Incidence Of Clostridioides Difficile Infection Research Articles

Impact of the COVID-19 pandemic on Clostridioides difficile infection in a tertiary healthcare institution in Belgium

ABSTRACT Objectives Clostridioides difficile infection (CDI) causes the greatest number of healthcare-associated infectious diarrhoea. CDIs are transmitted by direct and indirect patient-to-patient contact and risk increases with the use of antibiotics. Since early 2020, the COVID-19 pandemic has affected healthcare systems in many ways including substantial changes in hygiene behaviour. The aim of this study was to assess whether CDI incidence differed during the COVID-19 pandemic compared to a year before. Methods All tests for suspected CDI cases were recorded for a hospital in Brussels, Belgium. The percentage of CDI-positive results and incidences (total and healthcare-associated (HA)-CDI)) for years 2019, 2020, 2021, and 2022 were calculated. Antibiotic consumption was analysed for years 2019 and 2020. Results Since the COVID-19 pandemic struck, a significant reduction of up to 39% was observed in the number of Clostridioides difficile stool tests in our hospital. A significant decrease in the percentage of positive tests and a 50% decrease in the incidence of CDI (total and HA-CDI) was found for 2020 compared with 2019 and confirmed for years 2021 and 2022. The decrease in CDI incidence was mostly marked in haematology, nephrology, and gastroenterology units. No significant change in the use of antibiotics was found. Conclusion The global decrease in CDI incidence observed in our hospital was not associated with a change in the use of antibiotics. The control measures implemented to prevent COVID-19 transmission may explain a reduction in CDI incidence. An underdiagnosis of CDI cannot be excluded.

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.

Prevention and treatment of C. difficile in cancer patients.

We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients. Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates. Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.

Oral Omilancor Treatment Ameliorates Clostridioides difficile Infection During IBD Through Novel Immunoregulatory Mechanisms Mediated by LANCL2 Activation.

Clostridioides difficile infection (CDI) is an opportunistic infection of the gastrointestinal tract, commonly associated with antibiotic administration, that afflicts almost 500 000 people yearly only in the United States. CDI incidence and recurrence is increased in inflammatory bowel disease (IBD) patients. Omilancor is an oral, once daily, first-in-class, gut-restricted, immunoregulatory therapeutic in clinical development for the treatment of IBD. Acute and recurrent murine models of CDI and the dextran sulfate sodium-induced concomitant model of IBD and CDI were utilized to determine the therapeutic efficacy of oral omilancor. To evaluate the protective effects against C. difficile toxins, in vitro studies with T84 cells were also conducted. 16S sequencing was employed to characterize microbiome composition. Activation of the LANCL2 pathway by oral omilancor and its downstream host immunoregulatory changes decreased disease severity and inflammation in the acute and recurrence models of CDI and the concomitant model of IBD/CDI. Immunologically, omilancor treatment increased mucosal regulatory T cell and decreased pathogenic T helper 17 cell responses. These immunological changes resulted in increased abundance and diversity of tolerogenic gut commensal bacterial strains in omilancor-treated mice. Oral omilancor also resulted in accelerated C. difficile clearance in an antimicrobial-free manner. Furthermore, omilancor provided protection from toxin damage, while preventing the metabolic burst observed in intoxicated epithelial cells. These data support the development of omilancor as a novel host-targeted, antimicrobial-free immunoregulatory therapeutic for the treatment of IBD patients with C. difficile-associated disease and pathology with the potential to address the unmet clinical needs of ulcerative colitis and Crohn's disease patients with concomitant CDI.

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.

Assessing the Impact of 2-Step Clostridioides difficile Testing at the Healthcare Facility Level.

