Clostridioides Difficile Infection Testing Research Articles

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.

High Prevalence of Multistep Algorithms in Diagnostic Clostridioides difficile Laboratory Testing.

Laboratory testing practices for diagnosis of Clostridioides difficile infection (CDI) have evolved in response to published guidelines, availability of highly sensitive nucleic acid amplification tests (NAATs), perceived problems with the specificity of NAATs, and CDI reporting requirements. To assess the current state of laboratory practice for diagnostic CDI testing. An optional 8-item supplemental questionnaire was distributed in December 2019 to the 1374 laboratories participating in the College of American Pathologists C difficile Detection (CDF) proficiency testing program challenge CDF-C. Of 1374 CDF-C participants, 1160 (84.4%) responded, predominantly representing laboratories based in the United States (1077 of 1160; 92.8%). The majority reported using a multistep testing algorithm (684 of 1159; 59.0%). Initial testing with a glutamate dehydrogenase and toxin A/B combination test followed by NAAT for discrepant results was the most common testing method (360 of 1146; 31.4%). NAAT alone (299 of 1146; 26.1%) was next, then NAAT followed by an assay that included toxin A/B enzyme immunoassay if NAAT is positive (258 of 1146; 22.5%). Only 5.4% (62 of 1146) reported using toxin A/B immunoassay alone. Most respondents (1093 of 1131; 96.6%) reported rejecting CDI tests on formed stool, but rejection of CDI testing in pediatric patients was uncommon (211 of 1131; 18.7%). Rejection of CDI testing in patients using laxatives was reported more often by US-based respondents (379 of 1054 [36.0%] versus 9 of 77 [11.7%], P < .001). Multistep algorithms for CDI diagnosis are widely used in line with published recommendations. Most respondents reported rejection of formed stool for CDI testing, but few reported rejection of testing in infants and patients taking laxatives, suggesting these may be areas of opportunity for laboratories to pursue in improving CDI testing practices.

High Prevalence of Laxative Use Among Those Tested for Clostridioides difficile Infection in VA Hospitals

Background: Clostridioides difficile infection (CDI) is associated with 500,000 infections and 30,000 deaths per year. Inappropriate testing and treatment of patients with asymptomatic colonization occurs frequently (between 15% and 41%). The VA CDI guidelines emphasize avoidance of CDI testing in patients with laxative use within the previous 48 hours due to the high likelihood of non-infectious diarrhea. The objective of this study was to assess laxative administration among inpatients tested for CDI in VA hospitals and identify factors associated with guideline discordance. Methods: Adults hospitalized in Illinois, Wisconsin, and Michigan VA Medical Centers from January 2019-December 2022 with a CDI test performed during the admission were included. CDI tests included Toxin B gene Polymerase Chain Reaction or Toxin Enzyme Immunoassay. Tests were defined as positive, negative, or cancelled according to the diagnostic protocols of the VA testing laboratories. Laxative use, patient demographics, admission data, and comorbidities were collected from the VA Corporate Data Warehouse. Guideline discordant testing was defined as a diagnostic test for CDI ordered within 48 hours of a recorded laxative dose. Factors associated with discordant testing were analyzed using clustered binomial logistic regression models. Analyses were completed using SAS 9.4. Results: There were 7,326 tests ordered for 4,888 patients during the study. Patients were predominantly White (61.8%), male (95.6%), and elderly (mean age=70.0 standard deviation=12.1). Most (59.0%) patients had received at least one dose of laxative in the 48 hours preceding their CDI test. Being Black (Odds Ratio (OR)=0.86 (95%Confidence Interval (95%CI) =0.76,0.98) or Hispanic (OR (95%CI) =0.62(0.48,0.82) vs White) was associated with a decreased likelihood of inappropriate testing due to recent laxative use. Being tested at a rural facility (OR (95%CI) =1.23 (1.07,1.41) vs urban), within a long-term care (LTC) unit (OR (95%CI) =1.67 (1.41,1.97) vs inpatient), or within an intensive care unit (ICU) (OR (95%CI) =1.40 (1.24,1.59)) were all associated with an increased likelihood of being inappropriately tested. Guideline discordant tests were more likely to have negative results (OR (95%CI) =1.25 (1.05,1.49)) compared to guideline concordant tests. Discussion: Laxative administration in the 48 hours preceding CDI testing was common among hospitalized Veterans and associated with a lower likelihood of positive Results: This echoes non-VA studies where laxative use was reported at 44%. An increased likelihood of guideline discordant testing in ICU and LTC settings suggests the need for greater diagnostic stewardship interventions. Additionally, further work to determine negative outcomes associated with inappropriate testing are needed.

