Clostridium Difficile Infection Cases Research Articles

S730 Vedolizumab Is Associated With Lower Risk of Clostridioides difficile Infection Compared to Anti-TNF Alpha Agents Among Biologic-Naïve Patients With Ulcerative Colitis

Introduction: Clostridioides difficile infection (CDI) is a complication of ulcerative colitis (UC) that is associated with poor outcomes. It is unknown if vedolizumab (VDZ), which inhibits lymphocyte trafficking to intestinal mucosa, confers a greater risk of CDI compared to anti-TNF agents. We sought to compare CDI rates between VDZ and anti-TNFs among biologic-naïve patients with UC. Methods: Retrospective cohort study of adult, biologic-naïve UC patients initiating VDZ or anti-TNFs (infliximab or adalimumab) 6/1/14-11/30/20 at a large academic center. Electronic health records were reviewed for clinical data. The primary outcome was time to CDI after biologic initiation, defined by positive PCR or toxin immunoassay with need for CDI treatment. Secondary outcomes were CDI hospitalization and colectomy within 30 days of CDI diagnosis. Inverse probability of treatment weighting (IPTW) was used to adjust for treatment selection bias based on the following variables at/preceding biologic initiation: age, disease duration, systemic corticosteroid use, hospitalization within prior 12 months, Mayo endoscopic subscore, disease extent, and albumin. Kaplan-Meier analysis (KMA) and IPT-weighted Cox regression were used to compare CDI rates by biologic group. Two covariates were included in the weighted Cox model: biologic group and history of pre-biologic CDI. Patients were censored at loss of follow-up, biologic discontinuation, colectomy, or death. Results: 503 UC patients initiated anti-TNFs (n=363) or VDZ (n=140). There was history of pre-biologic CDI in 12.4% of anti-TNF vs 5.7% of VDZ patients (p=0.03) at a median of 167 days (IQR 45, 625 days) prior to biologic initiation (Table 1). Over median follow-up of 425 days after biologic initiation (IQR 154, 959 days), there were 23 cases of CDI (22/363 anti-TNF, 1/140 VDZ, p< 0.01) and 15 CDI hospitalizations (14/363 anti-TNF, 1/140 VDZ, p=0.05). One patient (anti-TNF) required colectomy within 30 days. KMA showed separation in CDI rate curves (p< 0.01, log-rank test) (Figure 1). After IPTW Cox regression, VDZ was associated with a significantly lower hazard of CDI compared to anti-TNFs (HR 0.08, 95% CI 0.01-0.66). Pre-biologic CDI history was associated with greater hazard of CDI (HR 11.38, 95% CI 4.23-30.58). Conclusion: After adjusting for confounders and prior CDI history, VDZ was associated with lower-risk of CDI vs anti-TNFs. This data should be considered when UC patients with history of prior CDI are choosing their first biologic agent.Table 1.: Change in WPAI-CD Scores (Percent Impairment) From Baseline to Week 52 Among Patients Treated With UST or ADA.Figure 1.: Reduction in WPL-associated Costs from Baseline to Week 52 Among Patients Treated With UST or ADA Note: No statistical testing was performed between treatment groups. USD = U.S. dollars.

S183 Infusion of Bezlotoxumab at the End of an Antibiotic Treatment Course for Prevention of Recurrent Clostridioides difficile Infection