Two-step testing for Clostridioides difficile infection (CDI) aims to improve diagnostic specificity but may also influence reported epidemiology and patterns of treatment. Some providers fear that 2-step testing may result in adverse outcomes if C. difficile is underdiagnosed. Our primary objective was to assess the impact of 2-step testing on reported incidence of hospital-onset CDI (HO-CDI). As secondary objectives, we assessed the impact of 2-step testing on C. difficile-specific antibiotic use and colectomy rates as proxies for harm from underdiagnosis or delayed treatment. This longitudinal cohort study included 2 657 324 patient-days across 8 regional hospitals from July 2017 through March 2022. Impact of 2-step testing was assessed by time series analysis with generalized estimating equation regression models. Two-step testing was associated with a level decrease in HO-CDI incidence (incidence rate ratio, 0.53 [95% confidence interval {CI}, .48-.60]; P < .001), a similar level decrease in utilization rates for oral vancomycin and fidaxomicin (utilization rate ratio, 0.63 [95% CI, .58-.70]; P < .001), and no significant level (rate ratio, 1.16 [95% CI, .93-1.43]; P = .18) or trend (rate ratio, 0.85 [95% CI, .52-1.39]; P = .51) change in emergent colectomy rates. Two-step testing is associated with decreased reported incidence of HO-CDI, likely by improving diagnostic specificity. The parallel decrease in C. difficile-specific antibiotic use offers indirect reassurance against underdiagnosis of C. difficile infections still requiring treatment by clinician assessment. Similarly, the absence of any significant change in colectomy rates offers indirect reassurance against any rise in fulminant C. difficile requiring surgical management.

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

Effects of a hard stop for C. difficile testing: Provider uptake and patient outcomes

Background:Clostridioides difficile infection (CDI) is a serious healthcare-associated infection responsible for &gt;12,000 US deaths annually. Overtesting can lead to antibiotic overuse and potential patient harm when patients are colonized with C. difficile, but not infected, yet treated. National guidelines recommend when testing is appropriate; occasionally, guideline-noncompliant testing (GNCT) may be warranted. A multidisciplinary group at UNC Medical Center (UNCMC) including the antimicrobial stewardship program (ASP) used a best-practice alert in 2020 to improve diagnostic stewardship, to no effect. Evidence supports use of hard stops for this purpose, though less is known about provider acceptance. Methods: Beginning in May 2022, UNCMC implemented a hard stop in its electronic medical record system (EMR) for C. difficile GNCT orders, with exceptions to be approved by an ASP attending physician. Requests were retrospectively reviewed May–November 2022 to monitor for adverse patient outcomes and provider hard-stop compliance. The team exported data from the EMR (Epic Systems) and generated descriptive statistics in Microsoft Excel. Results: There were 85 GNCT orders during the study period. Most tests (62%) were reviewed by the ASP, and 38% sought non-ASP or no approval. Of the tests reviewed by the ASP, 33 (62%) were approved and 20 (38%) were not. Among tests not approved by the ASP, no patients subsequently received CDI-directed antibiotics, and 1 patient (5%) warranted same-admission CDI testing (negative). Of tests that circumvented ASP review, 18 (56%) ordering providers received a follow-up email from an associate chief medical officer to determine the rationale. No single response type dominated: 3 (17%) were unaware of the ASP review requirement, 2 (11%) indicated their patient’s uncharted refusal of laxatives, 2 (11%) indicated another patient-specific reason. Provider avoidance of the ASP approval mechanism decreased 38%, from 53% of noncompliant tests in month 1 to 33% of tests in month 6. Total tests orders dropped 15.5% from 1,129 during the same period in 2021 to 954 during the study period (95% CI, 13.4%–17.7%). Compliance with the guideline component requiring at least a 48-hour laxative-free interval prior to CDI testing increased from 85% (95% CI, 83%–87%) to 95% (95% CI, 93%–96%). CDI incidence rates decreased from 0.52 per 1,000 patient days (95% CI, 0.41–0.65) to 0.41 (95% CI, 0.32–0.53), though the change was neither significant at P = .05 nor attributable to any 1 intervention. Conclusions: Over time and with feedback to providers circumventing the exception process, providers accepted and used the hard stop, improving diagnostic stewardship and avoiding unneeded treatment.Disclosures: None