Comparison of Medicare Claims-based Clostridioides difficile infection classification to chart review using a linked cohort

Background: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. Categorizing CDI based on location of onset and potential exposure is critical in understanding transmission patterns and prevention strategies. While claims data are well-suited for identifying prior healthcare utilization exposures, they lack specimen collection and diagnosis dates to assign likely location of onset. Algorithms to classify CDI onset and healthcare association using claims data have been published, but the degree of misclassification is unknown. Methods: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016-2020 to Medicare beneficiaries using residence, birth date, sex, and hospitalization and/or healthcare exposure dates. Uniquely linked patients with fee-for-service Medicare A/B coverage and complete EIP case report forms were included. Patients with a claims CDI diagnosis code within ±28 days of a positive CDI test reported to EIP were categorized as hospital-onset (HO), long-term care facility onset (LTCFO), or community-onset (CO, either healthcare facility-associated [COHCFA] or community-associated [CA]) using a previously published algorithm based on claim type, ICD-10-CM code position, and duration of hospitalization (if applicable). EIP classifies CDI into these categories using positive specimen collection date and other information from chart review (e.g. admit/discharge dates). We assessed concordance of EIP and claims case classifications using Cohen’s kappa. Results: Of 10,002 eligible EIP-identified CDI cases, 7,064 were linked to a unique beneficiary; 3,451 met Medicare A/B fee-for-service coverage inclusion criteria. Of these, 650 (19%) did not have a claims diagnosis code ±28 days of the EIP specimen collection date (Table); 48% (313/650) of those without a claims diagnosis code were categorized by EIP as CA CDI. Among those with a CDI diagnosis code, concurrence of claims-based and EIP CDI classification was 68% (κ=0.56). Concurrence was highest for HO and lowest for COHCFA CDI. A substantial number of EIP-classified CO CDIs (30%, Figure) were misclassified as HO using the claims-based algorithm; half of these had a primary ICD-10 diagnosis code of sepsis (226/454; 50%). Conclusions: Evidence of CDI in claims data was found for 81% of EIP-reported CDI cases. Medicare classification algorithms concurred with the EIP classification in 68% of cases. Discordance was most common for community-onset CDI patients, many of whom were hospitalized with a primary diagnosis of sepsis. Misclassification of CO-CDI as HO may bias findings of claims-based CDI studies.

Clostridioides difficile infection in patients with and without COVID-19 during the pandemic: A retrospective cohort study from a tertiary referral hospital

ObjectivesThis study aims to detect the prevalence and specific characteristics of Clostridioides difficile infection (CDI) during the COVID-19 pandemic. MethodsIn this retrospective observational study, conducted in a tertiary hospital in Greece between May 2021 and October 2022, patients with CDI from COVID-19 and Internal Medicine wards were enrolled and compared based on epidemiological and disease-associated data. ResultsIn total, 4322 patients were admitted, and 435 samples for CDI were analyzed, with 104/435 (23.9 %) sample positivity and 2.4 % prevalence. We observed an increased prevalence of CDI compared to the beginning of the COVID-19 pandemic (prevalence = 1.7 %, p = 0.003). 35.6 % of the CDI patients were hospitalized in the COVID-19 ward and 64.4 % in the Internal Medicine ward. COVID-19 patients were younger (p = 0.02) with a lower Charlson Comorbidity Index (CCI) compared to the Internal Medicine ward patients (p < 0.001). With regards to the origin of CDI cases, in the Internal Medicine ward, 68.7 % presented with Hospital-Onset CDI, 17.9 % with Community Onset-Healthcare Associated CDI and 13.4 % with Community Associated CDI, while in the COVID-19 ward, the respective percentages were 86.5 %, 5.4 % and 8.1 %. Finally, there was an increased CDI-related CFR (Case Fatality Ratio) in the Internal Medicine ward compared to the COVID-19 ward (28.4 % vs. 5.4 %, p = 0.001). ConclusionsIncreased CDI prevalence and testing were observed compared to the beginning of the COVID-19 pandemic. Lower CDI-related CFR was observed in patients with COVID-19, which may be credited to the patients’ significantly lower median age and CCI, as well as to the majority of deaths being due to respiratory failure.