Introduction: Clostridioides difficile infection (CDI) is the leading cause of infectious diarrhea in the western world. Despite proper antibiotic treatment, recurrence is common, occurring in 25% of patients after first infection. The risk of recurrence increases with each subsequent episode. Bezlotoxumab is a monoclonal antibody given as adjuvant therapy directed against CD toxin B. The proposed mechanism is that it enters the intestinal lumen through damaged gap junctions and prevents recurrence by neutralizing toxin B produced by residual CD spores which germinate after cessation of antibiotics. In the MODIFY I/II trials, Bezlotoxumab reduced recurrent CDI (rCDI) in comparison to placebo by 10%. Moreover, sustained clinical cure at 12 weeks was achieved with Bezlotoxumab in 64% of subjects as compared to 54% of placebo-arm subjects. While timing of Bezlotoxumab administration was studied during the MODIFY I/II trial, there is a paucity of data regarding the timing of infusion in real world scenarios. Methods: We performed a retrospective study of CDI cases at an academic community hospital in a tri-county area. Inclusion criteria included at least one prior rCDI, defined as CDI within less than three months of resolution of a prior episode, and having received infusion of Bezlotoxumab within 48 hours of final dose of antibiotic for rCDI. For these patients, metrics reviewed include whether rCDI occurred following Bezlotoxumab, patient characteristics including medical co-morbidities, and overall medical risk as denoted by Charlson Comorbidity Index. Results: Six patients fit inclusion criteria. 5/6 patients did not experience rCDI following Bezlotoxumab infusion (Table 1). Patient 5 had underlying Ulcerative Colitis and developed rCDI 11 days after Bezlotoxumab but was then cured after 2 fecal microbiota transplant procedures. 4/5 patients whose CDI resolved experienced a self-limited diarrhea episode within 14 days of infusion that resolved without additional intervention. Conclusion: Infusion of Bezlotoxumab near the end of antibiotic therapy appears to be effective for prevention of rCDI in a real-world setting, and thus provides a simple regimen for treatment. We hypothesize that administration of Bezlotoxumab at the end of a treatment course maximizes its efficacy by ensuring a high antibody titer during the period of high risk for rCDI. Future studies should include higher number of patients and direct comparisons against patients receiving Bezlotoxumab earlier in CDI therapy.Table 1.: Patient Demographics and CDI Recurrence after Bezlotoxumab.

S2941 Fecal Microbiota Transplant in Recurrent Clostridium difficile Enteritis Following Colectomy

Introduction: Fecal microbiota transplant (FMT) is well-known as treatment for recurrent Clostridium difficile infection (CDI). It is curative in 80% of severe or fulminant CDI cases. In this case, we explore the utility of FMT in a patient with recurrent C. diff enteritis (CDE) after colectomy with ileorectal anastomosis. Case Description/Methods: A 46 yr old woman underwent abdominal colectomy with ileostomy 05/2020 with ileorectal anastomosis 07/2020 for severe colonic inertia and h/o ligament release for Median Arcuate Ligament Syndrome in 2/2021. She initially presented with RUQ abdominal pain, nausea, vomiting and diarrhea during the 1st episode of CDI in 10/2020 which was treated with Vancomycin 125mg PO QID for 10 days. Symptoms recurred a month later, C. diff toxin (CDT)+, and this 2nd episode was treated with 3 weeks of Vancomycin 125mg PO QID. Symptoms resolved but recurred 5 months later with hospital admission, again CDT+. CBC and renal function were normal. CT abdomen/pelvis showed nonspecific prominent fluid-filled loops of proximal and mid small bowel consistent with focal ileus or enteritis. Patient was treated for the 3rd time on a prolonged Vancomycin taper (125mg QID x 10 days, 125mg TID x 7 days, 125mg BID x 7 days, 125mg QD x 7 days, 125mg QOD x 14 days) with plans for FMT. She was readmitted 2 months later for pain, nausea, vomiting and diarrhea, CDT-, and underwent planned FMT. FMT was performed via flexible sigmoidoscopy reaching 70cm proximal to the anus with 250cc of donor fecal material mixed with saline (Open Biome). Since FMT, patient has reported resolution of symptoms. Discussion: FMT for recurrent CDI in patients s/p colectomy is not well-documented. A small series of patients s/p colectomy over 20 years showed recurrent CDE does occur after colectomy, and results in severe disease in half of patients, requiring hospitalization in 81%. Risk factors for CDE were colectomy for IBD, colectomy for fulminant CDI, β-lactam use with enteral feeds, and acid suppression after colectomy. Cases of fulminant CDE with multiorgan failure and death have been reported (diagnosed post-mortem). A young man with UC s/p colectomy with IPAA with recurrent CDE was effectively treated with FMT. While rare, recurrent CDE is potentially fatal and warrants consideration of FMT as a treatment modality. Though our patient did not have IBD, was not immunosuppressed and underwent colectomy for reasons unrelated to IBD, the recurrent CDE was effectively treated with FMT.

