CDI Laboratory-Identified (LabID) events were classified using the CDC NHSN surveillance definition, and CDI incidence was calculated per 10,000 Patient Days (PDs). Clinical details were collected as part of healthcare-associated infection (HCAI) surveillance. Healthcare Facility-Onset (HO) and Community-Onset Healthcare Facility-Associated (CO-HCFA) incident CDI events were analyzed further. ResultsAmong 898 tested stool samples, 77 CDI LabID events were observed, with 68 being Incident events. Of 68 events, 76.5% (52/68), 19.1% (13/68), and 4.4% (3/68) were HO, Community-Onset (CO), and CO-HCFA CDI events respectively. The overall incidence of CDI events was 1.66 per 10,000 PDs. Risk factors observed were antibiotics exposure (100%), comorbidities (87.3%), antacids exposure (87.3%), age over 60 years (80%), and hospitalization within the past 6 months (67.3%). The crude mortality rate was 25.5% (14/55). ConclusionThese findings highlight the predominance of HO-CDI and the need for further investigation into CO-CDI in the Indian context to identify at-risk populations. Utilizing standardized surveillance methods such as NHSN definitions can facilitate accurate disease burden estimation, trend monitoring, and meaningful comparisons with global data.

Effect of the COVID-19 Pandemic on Rates and Epidemiology of Clostridioides difficile Infection in One VA Hospital.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on the rates and molecular epidemiology of Clostridioides difficile infection (CDI) within one VA hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI. Hospital data on patients with CDI and recurrent CDI (rCDI) were reviewed both prior to the COVID-19 pandemic (2015 to 2019) and during the pandemic (2020-2021). Restriction endonuclease analysis (REA) strain typing was performed on CD isolates recovered from stool samples collected from October 2019 to March 2022. CDI case numbers declined by 43.2% in 2020 to 2021 compared to the annual mean over the previous 5 years. The stool test positivity rate was also lower during the COVID-19 pandemic (14.3% vs. 17.2%; p = 0.013). Inpatient hospitalization rates declined, and rates of CDI among inpatients were reduced by 34.2% from 2020 to 2021. The mean monthly cases of rCDI also declined significantly after 2020 [3.38 (95% CI: 2.89-3.87) vs. 1.92 (95% CI: 1.27-2.56); p = <0.01]. Prior to the pandemic, REA group Y was the most prevalent CD strain among the major REA groups (27.3%). During the first wave of the pandemic, from 8 March 2020, to 30 June 2020, there was an increase in the relative incidence of REA group BI (26.7% vs. 9.1%); After adjusting for CDI risk factors, a multivariable logistic regression model revealed that the odds of developing an REA group BI CDI increased during the first pandemic wave (OR 6.41, 95% CI: 1.03-39.91) compared to the pre-pandemic period. In conclusion, the incidence of CDI and rCDI decreased significantly during the COVID-19 pandemic. In contrast, REA BI (Ribotype 027), a virulent, previously epidemic CD strain frequently associated with hospital transmission and outbreaks, reappeared as a prevalent strain during the first wave of the pandemic, but subsequently disappeared, and overall CDI rates declined.

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

Background: The epidemiology of Clostridioides difficile infection (CDI) is complex, and the COVID-19 pandemic has had extreme impacts on known risk factors such as comorbidity burden and antibiotic prescribing. However, whether these changes have affected the incidence of hospital-associated CDI (HA-CDI) remains unknown. We compared incidence and trends of HA-CDI before and after the pandemic onset, and we assessed the impact of changes in key CDI-related risk factors. Methods: We conducted an interrupted time-series study (March 2018–March 2021) of adult inpatients hospitalized 4 or more days with no known CDI on admission at a 576-bed academic medical center. Our primary outcome was monthly HA-CDI per 10,000 patient days. We performed segmented linear regression to compare the preinterruption trend in HA-CDI rate to the postinterruption slope and level change. We established a series of 30-day intervals before and after the interruption timepoint of March 23, 2020, which corresponds with the Oregon stay-at-home executive order. The data included 24 preinterruption time points and 12 postinterruption time points. We also assessed changes in slope and trend for known HA-CDI risk factors. Results: We included 34,592 inpatient encounters in our prepandemic period and 10,932 encounters in our postinterruption period. The mean prepandemic HA-CDI rate was 4.07 cases per 10,000 patient days. After the pandemic onset, the rate was 3.6 per 10,000 patient days. However, the observed differences in rate (both in terms of slope and level) were not statistically significant (P = .90 for level; P = .60 for slope change). We observed a significant decrease in admissions per 30 days (1,441 vs 911; level-change P &lt; .0001) and a slight increase in the mean number of Elixhauser comorbidities (1.96 vs 2.07; level-change P = .05). We also observed significant increases in both frequency and intensity of antibiotic use, with an increase average days of therapy per encounter (5.8 vs 7.2; level-change P = .01; slope-change P &lt; .0001) and in antibiotic spectrum index (ASI) points per antibiotic day (4.4 vs 4.9; P &lt; .0001). We observed a consistent downward trend for case days of CDI colonization pressure per hospital day (preinterruption slope P &lt; .0001), which remained consistent after the pandemic onset (P = 0.5 for postinterruption slope change) (Fig. 1). Conclusions: Despite significant increases in high-intensity antibiotic use and comorbidity burden, we did not observe significant differences in HA-CDI after the pandemic onset. This may be due to the significant decrease in colonization pressure in the postpandemic period. Further research is required to fully understand the impact of the pandemic-related changes onDisclosures: None