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

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

Laboratory diagnosis of Clostridioides difficile infection: guidelines and status of practice in Korea

Clostridioides difficile infection (CDI) is a common healthcare-associated infection that is expected to increase with the increases in the elderly population, immunocompromised patients treated with chemotherapy and immunosuppressive drugs, antimicrobial-resistant bacteria, and invasive medical technologies. Accurate diagnosis is critical for proper treatment and management of CDI. Clinical laboratories typically use four methods to diagnose CDI: C. difficile culture, toxin detection using immunoassays, detection of glutamate dehydrogenase using immunoassays, and detection of toxin A/B gene. Each CDI diagnostic test has strengths and limitations, and varies in performance. Guidelines for CDI diagnosis have been developed by organizations that include the European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America/Society for Healthcare Epidemiology of America, and American College of Gastroenterology. Certain other countries have guidelines. In Korea, surveys on CDI diagnosis performed in 2015 and 2018 revealed a shift in CDI testing in clinical laboratories in Korea. It is necessary to develop standardized diagnostic guidelines for CDI appropriate for the Korean context.

Burden of Medically Attended Diarrhea and Outpatient Clostridioides difficile Infection Among Persons in 2 Large Integrated Healthcare Settings, 2016-2021.

Identification of Clostridioides difficile infection (CDI) in the community setting is increasing. We describe testing for CDI among patients with medically attended diarrhea (MAD) in the outpatient setting, and the incidence of outpatient CDI. This was a retrospective cohort study among members ≥18 years of age from Kaiser Permanente Southern California and Kaiser Permanente Northwest from 1 January 2016 through 31 December 2021. MAD was identified by outpatient diarrheal International Classification of Diseases, Tenth Revision diagnosis codes, and CDI through positive laboratory results. Outpatient CDI was defined by no hospitalization ≤7 days after specimen collection. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables. Outpatient CDI burden 12 months following index date was measured by CDI-associated healthcare visits, and CDI testing and treatment. We identified 777 533 MAD episodes; 12.1% (93 964/777 533) were tested for CDI. Of those tested, 10.8% (10 110/93 964) were positive. Outpatient CDI IR was 51.0 (95% confidence interval [CI], 49.8-52.2) per 100 000 person-years, decreasing from 58.2 (95% CI, 55.7-60.7) in 2016 to 45.7 (95% CI, 43.7-47.8) in 2021. Approximately 44% (n = 4200) received an antibiotic 30 days prior to index date and 84.1% (n = 8006) CDIs were "community-associated" (no hospitalizations 12 weeks prior to index date). Of outpatient CDIs, 6.7% (n = 526) had a CDI-associated hospitalization ≤12 months. There was a high incidence of outpatient CDI despite infrequent CDI testing among patients with MAD. The majority of those with outpatient CDI had no recent antibiotic use and no recent hospitalization. Further studies are needed to understand the source and management of medically attended outpatient CDI.

Informing estimates of probability of Clostridioides difficile infection for testing and treatment: expert consensus from a modified-Delphi procedure

Abstract Background: Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI. Methods: A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by &gt;70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey. Results: All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (&gt;70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey). Conclusion: Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.

Diagnostic Guidance for C. difficile Infections.