Management of nosocomial infection of Clostridium difficile : surveillance, prevention and control

In recent years, the incidence of Clostridium difficile infection (CDI) has been in increase worldwide. Effective surveillance is the key to control the incidence and spread of CDI. The content of CDI surveillance mainly includes case definition, standardized diagnosis, CDI case source definition, CDI incidence and suggestions for CDI prevention and control. This review summarizes the pivotal components of effective CDI surveillance, and provides some practical prevention and control suggestions for the standardized surveillance and prevention and control of CDI in hospitals in China.

Diagnosis of Clostridioides difficile infection by analysis of volatile organic compounds in breath, plasma, and stool: A cross-sectional proof-of-concept study.

Clostridioides difficile infection (CDI) is an important infectious cause of antibiotic-associated diarrhea, with significant morbidity and mortality. Current diagnostic algorithms are based on identifying toxin by enzyme immunoassay (EIA) and toxin gene by real-time polymerase chain reaction (PCR) in patients with diarrhea. EIA's sensitivity is poor, and PCR, although highly sensitive and specific, cannot differentiate infection from colonization. An ideal test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection, and assess prognosis and recurrence. The study of volatile organic compounds (VOCs) has the potential to be an ideal diagnostic test. The presence of VOCs accounts for the characteristic odor of stool in CDI but their presence in breath and plasma has not been studied yet. A cross-sectional proof-of-concept study analyzing VOCs using selected ion flow tube mass spectrometry (SIFT-MS) was done on breath, stool, and plasma of patients with clinical features and positive PCR for CDI (cases) and compared with patients with clinical features but a negative PCR (control). Our results showed that VOC patterns in breath, stool, and plasma, had good accuracy [area under the receiver operating characteristic curve (ROC) 93%, 86%, and 91%, respectively] for identifying patients with CDI.

Influence of Probiotics on the Development of Clostridioides difficile Infection in Patients Receiving Fluoroquinolones.

Fluoroquinolones are associated with an increased risk of Clostridioides difficile infection (CDI). Probiotic supplementation has been shown to reduce the risk of antibiotic-associated diarrhea with variable effects on CDI. The objective of this study was to evaluate receipt of probiotics on development of primary CDI among hospitalized patients receiving fluoroquinolones. A retrospective cohort was evaluated that consisted of two groups of 100 patients each, admitted August 2018 through August 2020 that received ≥3 days of definitive monotherapy with levofloxacin or ciprofloxacin within 72 h of admission. Primary outcome was incidence of CDI. Secondary outcomes included rates of C. difficile diagnostic stool testing, additional infectious diagnostic testing, and non-CDI related gastrointestinal side effects. Patients on fluoroquinolones who received probiotics had a non-statistically significantly lower incidence in overall cases of CDI compared to those who did not receive probiotics (0% vs. 3%, p = 0.246). Patients who received probiotics had statistically significantly fewer C. difficile diagnostic stool tests performed (4% vs. 16%, p = 0.005) and fewer additional infectious diagnostic testing performed (4% vs. 10%, p = 0.096), respectively. Further research is warranted to optimize and standardize probiotic prescribing in high-risk patients.

Implementation of control measures against an outbreak due to Clostridioides difficile producing toxin B in a tertiary hospital in Mexico.

SummaryIntroductionTo describe the outbreak of Clostridioides difficile infection (CDI), and the impact of the prevention and control measures that were implemented in the “Hospital Juárez de México” (HJM) for its control.MethodsA cross-sectional, descriptive, observational, and retrospective study was designed. All information on the hospital outbreak and on health care-associated infections (HCAI) was obtained from the files of the Hospital Epidemiological Surveillance Unit (HESU) of the HJM.ResultsA total of 15 cases of CDI were detected from February 20th to May 22nd, 2018, which represented 55.6% and 44.4% for the male and female gender, respectively, with an average age of 56 years and a range of 24 to 86 years old. It was possible to identify six failures and deficiencies that involved health personnel and hospital logistics through analyses based on the situational diagnosis in the services involved and through the construction of cause-effect diagrams. Additionally, through the detection of the outbreak by means of laboratory tests and timeline, the HESU team implemented measures and prospective surveillance to control and prevent the emergence of new cases.ConclusionsThe implementation of basic quality tools, control measures, and the prospective epidemiological surveillance had a positive impact on the control against the outbreak of C. difficile producing toxin B.

