Difficile Stool Research Articles

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples

PurposeThe clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI.MethodsAll stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared.ResultsAmong 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96–0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16–0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7–21 days without complication.ConclusionOur study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

A Multimodal Intervention to Reduce C. difficile Infections and Stool Testing.

The introduction of multiplex gastrointestinal panels at our institution resulted in increased Clostridioides difficile (C. difficile) detection and stool test utilization. We aimed to reduce hospital-onset C. difficile infections (HO-CDIs), C. difficile detection, and overall stool testing by 20% within 1 year. We conducted a quality improvement project from 2018 to 2020 at a large children's hospital. Interventions included development of a C. difficile testing and treatment clinical care pathway, new options for gastrointestinal panel testing with or without C. difficile (results were suppressed if not ordered), clinical decision support tool to restrict testing, and targeted prevention efforts. Outcomes included the rate of HO-CDI (primary), C. difficile detection, and overall stool testing. All measures were evaluated monthly among hospitalized children per 10 000 patient-days (PDs) using statistical process-control charts. For balancing measures, we tracked suppressed C. difficile results that were released during real-time monitoring because of concern for true infection and C. difficile-related adverse events. HO-CDI decreased by 55%, from 11 to 5 per 10 000 PDs. C. difficile detection decreased by 44%, from 18 to 10 per 10 000 PDs, and overall test utilization decreased by 29%, from 99 to 70 per 10 000 PDs. The decrease in stool tests resulted in annual savings of $55 649. Only 2.3% of initially suppressed positive C. difficile results were released, and no patients had adverse events. Diagnostic stewardship strategies, coupled with an evidence-based clinical care pathway, can be used to decrease C. difficile and improve overall test utilization.

Fungal and bacterial gut microbiota differ between Clostridioides difficile colonization and infection.

Aim: The bacterial microbiota is well-recognized for its role in Clostridioides difficile colonization and infection, while fungi and yeasts remain understudied. The aim of this study was to analyze the predictive value of the mycobiota and its interactions with the bacterial microbiota in light of C. difficile colonization and infection. Methods: The mycobiota was profiled by ITS2 sequencing of fecal DNA from C. difficile infection (CDI) patients (n = 29), asymptomatically C. difficile colonization (CDC) patients (n = 38), and hospitalized controls with C. difficile negative stool culture (controls; n = 38). Previously published 16S rRNA gene sequencing data of the same cohort were used additionally for machine learning and fungal-bacterial network analysis. Results: CDI patients were characterized by a significantly higher abundance of Candida spp. (MD 0.270 ± 0.089, P = 0.002) and Candida albicans (MD 0.165 ± 0.082, P = 0.023) compared to controls. Additionally, they were deprived of Aspergillus spp. (MD -0.067 ± 0.026, P = 0.000) and Penicillium spp. (MD -0.118 ± 0.043, P = 0.000) compared to CDC patients. Network analysis revealed a positive association between several fungi and bacteria in CDI and CDC, although the analysis did not reveal a direct association between Clostridioides spp. and fungi. Furthermore, the microbiota machine learning model outperformed the models based on the mycobiota and the joint microbiota-mycobiota model. The microbiota classifier successfully distinguished CDI from CDC [Area Under the Receiver Operating Characteristic (AUROC) = 0.884] and CDI from controls (AUROC = 0.905). Blautia and Bifidobacterium were marker genera associated with CDC patients and controls. Conclusion: The gut mycobiota differs between CDI, CDC, and controls and may affect Clostridioides spp. through indirect interactions. The mycobiota data alone could not successfully discriminate CDC from controls or CDI patients and did not have additional predictive value to the bacterial microbiota data. The identification of bacterial marker genera associated with CDC and controls warrants further investigation.