Trends in the epidemiology of Clostridioides difficile infection in Germany.

Despite reports of a declining incidence over the last decade, Clostridioides difficile infection (CDI) is still considered the most important healthcare-associated causes of diarrhea worldwide. In Germany, several measures have been taken to observe, report, and influence this development. This report aims to analyze the development of hospital coding for CDI in Germany over the last decade and to use it to estimate the public health burden caused by CDI. Reports from the Institute for Hospital Remuneration Systems, German Federal Statistical Office (DESTATIS), the Robert-Koch-Institute (RKI), Saxonian authorities and hospital quality reports during 2010-2021 were examined for CDI coding and assessed in a structured expert consultation. Analysis was performed using 2019 versions of Microsoft Excel® and Microsoft Access®. Peaks of 32,203 cases with a primary diagnosis (PD) of CDI and 78,648 cases with a secondary diagnosis (SD) of CDI were observed in 2015. The number of cases had decreased to 15,412 PD cases (-52.1%) and 40,188 SD cases (-48.9%) by 2021. These results were paralleled by a similar decline in notifiable severe cases. However, average duration of hospitalization of the cases remained constant during this period. Hospital coding of CDI and notification to authorities has approximately halved from 2015 to 2021. Potential influential factors include hospital hygiene campaigns, implementation of antibiotic stewardship programs, social distancing due to the COVID-19 pandemic, and a decrease in more pathogenic subtypes of bacteria. Further research is necessary to validate the multiple possible drivers for this development.

Clostridioides difficile infections were predominantly driven by fluoroquinolone-resistant Clostridioides difficile ribotypes 176 and 001 in Slovakia in 2018–2019

To investigate the epidemiology of Clostridioides difficile infection (CDI) in Slovakian hospitals after the emergence of ribotype 176 (027-like) in 2016. Between 2018 and 2019, European Centre for Disease Control and Prevention CDI surveillance protocol v2.3 was applied to 14 hospitals, with additional data collected on recent antimicrobial use and the characterization of C. difficile isolates. The mean hospital incidence of CDI was 4.1 cases per 10,000 patient bed-days. One hundred and five (27.6%) in-hospital deaths were reported among the 381 cases. Antimicrobial treatment within the previous 4 weeks was recorded in 90.5% (333/368) of cases. Ribotype (RT)176 was detected in 50% (n=185/370, 14 hospitals) and RT001 was detected in 34.6% (n=128/370,13/14 hospitals) of cases with RT data. Overall, 86% (n=318/370) of isolates were resistant to moxifloxacin by Thr82Ile in GyrA (99.7%). Multi-locus variable tandem repeat analysis showed clonal relatedness of predominant RTs within and between hospitals. Seven of 14 sequenced RT176 isolates and five of 13 RT001 isolates showed between zero and three allelic differences by whole-genome multi-locus sequence typing. The majority of sequenced isolates (24/27) carried the erm(B) gene and 16/27 also carried the aac(6')-aph(2'') gene with the corresponding antimicrobial susceptibility phenotypes. Nine RT176 strains carried the cfr(E)gene and one RT001 strain carried the cfr(C) gene, but without linezolid resistance. The newly-predominant RT176 and endemic RT001 are driving the epidemiology of CDI in Slovakia. In addition to fluoroquinolones, the use of macrolide-lincosamide-streptogramin B antibiotics can represent another driving force for the spread of these epidemic lineages. In C. difficile, linezolid resistance should be confirmed phenotypically in strains with detected cfr gene(s).