Clostridioides difficile - New Insights and Therapy Recommendations

After an increase in Clostridioides difficile infections (CDI) until 2013 due to epidemic ribotypes such as 027 and 078, CDI incidence in Germany is now declining, as confirmed by recent epidemiological data. Despite this success through antimicrobial stewardship and hospital hygiene, the burden of disease remains high, especially in older patients (>65 years) with comorbidities. The main risk factor for CDI is the use of broad-spectrum antibiotics, which disrupt the gut microbiota, allowing C. difficile colonization. Coinfection with other intestinal pathogens such as enterococci can further increase the virulence of C. difficile. The updated 2021 ESCMID guidelines recommend fidaxomicin instead of vancomycin as the antibiotic of choice for the treatment of CDI because of its lower recurrence rate. Vancomycin remains a good alternative; however, metronidazole should only be used if neither antibiotic is available. In the future, ridinilazole may be available as another therapeutic option that has a narrow spectrum of activity and low intestinal absorption. For the treatment of recurrent CDI, the new guidelines also include the use of the monoclonal antibody bezlotoxumab. In addition, a new oral microbiome therapy, SER-109 (capsules containing purified Firmicutes spores), which showed promising results in a phase 3 study, may provide an easy-to-administer alternative to fecal microbiota transplantation. Hopes for a well-performing toxoid vaccine for primary and secondary prevention of CDI have unfortunately not been fulfilled in the CLOVER trial.

&lt;i&gt;Clostridioides difficile&lt;/i&gt; infection: diagnosis, treatment, and prevention Clinical guidelines of the Russian Scientific Medical Society of Internal Medicine, the Gastroenterological Scientific Society of Russia, and the North- West Society of Gastroenterologists and Hepatologists

Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea, and an important cause of nosocomial infection. Since the publication of the National Guidelines (2016, 2017), new data have been accumulated on the genetic structure and pathogenic properties of the most common causative agent of severe forms of antibiotic- associated diarrhea, which has led to the reclassifi cation of the pathogen, formerly known as Clostridium diffi cile, to Clostridioides difficile. Laboratory algorithms have been developed to diagnose CDI and determine the toxigenicity of strains reliably. New data on the effectiveness of antibacterials have been published, monoclonal antibodies to toxin B (bezlotoxumab) have been introduced into clinical practice to prevent CDI recurrence, and fecal microbiota transplantation has been proposed. Over the past 5 years, many international guidelines on the management of adult patients with CDI have also been updated (USA, EU). In the last decade, including due to the COVID-19 pandemic, there has been an increase in CDI incidence. Considering therelevance of CDI, new data on the pathogen, and domestic features, the Russian Scientific Medical Society of Internal Medicine, the Gastroenterological Scientific Society of Russia, and the North-West Society of Gastroenterologists and Hepatologists developed these clinical guidelines.

Cefepime Versus Piperacillin-Tazobactam for the Treatment of Intra-Abdominal Infections Secondary to Potential AmpC Beta-Lactamase-Producing Organisms.

Background: Recent studies have established cefepime as an effective treatment option for AmpC beta-lactamase (AmpC) Enterobacterales; however, the efficacy of beta-lactam/beta-lactamase inhibitors is unclear. Objective: The objective of this study was to determine if piperacillintazobactamis an appropriate alternative to cefepime for the treatment of intra-abdominal infections (IAIs) secondary to AmpC-producing organisms. Methods: This multicenter, retrospective cohort study was conducted in hospitalized adults with an IAI caused by an AmpC-producing organism and received either cefepime or piperacillin-tazobactam for definitive treatment after a source control procedure. The primary outcome was a composite of surgical site infections, recurrent IAIs, or in-hospital mortality. Secondary outcomes included the individual components of the composite outcome, hospital length of stay (LOS), microbiologic failure, study antibiotic duration, time to clinical resolution, and incidence of Clostridioides difficile infection (CDI). Results: This study included 119 patients. There was no difference in the primary outcome between the cefepime and piperacillin-tazobactam groups (35% vs 27%, P = 0.14). Microbiological failure was the only secondary outcome with an observed difference between groups (17% vs 0%, P = 0.01): hospital LOS (15 vs 13 days, P = 0.09), days of therapy (7 vs 7 days, P = 0.87), time to clinical resolution (7 vs 4 days, P = 0.30), and CDI (1% vs 2%, P = 0.58) were all similar.

COVID-19 and Clostridioides difficile Coinfection Outcomes among Hospitalized Patients in the United States: An Insight from National Inpatient Database.