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BackgroundFaecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.MethodsWe invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.FindingsIn 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10–64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100–28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.InterpretationFMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.FundingNordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056–00006B).

Did Clostridioides difficile Testing and Infection Rates Change During the COVID-19 Pandemic?

Background: The COVID-19 pandemic has underscored the importance of ongoing infection prevention efforts. Increased adherence to infection prevention recommendations, increased antibiotic use, improved hand hygiene, and correct donning and doffing of personal protective equipment may have influenced healthcare-associated infections (HAIs) in the United States during the pandemic. In this study, we investigated testing for Clostridioides difficile infection (CDI) and incidence during the initial surge of the pandemic. We hypothesized that strict adherence to contact precautions may have resulted in a decreased incidence of CDI in hospitalized patients during the first peak of the COVID-19 pandemic and that CDI testing may have increased even in the absence of directed diagnostic stewardship efforts. Methods: We conducted a single-center, retrospective, observational study at the Veterans’ Affairs (VA) Hospital in Ann Arbor, Michigan, between January 2019 and June 2020. We compared data on CDI tests from January 2019 through February 2020 to data from March 2020 (the admission of the first patient with COVID-19 at our institution) through June 2020. Pre-peak and peak periods were defined by confirmed cases in Washtenaw County. No novel diagnostic or CDI-focused stewardship interventions were introduced by the antimicrobial stewardship program during the study period. An interrupted time series analysis was performed using STATA version 16.1 software (StataCorp LLC, College Station, TX). Results: There were 6,525 admissions and 34,533 bed days between January 1, 2019, and June 30, 2020. Also, 900 enzyme immunoassay (EIA) tests were obtained and 104 positive cases of CDI were detected between January 2019 and June 2020. A statistically significant decrease in EIA tests occurred after March 1, 2020 (the COVID-19 peak in our region) compared to January 1, 2019–March 1, 2020 (Figure 1). After March 1, 2020, the number of EIA tests obtained decreased by 10.2 each month (95% CI, −18.7 to −1.7; P = .02). No statistically significant change in the incidence of CDI occurred. The use of antibiotics that were defined as high risk for CDI increased in the months of April–June 2020 (Figure 2). Conclusions: In this single-center study, we observed a stable incidence of CDI but decreased testing during the first peak of the COVID-19 pandemic. Understanding local HAI reporting is critical because changes in HAI reporting structures and exemptions during this period may have affected national reporting. Further research should be undertaken to investigate the effect of COVID-19 on other HAI reporting within the US healthcare system.Funding: NoDisclosures: None

Impact of Two-Step Testing Algorithm on Reducing Hospital-Onset Clostridioides difficile Infections