Epidemiology and Risk Factors of Clostridioidesdifficile Infections in Germany: A Health Claims Data Analysis.

Clostridioidesdifficile infection (CDI) is increasingly recognized as a public health threat at the community level in addition to being one of the most common causes of healthcare-associated infections. In Germany, the epidemiology of CDI is primarily informed by national hospital-based CDI surveillance. We used health claims data from Germany to obtain valuable insights on population-level disease burden and risk factors for CDI. This was a retrospective cohort study using a representative sample from the InGef research database. Overall and age- and sex-stratified CDI incidence rates were estimated for German adults from 2013 to 2017 using different case definitions (i.e., main, broad, strict), and further stratified by setting (inpatient versus outpatient). Risk factors for CDI were assessed for the 2013-2016 period. The CDI incidence rate was high but declined by 15.3% from 2013 [141 (95% confidence interval, CI 137-145) cases/100,000 person-years] to 2017 [120 (95% CI 116-123)]. Annual CDI incidence rates were higher in female patients and the elderly. The most important risk factors for CDI were chronic inflammatory bowel disease [odds ratio (OR) 4.7, 95% CI 4.0-5.5], chemotherapy (OR 4.7, 95% CI 4.1-5.2), chronic kidney disease (OR 2.9, 95% CI 2.6-3.3), and ciprofloxacin receipt (OR 2.6, 95% CI 2.4-2.8). Despite prevention strategies leading to declining incidence, CDI remains an important public health threat in Germany, with a high burden in the hospital setting and an outpatient epidemiology that is poorly understood. These findings, which are relevant both regionally and globally, can be used as a basis for further research on the full burden of CDI in Germany.

Host Sorbitol and Bacterial Sorbitol Utilization Promote Clostridioides difficile Infection in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a widespread gastrointestinal inflammatory disorder with globally increasing incidence. Clostridioides difficile infection (CDI) often occurs in patients with intestinal dysbiosis, such as after antibiotic therapy. Patients with IBD have increased incidence of CDI and the clinical outcome of IBD is reportedly worsened by CDI. However, the underlying reasons remain poorly understood. We performed a retrospective single-center and a prospective multicenter analysis of CDI in patients with IBD, including genetic typing of C difficile isolates. Furthermore, we performed a CDI mouse model to analyze the role of the sorbitol metabolization locus that we found distinguished the main IBD- and non-IBD-associated sequence types (STs). Moreover, we analyzed sorbitol concentration in the feces of patients with IBD and healthy individuals. We detected a significant association of specific lineages with IBD, particularly increased abundance of ST54. We found that in contrast tothe otherwise clinically predominant ST81, ST54 harborsasorbitol metabolization locus and was able to metabolize sorbitol invitro and invivo. Notably, in the mouse model, ST54 pathogenesis was dependent on intestinal inflammation-induced conditions and the presence of sorbitol. Furthermore, we detected significantly increased sorbitol concentrations in the feces of patients with activeIBD vs patients in remission or healthy controls. Sorbitol and sorbitol utilization in the infecting C difficile strain play major roles for the pathogenesis and epidemiology of CDI in patients with IBD. CDI in patients with IBD may thus be avoided or improved by elimination of dietary sorbitol or suppression of host-derived sorbitol production.

Clostridioides difficile infection epidemiology and clinical characteristics in COVID-19 pandemic.

Information on Clostridioides difficile infection (CDI) in patients with COVID-19 is scarce and points to an overall decrease of episodes during the pandemic. This situation results paradoxical, as COVID-19 patients had long periods of hospital stay and high use of antibiotics. We conducted a retrospective study from January 1st 2019 to December 31st 2020 comparing the incidence of hospital-acquired episodes of CDI (HA-CDI) among patients with and without COVID-19 admitted to our institution. During the study period, there were 47,048 patient admissions in 2019, 35,662 admissions of patients without COVID-19 in 2020 and 6,763 of COVID-19 patients. There were 68 episodes of HA-CDI in COVID-19 patients (14.75/10,000 days), 159 in 2020-non-COVID-19 patients (5.54/10,000 days) and 238 in 2019 (6.80/10,000 days). Comparison of HA-CDI in COVID-19 and non-COVID-19 patients indicates it occurs more frequently, in terms of CDI disease severity, COVID-19 does not seem to have a negative impact.