The incidence of Clostridioides difficile infection (CDI) has been increasing compared to pre-COVID-19 pandemic levels. The COVID-19 infection and CDI relationship can be affected by gut dysbiosis and poor antibiotic stewardship. As the COVID-19 pandemic transitions into an endemic stage, it has become increasingly important to further characterize how concurrent infection with both conditions can impact patient outcomes. We performed a retrospective cohort study utilizing the 2020 NIS Healthcare Cost Utilization Project (HCUP) database with a total of 1,659,040 patients, with 10,710 (0.6%) of those patients with concurrent CDI. We found that patients with concurrent COVID-19 and CDI had worse outcomes compared to patients without CDI including higher in-hospital mortality (23% vs. 13.4%, aOR: 1.3, 95% CI: 1.12-1.5, p = 0.01), rates of in-hospital complications such as ileus (2.7% vs. 0.8%, p < 0.001), septic shock (21.0% vs. 7.2%, aOR: 2.3, 95% CI: 2.1-2.6, p < 0.001), length of stay (15.1 days vs. 8 days, p < 0.001) and overall cost of hospitalization (USD 196,012 vs. USD 91,162, p < 0.001). Patients with concurrent COVID-19 and CDI had increased morbidity and mortality, and added significant preventable burden on the healthcare system. Optimizing hand hygiene and antibiotic stewardship during in-hospital admissions can help to reduce worse outcomes in this population, and more efforts should be directly made to reduce CDI in hospitalized patients with COVID-19 infection.

Implication of COVID-19 pandemic on the incidence of Clostridioides difficile infection in a Greek tertiary hospital.

Introduction. C. difficile infection (CDI) represents an important global threat. In the COVID-19 era, the multifactorial nature of CDI has emerged.Hypothesis - Aim. The aim was to assess the impact of COVID-19 pandemic on the incidence of CDI in a Greek hospital.Methodology. A retrospective study was performed throughout a 51 month period (January 2018 to March 2022), divided into two periods: pre-pandemic (January 2018 to February 2020) and COVID-19 pandemic (March 2020 to March 2022). The effects of the pandemic compared to the pre-pandemic period on the incidence of CDI [expressed as infections per 10 000 bed days (IBD)] were studied using interrupted time-series analysis.Results. Throughout the study, there was an increase in the monthly CDI incidence from 0.00 to 11.77 IBD (P<0.001). Interrupted time-series disclosed an increase in CDI incidence during the pre-pandemic period from 0.00 to 3.36 IBD (P<0.001). During the COVID-19 pandemic period the linear trend for monthly CDI rose from 2.65 to 13.93 IBD (P<0.001). The increase rate was higher during the COVID-19 pandemic period (r2 = +0.47) compared to the pre-pandemic period (r1 = +0.16).Conclusion. A significant increase of CDI incidence was observed, with the rate of the rise being more intense during the COVID-19 pandemic.

Low prevalence of Clostridioides difficile infection in acute severe ulcerative colitis: A retrospective cohort study from northern India.

The incidence of Clostridioides difficile infection (CDI) is high in ulcerative colitis and is associated with disease flares and adverse outcomes. However, the data on the dynamics of CDI in patients with acute severe ulcerative colitis (ASUC) is rather scarce. We evaluated the prevalence of CDI in patients with ASUC. This retrospective analysis of a prospectively maintained cohort admitted to the All India Institute of Medical Sciences, India, from May 2016 to December 2021, included patients with ASUC (as per Truelove and Witts criteria) who were tested for CDI. CDI testing was performed using enzyme-linked immunoassay for toxins A and B. Risk factors for developing CDI were analyzed along with short-term outcomes of ASUC. Steroid failure was defined as the need for medical rescue therapy or colectomy. Total 153 patients with ASUC were included (mean age 34.92 ± 12.24years; males 56.2%; disease duration 36 (IQR: 16-55.5) months, pancolitis 67.3%). Ninety-eight (63.4%), 72 (47%) and 10 (6.5%) patients, respectively, had received steroids, azathioprine and biologics in the past. Forty patients (26.14%) had a prior history of ASUC. Among risk factors for CDI, 14% of the patients had prior admission within 30days, 22.2% had a recent history of antibiotics and 3.9% had long-term non-steroidal anti-inflammatory drug intake. Only one sample was positive for Clostridioides difficile toxin assay. Tissue Cytomegalovirus DNA-PCR positivity was noted in 57 patients (37.3%). Fifty-seven patients (37.3%) had steroid failure, 35 required medical rescue therapy and 30 (19.6%) required colectomy (eight after medical rescue therapy failure). Despite antecedent risk factors for CDI, the overall prevalence of CDI in ASUC was low and theoutcomes were determined by underlying disease severity.

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI.