Clostridioides difficile infection (CDI) is one of the leading causes of hospital–onset infections. Clinically distinguishing true CDI versus colonization with C. difficile is challenging and often requires reliable and rapid molecular testing methods. At our academic center, we implemented a 2-step testing algorithm to help identify true CDI cases. The University of Mississippi Medical Center is a 700+ bed academic facility located in Jackson, Mississippi. Hospital-onset (HO) CDI was defined based on NHSN Laboratory Identified (LabID) event as the last positive C. difficile test result performed on a specimen using a multistep testing algorithm collected &gt;3 calendar days after admission to the facility. HO-CDI data were collected from all inpatient units except the NICU and newborn nursery. HO-CDI outcomes were assessed based on standardized infection ratio (SIR) data. In May 2020, we implemented a 2-step testing algorithm (Figure 1). All patients with diarrhea underwent C. difficile PCR testing. Those with positive C. difficile PCR test were reflexed to undergo enzyme immunoassay (EIA) glutamate dehydrogenase antigen (Ag) testing and toxin A and B testing. The final results were reported as colonization (C. difficile PCR+/EIA Ag+/Toxin A/B−) or true CDI case (C. difficile PCR+/EIA +/Toxin A/B +) or negative (C. difficile PCR−). All patients with colonization or true infection were placed under contact isolation precautions until diarrhea resolution for 48 hours. During the preintervention period (October 2019–April 2020), 25 HO-CDI cases were reported compared to 8 cases in the postintervention period (June 2020–December 2020). A reduction in CDI SIR occurred in the postintervention period (Q3 2020–Q4 2020, SIR 0.265) compared to preintervention period (Q4 2019–Q1 2020, SIR 0.338) (Figure 2). We successfully reduced our NHSN HO-CDI SIR below the national average after implementing a 2-step testing algorithm for CDI. The 2-step testing algorithm was useful for antimicrobial stewardship to guide appropriate CDI treatment for true cases and for infection prevention to continue isolation of infected and colonized cases to reduce the spread of C. difficile spores.Funding: NoDisclosures: None

Genomic Analysis of Clostridioides difficile in 2 Regions of the United States Reveals a Diversity of Strains and Limited Transmission.

The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole-genome sequencing across 2 Centers for Disease Control and Prevention Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community-associated (CA) and healthcare-associated (HCA) disease and assess transmission. Whole-genome sequencing was performed on C. difficile isolates from patients with CDI over 3 months between 2016 and 2017. Patients were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. CDI cases were epidemiologically classified as HCA or CA. Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were sequence type (ST) 42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), and ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%) and ST41 (77.8%). ST1 was more frequent in New York than in Minnesota (10.8% vs 3.1%). Thirty-three pairs were closely related genomically, 14 of which had potential patient-to-patient transmission supported by record review. The genomic epidemiology of C. difficile across 2 regions of the United States indicates the presence of a diverse strain profile and limited direct transmission.

Epidemiologic and Clinical Characteristics of Clostridioides difficile Infections in Hospitalized and Outpatient Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

The epidemiology and clinical course of Clostridioides difficile infection (CDI) in children, especially with cancer, are poorly defined. We aim to describe the epidemiology, clinical features and outcomes of CDI and to identify risk factors for recurrence in a pediatric oncology center. This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by positive C. difficile test in symptomatic patients. CDI episodes were classified as incident, duplicate or recurrent and community-onset, hospital-onset or community-onset healthcare facility-associated. Data about clinical course and outcomes were abstracted. Risk factors for CDI recurrence were assessed by logistic regression. One hundred seventy-eight patients 1 year of age and older developed 291 CDI episodes; 78% were incident and 22% recurrent. Underlying diagnoses were leukemia/lymphoma (57%) and solid/brain tumors (41%); 30% were HSCT recipients. Antibiotics, chemotherapy, antacids, steroids and laxatives were received by 96%, 82%, 70%, 47% and 15%, respectively. Half of the patients were neutropenic. Twenty-two percent of outpatients with CDI required hospitalization. Chemotherapy was delayed in 25%. There were no intensive care unit admissions nor deaths due to CDI. Exposure to H2-antagonists was identified as an independent risk factor for CDI recurrence. Although CDI in pediatric oncology and HSCT patients was associated with chemotherapy delay and hospitalization in approximately a quarter of patients, it was not associated with morbidity or mortality because patients had no attributable intensive care unit admission nor death. H2-antagonists are independent risk factors for CDI recurrence.