Diagnosis of Clostridioides difficile infection (CDI) can be challenging. First of all, there has been debate on which of the two reference assays, cell cytotoxicity neutralization assay (CCNA) or toxigenic culture (TC), should be considered the gold standard for CDI detection. Although the CCNA suffers most from suboptimal storage conditions and subsequent toxin degradation, TC is reported to falsely increase CDI detection rates as it cannot differentiate CDI patients from patients asymptomatically colonised by toxigenic C. difficile. Several rapid assays are available for CDI detection and fall into three broad categories: (1) enzyme immunoassays for glutamate dehydrogenase, (2) enzyme immunoassays or single-molecule array assays for toxins A/B and (3) nucleic acid amplification tests detecting toxin genes. All three categories have their own limitations, being suboptimal specificity and/or sensitivity or the inability to discern colonised patients from CDI patients. In light of these limitations, multi-step algorithmic testing has been advocated by international guidelines (IDSA/SHEA and ESCMID) in order to optimize diagnostic accuracy. As a result, a survey performed in 2018-2019 in Europe revealed that most of all hospital sites reported using more than one test to diagnose CDI. CDI incidence rates are also influenced by sample selection criteria, as several studies have shown that if not all unformed stool samples are tested for CDI, many cases may be missed due to an absence of clinical suspicion. Since methods for diagnosing CDI remain imperfect, there has been a growing interest in alternative testing strategies like faecal microbiota biomarkers, immune modulating interleukins, cytokines and imaging methods. At the moment, these alternative methods might play an adjunctive role, but they are not suitable to replace conventional CDI testing strategies.

Clostridioides difficile infection in neurosurgical patients in a national centre over 10 years: less common but associated with longer hospital stays.

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea, contributing to patient morbidity and prolonged length-of-stay (LOS). We retrospectively assessed CDI over a decade in a national neurosurgical centre, with a multi-disciplinary approach to CDI surveillance and antimicrobial stewardship, by comparing CDI patients with other patient groups. Data on CDI in neurosurgical inpatients between January 2012 and December 2021 were collated. Disease-specific variables were compared to other inpatients with CDI. Rates per 10,000 bed days used were calculated. Patient-specific differences were compared with neurosurgical patients without CDI. CDI rates by patient group were explored using odds ratio (OR) and χ2 analyses. Negative binomial regression was used to investigate CDI rates over time. Of 50 neurosurgical patients with CDI, all were HA; the average age was 53 years (standard deviation (SD) 16.3 years), 49 were first-episode CDI, and three had severe CDI. The majority (76.7%) had received recent antimicrobials. Compared with non-neurosurgical CDI patients, neurosurgical CDI rates differed significantly (1.9 versus 3.6 per 10,000 bed days used, p < 0.05), neurosurgical patients were younger (p ≤ 0.01), C. difficile testing was more likely to be requested by neurosurgeons (OR 2.4; p ≤ 0.01), and the proportion of severe CDI was higher (6% versus 2%, OR 3.0, p = 0.07, confidence interval (CI) 0.54 to 11.3). Within the neurosurgical cohort, CDI patients had an average LOS four times that of other patients (CI 15.2 to 35.1; p < 0.01) and were older (53.5 versus 47.8 years, CI 0.1 to 11 years; p < 0.05). Only one CDI outbreak was linked to neurosurgical patients. CDI in neurosurgery patients differed from the wider hospital, with greater awareness of CDI testing. Longer LOS impacted bed utilisation with limited capacity. Robust surveillance supports proactive antimicrobial stewardship programmes in this vulnerable population.

A survey of physicians’ perceptions of diagnostic tests for Clostridioides difficile infection