An obituary on DAV-132—authors’ viewpoint on the current limits of pivotal trials in clinical microbiome research

There is an urgent need for novel approaches to reduce the spread and clinical impact of infections with MDR bacteria. Da Volterra (Paris, France) is a biopharmaceutical company specializing in the development of microbiota-protective therapies. In 2010, they introduced DAV-132, an active charcoal preparation designed to protect the gut microbiota from antibiotic selection pressure, without affecting antibiotic pharmacokinetics, at the Superbugs and Superdrugs Conference in London, UK.1 In 2016, Da Volterra joined the EU Innovative Medicines Initiative (IMI) to further develop this promising product in close cooperation with academic partners. Phase I and II trials were completed successfully, confirming the protective effect of DAV-132 on the human gut microbiota.2,3 Consequently, a Phase III trial—MICROCARE—was planned and initiated. On 2 December 2022, however, the company Da Volterra was declared bankrupt. Given the significant clinical potential of DAV-132, this turn of events can be considered tragic. Could it have been avoided? The authors of this letter were closely involved in the design and conduct of the Phase III trial necessary for registration of DAV-132, which was classified as a medical device by the competent authorities. Many hurdles had to be overcome to design and implement a trial that would be feasible to execute. To meet EMA and FDA registration criteria, it was necessary to show that DAV-132 could confer a health benefit. Protecting the microbiota is a very useful property, but is not considered a health benefit per se and is not recognized as a surrogate endpoint. Therefore, an alternative clinical endpoint had to be identified. The evidence on potential health benefits associated with a balanced human microbiota seems to be growing exponentially.4 At the same time, very little of that evidence is quantifiable and directly relatable to endpoints recognized by regulators. For the Phase III trial, we needed patients with considerable antibiotic exposure. These would have to experience a measurable clinical outcome associated with their antibiotic exposure. In addition, the frequency of this outcome to occur would need to be high enough to result in a feasible sample size. The only indication that seemed to fit these criteria was the prevention of Clostridioides difficile infections (CDI). Even though CDI is considered the most frequent healthcare-associated infectious cause of diarrhoea, its overall incidence is declining. Predicting which individual patient might develop CDI remains a major challenge, despite the identification of age and intense antibiotic exposure as key risk factors for CDI.5,6 In patients undergoing induction chemotherapy for AML or high-risk myelodysplastic syndrome the frequent co-occurrence of the latter risk factors results in a relatively high cumulative incidence of CDI, ranging from 9.4% to 23.8% within the first 120 days after initiation of induction chemotherapy.7–10 Even in this selected population, a sample size of 900 was deemed necessary to show the prophylactic efficacy of DAV-132, while assuming a clinical efficacy of DAV-132 of 50% reduction in CDI cases. At the same time, selecting such a seriously ill patient population involves risks. Chemotherapy-associated side effects can significantly impair patient compliance with trial protocols, and an increased number of serious adverse events is to be expected in this population. However, given that the sample sizes calculated for all other populations were not within a realistic range, we were left with the choice of no trial versus a trial with a considerable risk of failure.

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).

Impact of Clostridioides difficile length of treatment on rates of recurrence in patients on concurrent antibiotics

Clostridioides difficile infection (CDI) is principally health care-associated, with a substantial impact on morbidity and mortality. The guidelines recommend CDI therapy for 10 days; however, it is often extended in practice when concurrent antibiotics are used. The impact of the extended duration of therapy remains unclear. To compare the rates of CDI recurrence in patients receiving standard duration of therapy (SDT) with those receiving extended duration of therapy (EDT) for the treatment of hospital-acquired CDI (HA-CDI) while receiving concurrent antibiotics. A retrospective chart review was conducted between October 2017 and 2019. Adult HA-CDI patients who received a minimum 10 days of CDI therapy and were on concurrent antibiotics were stratified into SDT and EDT groups. Rates of CDI recurrence (at 90 and 180 days) and incidence of new-onset vancomycin-resistant enterococcus (VRE) were compared. Two hundred twenty-three patients met the inclusion criteria (SD-106, EDT-117). CDI recurrence rates at 90 and 180 days were not statistically significant between SDT and EDT groups (22% vs 26%, P=.40% and 26% vs 31%, P=.47). Although the incidence of VRE within the extended group was higher, it was not statistically significant (6% vs 9%, P=.29). No significant difference in rates of recurrence or new-onset VRE was observed between SDT and EDT in HA-CDI patients.

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.