Features of Clostridioides difficile infection (CDI) in patients with cancer: A seven-year study.

e13606 Background: Clostridioides difficile infection (CDI) is frequently seen in patients with cancer. However, information of the features and clinical course of CDI in this specific setting is lacking. Our objective was to describe the clinical picture of CDI in patients with cancer and to compare it with that observed in patients without cancer. Methods: This was an observational cohort study which included all consecutive patients diagnosed of CDI at the Hospital Universitario de Valme (Sevilla, Spain) between January 2014 and October 2020. Recurrence was defined as the reappearance of symptoms of CDI with microbiologic confirmation of toxigenic Clostridioides difficile in the first 8 weeks after the end of CDI treatment according to the Infectious Diseases Society of America criteria. Results: 481 patients had a first episode of CDI during the study period, 102 (21%) had an active neoplasm at CDI diagnosis and 379 (79%) did not had history of active cancer. The proportion of CDI cases in patients with cancer among the total cases of CDI per year was: 2014: 10/70 (17%); 2015: 10/47 (21%); 2016: 17/59 (29%); 2017: 12/80 (15%); 2018: 23/82 (28%); 2019: 16/80 (20%); 2020: 14/73 (19%); p=0.3). When compared with patients without cancer, those with cancer showed differences in: age (68 [58-79] vs 77 [61-84] years; p=0.002); male sex (68 [58-79] vs 77 [61-84]; p=0.002); Charlson comorbidity index &gt; 2 (93 [92%] vs 234 [63%]; p&lt;0.001); nosocomial or healthcare related CDI (90 [88%] vs 275 [72%]; p&lt;0.001); immunosuppression (72 [70%] vs 52 [14%]; p&lt;0.001); hospitalization during the last year (78 [76%] vs 224 [59%]; p=0.001); concomitant use of proton bomb inhibitors (89 [87%] vs 265 [70%]; p=0.001) and concomitant use of antibiotics (45 [45%] vs 125 [33%]; p&lt;0.03). Regarding CDI treatment, 64 (69%), 25 (27%) and 2 (2%) patients in the cancer-group were treated with metronidazole, vancomycin and fidaxomicin, respectively, whereas the corresponding figures in non-cancer patients were 228 (67%), 102 (30%) and 5 (1.5%) (p=0.8). The proportion of oncologic patients receiving vancomycin increased after implementing an antimicrobial stewardship program focused on CDI management during 2017 (2014-2017: 2 [4%]; 2018: 3 (17%); 2019: 11 (73%); 2020: 10 (83%); p&lt;0.001). CDI recurrence could not be assessed in 23 (5%) patients who died during the first 8 weeks of follow-up for reasons other than CDI, including 8 patients with CDI and cancer. Among evaluable patients, 16 (17%) of those with cancer and 61 (17%) of those without cancer had a first CDI recurrence (p=0.9). Conclusions: CDI recurrence rates in cancer patients are similar to that observed in non-cancer patients in spite of a higher frequency of risk factors for recurrence. Appropriate CDI therapy could have counterbalanced this worse profile during recent years. Our study shows that CDI should be included among the scenarios covered by antimicrobial stewardship programs in oncologic patients.

Potent Acid Suppression With Vonoprazan vs Proton Pump Inhibitors Does Not Have Higher Association With Clostridioides difficile Infection.

Proton pump inhibitors (PPIs) are associated with the onset of Clostridioides difficile infection (CDI). Although a new potassium-competitive acid blocker, vonoprazan, consistently shows a more potent acid inhibitory effect in comparison to PPIs, the risk of CDI in vonoprazan-treated patients relative to those treated with PPIs is unknown. In this retrospective case-control study, using a nationwide hospital-based administrative database in Japan, we investigated the association of the onset of CDI in patients treated with vonoprazan. A CDI case was defined as a case in which a patient was diagnosed and treated for CDI. For each CDI case, 3 non-CDI patients were extracted as controls. Information on the usage of acid suppressants in the 2 months before the onset of CDI and other confounding factors was collected. Relative associations of gastric acid suppressants with the onset of CDI were estimated. A total of 4,466 CDI cases and 13,220 of non-CDI controls were extracted. A multivariate conditional regression analysis revealed that PPI or vonoprazan use was modestly, but significantly associated with CDI (odds ratio [95% confidence interval]: PPI, 1.3 [1.2-1.4]; vonoprazan, 1.4 [1.2-1.7]). With PPI users as a reference, vonoprazan did not show a stronger association with CDI (odds ratio [95% confidence interval]: 1.07 [0.91-1.26]). We found a significant positive association between vonoprazan use and CDI; however, the magnitude of the association was not beyond that in PPI users. This is the first report on any potential adverse effects of vonoprazan.