Background: This study aimed to investigate perceptions of Clostridioides difficile infection (CDI) diagnostic tests among physicians who prescribe CDI diagnostic tests as part of providing direct patient care. Methods: In August 2018, we provided a 12-question survey of gastroenterologists (the most common referral source for CDI testing) to 35 medical institutions in Korea, asking them about their perceptions of CDI diagnosis and testing. Results: A comparison of the perceptions of physicians and clinical pathologists (CPs) found that physicians had a lower perceived sensitivity of the toxin AB enzyme immunoassay test. For nucleic acid amplification tests, physicians exhibited a perception of higher assay sensitivity and specificity than CPs. The specificity of culture tests was generally perceived as high by physicians, whereas CPs regarding expressed mixed opinions. All but one physician and one CPs found the algorithmic test useful. Concerning the CDI isolation criteria, physicians commenced patient isolation by concurrently assessing both test results and clinical symptoms, rather than exclusively relying upon test results. Among CPs, 84.6% said they could rely on symptoms to determine when to release a patient from isolation, while 46.2% of physicians said they would rely on test results. Conclusion: This study provides useful information on the status of laboratory diagnosis of CDI in Korea and what needs to be improved, which will help to standardize and improve laboratory diagnosis of CDI in Korea.

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.

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

Utilization of a novel humble inquiry interview approach in assessing implementation barriers to a nurse-driven Clostridioides difficile test order set

Hospital onset Clostridioides difficile infection (CDI) causes significant disease burden and is associated with increased patient mortality. A nurse-driven CDI test order set had been implemented to reduce hospital-onset CDI, yet the order set was not being used. We employed a humble inquiry interview method to identify barriers to using the CDI test order set. The humble inquiry approach uncovered unexpected barriers and may be a robust method to identify additional infection prevention evidence-to-practice gaps.

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.

Impact of testing on Clostridioides difficile infection in hospitals across Europe: a mathematical model

ObjectivesThe prevalence of Clostridioides difficile infection (CDI) has been shown to vary markedly between European countries, both in hospitals and in the community. Determining the true prevalence has proven challenging. Without systematic testing in hospitals, the unchecked transmission of CDI can lead to large outbreaks in more susceptible cohorts.We investigate the success of CDI surveillance and control measures across Europe, by examining the dynamics of disease spread from the community into a hospital setting. We focus on national differences, such as variability in testing and sampling, disease prevalence in communities and hospitals, and antimicrobial usage. MethodsWe developed a stochastic, compartmental, dynamic mathematical model parameterized using sampling and testing rate data from COMBACTE-CDI, a multicountry study in which all diarrhoeal stool samples (N = 3163) from European laboratories were tested for CDI, and data for antimicrobial usage and incidence of hospital cases sourced from the European Centre for Disease Prevention and Control. ResultsThe framework estimates the prevalence of CDI among hospital patients across European countries and explores how national differences impact the dynamics, transmission, and relative incidence of CDI within the hospital setting. The model illustrates the mechanisms influencing these national differences, namely, antimicrobial usage rates, national sampling and testing rates, and community prevalence of CDI. DiscussionDifferential costs for testing and practicalities of scaling up testing mean every country needs to consider balancing CDI testing costs against the costs of treatment and care of patients with CDI.

A Predictive Model to Identify Complicated Clostridiodes difficile Infection.

Clostridioides difficile infection (CDI) is a leading cause of health care-associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI. We conducted a multicenter retrospective cohort study of adults diagnosed with CDI. After randomly partitioning the data into training and validation sets, we developed and compared 3 machine learning algorithms (lasso regression, random forest, stacked ensemble) with 10-fold cross-validation to predict disease-related complications (intensive care unit admission, colectomy, or death attributable to CDI) within 30 days of diagnosis. Model performance was assessed using the area under the receiver operating curve (AUC). A total of 3646 patients with CDI were included, of whom 217 (6%) had complications. All 3 models performed well (AUC, 0.88-0.89). Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, non-CDI-related intensive care unit admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach. However, race was an important modifier, with models showing worse performance in non-White patients. Using a large heterogeneous population of patients, we developed and validated a prediction model that estimates risk for complications from CDI with good accuracy. Future studies should aim to reduce the disparity in model accuracy between White and non-White patients and to improve performance overall.