World Society of Emergency Surgery-American Association for the Surgery of Trauma Guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients: An executive summary.

In the last three decades, the dramatic worldwide increase in incidence and severity of Clostridioides difficile infection (CDI) (formerly Clostridium difficile infection) has made CDI a global public health challenge. Surgery is a known risk factor for development of CDI yet surgery is also a treatment option in severe cases of CDI. The World Society of Emergency Surgery guidelines for management of CDI in surgical patients were published in 2015. In 2019, the guidelines were revised and updated according to the grading of recommendations assessment, development and evaluation methodology. This executive summary is intended to consolidate knowledge on the management of CDI focusing on aspects that a general and emergency surgeon should know about the prevention and the management of CDI, by providing a practical and concise version of the original guidelines.

Changes in treatment of community-onset Clostridioides difficile infection after release of updated guidelines, Atlanta, Georgia, 2018

Updated Clostridioides difficile infection (CDI) guidelines published in 2018 recommend vancomycin as first-line treatment. Of 833 community-onset CDI cases in metropolitan Atlanta, Georgia in 2018, over half did not receive first-line treatment, although guideline adherence increased over the year. Second-line treatment was more common in patients treated in ambulatory settings.

Variants at the MHC Region Associate With Susceptibility to Clostridioides difficile Infection: A Genome-Wide Association Study Using Comprehensive Electronic Health Records

Background Clostridioides difficile is a major cause of healthcare-associated and community-acquired diarrhea. Host genetic susceptibility to Clostridioides difficile infection has not been studied on a large-scale.MethodsA total of 1,160 Clostridioides difficile infection cases and 15,304 controls were identified by applying the eMERGE Clostridioides difficile infection algorithm to electronic health record data. A genome-wide association study was performed using a linear mixed model, adjusted for significant covariates in the full dataset and the antibiotic subgroup. Colocalization and MetaXcan were performed to identify potential target genes in Clostridioides difficile infection - relevant tissue types.ResultsNo significant genome-wide association was found in the meta-analyses of the full Clostridioides difficile infection dataset. One genome-wide significant variant, rs114751021, was identified (OR = 2.42; 95%CI = 1.84-3.11; p=4.50 x 10-8) at the major histocompatibility complex region associated with Clostridioides difficile infection in the antibiotic group. Colocalization and MetaXcan identified MICA, C4A/C4B, and NOTCH4 as potential target genes. Down-regulation of MICA, upregulation of C4A and NOTCH4 was associated with a higher risk for Clostridioides difficile infection.ConclusionsLeveraging the EHR and genetic data, genome-wide association, and fine-mapping techniques, this study identified variants and genes associated with Clostridioides difficile infection, provided insights into host immune mechanisms, and described the potential for novel treatment strategies for Clostridioides difficile infection. Future replication and functional validation are needed.

Health care resource utilization and costs of recurrent Clostridioides difficile infection in the elderly: a real-world claims analysis.

BACKGROUND: Clostridioides difficile infection (CDI) affected an estimated 365,000 persons in the United States in 2017. Despite a nationally decreasing trend of CDI cases, the population incidence of recurrent CDI (rCDI) has not improved. Elderly individuals (aged ≥ 65 years) are at higher risk of CDI, rCDI, and complicated CDI compared with younger individuals. OBJECTIVE: To analyze Medicare fee-for-service data for 12 months after an initial CDI episode, in order to obtain real-world data on health care resource utilization (HRU) and costs for elderly patients with CDI and rCDI. METHODS: A retrospective cohort study of patients who were aged ≥ 65 years and had a first (index) CDI diagnosis from January 1, 2010, to December 31, 2016, and continuous enrollment in Medicare Parts A, B, and D during the 12-month pre-index and 12-month post-index periods was conducted. A CDI episode was identified by either an inpatient stay with CDI diagnosis code or an outpatient medical claim with a CDI diagnosis code plus a CDI treatment. Each CDI episode was followed by a 14-day CDI claim-free period after the last CDI claim or end of CDI treatment. rCDI was a second or subsequent episode of CDI that occurred within an 8-week window after the 14-day CDI claim-free period. The number of CDI and rCDI episodes, HRU, time to recurrence, and total all-cause direct medical costs were calculated over the 12-month pre-index (baseline) and 12-month follow-up periods and stratified by number of rCDI episodes (No rCDI, 1 rCDI, 2 rCDI, 3+ rCDI). RESULTS: A total of 268,762 patients with an index CDI were included. Mean age was 78.3 years, and 69.0% were female. HRU was higher during the 6 months immediately pre-index versus 7-12 months pre-index, including a higher proportion of patients with a hospital admission (55.1% vs. 27.5%) or emergency department visit (41.3% vs. 27.4%), respectively. Moreover, 34.7% of the study population experienced rCDI. Of those who experienced 1 recurrence, 59.1% had a second recurrence, and of those who had 2 recurrences, 58.4% had a third. During the 12-month follow-up, postacute care was used by at least 70% of each rCDI cohort. The proportion of patients with ≥ 4 hospital admissions during follow-up was highest for the 3+ rCDI cohort (24.9% of patients). During the 12-month follow-up, mean total all-cause direct costs were $76,024, $99,348, $96,148, and $96,517 for the No rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI cohorts, respectively, largely driven by inpatient costs. Adjusted all-cause total costs were significantly higher for all 3 rCDI cohorts compared with the No rCDI cohort. CONCLUSIONS: Elderly individuals experienced high rates of recurrence after their first CDI episode, and especially after a prior recurrence. The intensity of HRU during follow-up was higher for patients who suffered recurrences. Patients with rCDI had the burden of higher costs of care, including the patient out-of-pocket responsibility, versus patients with a single CDI episode. DISCLOSURES: Funding for this study was provided by Ferring Pharmaceuticals. Nelson is an employee of Ferring Pharmaceuticals, and Scott, Boules, and Unni were employees of Ferring Pharmaceuticals at the time of this study. Teigland and Parente are employees of Avalere Health and provided consulting services to Ferring Pharmaceuticals. Feuerstadt has served as a consultant to and on the speakers bureau for Merck and Co. and has served as a consultant for Ferring Pharmaceuticals and Roche Pharmaceuticals. Portions of the data contained in this study appeared as an abstract/ePoster for the AMCP Annual Meeting 2020, April 2020.

Establishment of a French surveillance system of Clostridiodes difficile infection: Comparison of patient’s characteristics with other national and European data

IntroductionThe magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies. MethodsDIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions.A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database. ResultsFrom January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%).The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study.Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies. DiscussionThese results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.

Clostridioides (Clostridium) difficile-associated diarrhea in equine in Minas Gerais, Brazil: clinical and microbiological characterization of six cases

ABSTRACT: Clostridioides (Clostridium) difficile is the main causative agent of antimicrobial-related diarrhea in humans and a major pathogen-associated enteric disorder in foals and adult horses. Moreover, studies have suggested that animals are a possible reservoir of toxigenic C. difficile strains for humans. Despite this known importance, the epidemiology of C. difficile infection (CDI) in equine is still largely unknown. Therefore, this study described six cases of equine CDI occurring in Minas Gerais, Brazil, including the characterization of the isolates. All but one equine included in this research developed CDI after antimicrobial therapy, three of which occurred during hospitalization. Coinfection with Salmonella Heidelberg and S. Infantis was detected in three cases, making the antimicrobial treatment challenging. All animals recovered after metronidazole administration. All C. difficile isolates were susceptible to metronidazole and vancomycin, while three were resistant to moxifloxacin and two were resistant to clindamycin. The isolates were classified as RT126 (n = 4), RT078 (n = 1), and RT014/020 (n = 1), all previously reported infecting humans and animals worldwide.