389. Epidemiology of Multiple Recurrent Clostridioides difficile in the Atlanta Metropolitan Area between 2016 and 2019

Abstract Background Patients with multiple recurrences of Clostridioides difficile infection (CDI) have longer hospital stays and lower quality of life. Recent changes in therapies and strains of CDI make understanding recurrent CDI in the general population critical as these patients may benefit from microbiota restoring therapies rather than antibiotics alone. Methods Georgia’s Emerging Infections Program (supported by CDC) conducts CDI surveillance in 8 counties around metropolitan Atlanta, GA (population ∼4 million). CDI is defined as any C. difficile-positive specimen with no positive test in the prior 2 weeks. We evaluated CDI between Jan 2015 through Dec 2019 and captured recurrent CDI (CDI test date 2-52 weeks following previous CDI) for 2016-2019 which were categorized as single episode only, recurrent (2 episodes ≤ 1 year) or multiple recurrent (&amp;gt;2 episodes ≤ 1 year). Year was attributed to date of final episode. Census data was used to determine crude and age-specific incidence. Bivariate and multivariable logistic regression was used to estimate odds for multiple recurrent compared to single recurrent CDI with demographic, comorbidity and treatment related covariates. Results Over 4 years 13,745 patients had at least one episode of CDI, 2,930 (20%) had ≥ 1 recurrence and 916 (30%) of these progressed to multiple recurrence. Between 2016 to 2019, incidence of single CDI decreased 25% from 93/100,000 to 69/100,000 (P&amp;lt; 0.01). Multiple recurrent CDI decreased 45% from 9/100,000 to 5/100,000) (P&amp;lt; 0.01); incidence in the 80+ age group was highest and where decreased incidence was most dramatic during the study period (Figures). Time between 1st and 2nd episode was longer among patients with single recurrent than multiple recurrent CDI (median 12 weeks vs. 9 weeks, P&amp;lt; 0.01).. Independent predictors of multiple recurrence were fewer days (&amp;lt; 90) between episodes (aOR: 1.87 P&amp;lt; 0.01) and chronic renal disease (aOR: 1.59 , P&amp;lt; 0.01). Figure 1:Annual Incidence of CDI by age group. A) Incidence of CDI among patients with only a single episode of CDI within 365 days. B) Incidence of CDI among patients with three or more episodes (two or more recurrence) within 365 days. RR documented compares 2016 to 2018 incidence in the 80+ age group Conclusion Time between 1st and 2nd CDI most strongly predicts likelihood of progression to multiple recurrences. Of all measured comorbid conditions, renal disease was most predictive. These findings may help to identify patients at high risk for progression for advanced interventions such as microbiota modifying therapies. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support Colleen Kraft, MD MS, Rebiotix Inc: Advisor/Consultant|SERES: Advisor/Consultant.

Molecular epidemiology and clinical characteristics of Clostridioides difficile infection in patients with inflammatory bowel disease from a teaching hospital.

Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is of increasing concern. This study aimed to investigate the molecular epidemiology and antimicrobial susceptibilities of toxigenic C. difficile isolated from IBD patients and to evaluate the risk factors for CDI in IBD population. Loose or watery stools from IBD patients were tested for glutamate dehydrogenase, C. difficile toxins A&B and anaerobic culture. Toxigenic C. difficile isolates were characterized by multi-locus sequence typing, ribotyping and antimicrobial susceptibility testing. The prevalence of CDI in IBD patients was 13.6% (43/317). The dominant sequence types (STs) were ST35 (20.9%), ST2 (18.6%) and ST37 (16.3%). The most common ribotypes (RTs) were RT 017 (18.6%), RT 012 (14.0%), and RT 220 (14.0%), whereas RT 027 and RT 078 were not detected in this study. All the isolates were susceptible to vancomycin and metronidazole. The multidrug resistance rate of C. difficile RT 017 was higher (p < 0.01) than that of other RT strains. Recent hospitalization, use of corticosteroids and proton pump inhibitors were related to increased risk of CDI in IBD patients; of these, recent hospitalization and proton pump inhibitors use were independent risk factors. Patients with IBD have a relatively high incidence rate of CDI. C. difficile RT 017 is most frequently isolated from IBD patients in this region and warrants more attention to its high resistance rate. Clinicians should pay greater attention to CDI testing in IBD patients with diarrhea to ensure early diagnosis and initiation of effective treatment.