595. Recovery of Clostridioides difficile Isolates from Cary-Blair Transport Medium Compared to No Transport Medium

Abstract Background Surveillance of C. difficile infection (CDI), one of the most common U.S. healthcare-associated infections, is essential to inform public health response, characterize strains causing disease, and describe changes in strain prevalence over time. The U.S. CDC’s Emerging Infections Program (EIP) has conducted active CDI surveillance, including culturing of C. difficile from a convenience sample of stool samples from cases, since 2009. Cary-Blair transport medium (CBTM) is used by some clinical laboratories for stool testing, but little is known about its impact on the recovery of C. difficile from culture. Methods We performed a cross-sectional study of the recovery of C. difficile isolates from C. difficile positive stools received 10/2021 – 10/2022 from Colorado and Georgia EIP sites. Stools were collected and stored within CBTM or within no transport medium per site protocols and subsequently frozen. Frozen samples were thawed and inoculated on taurocholate-cycloserine-cefoxitin-fructose agar plates (TCCFA) for recovery. Specimens from which C. difficile was not recovered on TCCFA plates were subjected to alcohol shock to enhance the recovery rates. We compared the recovery rates of C. difficile from stools in CBTM and stools in no transport medium. Results We cultured 825 stools from Colorado and Georgia, recovering C. difficile from 81.5% of stools. Overall, 412 (49.9%) stools were in CBTM and 413 (50.1%) were stools in no transport medium. Of those with known testing data, 410/410 (100%) CBTM stools vs 371/407 (91.2%) non-CBTM stools were C. difficile positive by PCR test (p&amp;lt; 0.01). Colorado stools accounted for 78% of the CBTM specimens. We recovered C. difficile on TCCFA plates from 59% (244/412) of stools in CBTM compared to 84% (348/413) in no transport medium (p&amp;lt; 0.01). After including alcohol shock results, C. difficile was recovered from 72% of CBTM stools, and 91% from stools in no medium (p&amp;lt; 0.01). Conclusion Cary-Blair transport medium may limit the recovery of C. difficile from culture and impact the ability to detect emerging strains. A large parallel study is needed to determine if these findings are reproducible and if stool collection methods should be standardized to maximize the recoverability of C. difficile by culture. Disclosures Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria Dale N. Gerding, MD, Destiny Pharma,: Advisor/Consultant|Sebela Pharma: Advisor/Consultant

691. Association between Clostridioides difficile Colonization, Rectal Swab NAAT Positivity, and Environmental Contamination

Abstract Background Clostridioides difficile (CD) colonization is common among hospitalized patients. Screening for toxigenic CD (TCD) colonization with rectal swab nucleic acid amplification tests (NAAT) may identify people at risk for CDI and help prevent onward TCD transmission, especially in immunocompromised patients with long hospitalizations. The study objective was to test whether rectal swab NAAT could detect TCD colonized patients and whether NAAT results identify patients that contribute to environmental contamination. Methods This was a prospective cohort study on two BMT/Leukemia units. Stool specimens, rectal swabs, and environmental swabs (bedrail, room sink, keyboard) were collected from patients at admission and weekly and cultured semi-quantitatively for TCD. NAAT (Cepheid) was performed on rectal swabs (eSwabs; Copan Diagnostics). The relationship between stool TCD concentration, NAAT Ct, and a positive environmental culture was evaluated using univariate logistic regression. Bleach was used for daily and terminal discharge cleaning of all rooms. Toxigenicity was determined by detection of tcdA or tcdB by whole genome sequencing (WGS). Results From January 2019 - July 2019, 659 stool specimens and 495 rectal swabs were collected from 384 patients. Specimens from 554 patient-days were cultured and 126 (23%) were positive. Of those, 88 (70%) were TCD. 21 of 987 (2%) environmental swabs were TCD positive; 18 (86%) were from bedrails. Among 61 unique patient calendar days with paired rectal swab NAAT and stool culture results (paired samples), overall sensitivity of rectal swab NAAT to detect toxigenic CD colonization compared to culture was 44%, with 4/16 (25%) of people colonized with &amp;gt; 0 - &amp;lt; 10,000 CFU/g of TCD and 7/9 (78%) with ≥ 10,000 CFU/g TCD (Figure 1). There was no relationship between stool culture or rectal swab NAAT result and risk of a positive environmental swab (Figure 2). Figure 1. Toxigenic C. difficile semi-quantitative culture and rectal swab NAAT on paired patient-day of specimen collection (N=61 patient-days) Figure 2. Toxigenic C. difficile semi-quantitative stool and rectal swab NAAT results and environmental contamination by paired patient-day of specimen collection Conclusion Rectal swab NAAT may not be sufficiently sensitive to screen for TCD colonization that contributes to environmental contamination. Disclosures Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Grant/Research Support|Merck and Co.: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres Therapeutics: Advisor/Consultant|Summit: Advisor/Consultant|Theriva Biologics: Grant/Research Support

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial.

Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking. To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics. Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed. Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8). Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo. EudraCT 2017-002418-30.

A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

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.

Incidence and Risk Factors for Antibiotic-associated Diarrhea Among Hospitalized Children.

We aimed to evaluate the incidence, clinical findings, and risk factors of antibiotic-associated diarrhea (AAD) in hospitalized children without known comorbid diseases. All hospitalized children during the 1-year period that fulfilled the inclusion criteria were included in this study (n = 358). AAD was defined as; ≥2 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment caused by Clostridioides difficile or negative stool tests for identifiable infectious agents. During hospitalization, diarrhea developed in 32 (8.93%) of the 358 patients. C. difficile toxin B was positive for 1 case. No infectious agents were detected in 21 patients. Overall, AAD was observed in 22 patients (6.14%, 95% CI: 4.09-9.13). Male sex ( P = 0.027, OR: 3.36), age between 1 month and <3 years ( P = 0.01, OR: 4.23), ibuprofen use ( P = 0.044, OR: 2.63) and late administration of antibiotics ( P = 0.001, OR: 9.5) were associated with the development of AAD. The incidence of AAD is low among hospitalized children without comorbid diseases, and most diarrheal episodes are mild and self-limiting. The use of probiotics in this patient group may be limited to certain specific situations.

An Algorithm Addressing the Problem of Overdiagnosis of Clostridioides difficile Infections in Hematopoietic Stem Cell Transplantation Recipients: Effects on C. difficile Infection Rates and Patient Outcomes

Diarrhea of other causes and Clostridioides difficile colonization are common in patients hospitalized for hematopoietic stem cell transplantation (HSCT). It has been well recognized that these issues tend to decrease the specificity of stool testing for C. difficile infection (CDI). The best way to address this problem is uncertain. In September 2018, we initiated a project with the goal of addressing the apparent problem of overdiagnosis of CDIs in our HSCT population. Using the quality improvement tool Model for Improvement, we introduced a C. difficile stool testing and CDI diagnosis algorithm with the aim of decreasing unnecessary inpatient CDI diagnoses and treatments. In this study, we examined the effects of the algorithm. We reviewed all HSCT admissions for the 2 years before introduction of the algorithm and the subsequent 3 years, recording all stool submissions for C. difficile determination and CDI. At the close of the study, we recruited our advanced practice providers (APPs) to review all CDIs following algorithm initiation and provide feedback on the ease of use of the algorithm and potential improvements to the overall process. Stool submissions for C. difficile determination decreased from 38.0/1000 to 20.6/1000 inpatient days (P < .001) and CDI diagnoses decreased from 5.5/1000 to 2.4/1000 days (P=.007). Patients admitted for a first allogeneic HSCT, first autologous HSCT, or HSCT readmission showed similar proportionate reductions. No detrimental effects on hospital length of stay, overall survival, progression-free survival, rate of readmission post-HSCT, incidence of acute graft-versus-host disease, or incidence of recurrent CDI were noted following algorithm introduction. A strategy of education, monitoring/feedback, and ease of algorithm access proved effective in inducing provider compliance. APPs rated the algorithm high on ease of use. We conclude that the use of an algorithm defining criteria for C. difficile testing, diagnosis, and treatment was associated with significantly decreased CDI diagnoses on a HSCT inpatient unit without apparent adverse effects.

Preservation of the Innate Immune Response to Clostridioides difficile Infection in Hospitalized Immunocompromised Patients.

Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-10, IL-15, IL-1β, IL-4, IL-6, IL-8, and tumor necrosis factor-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1β and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1β demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients.

Incidental Detection of Pseudomembranous Colitis Through 18F-FDG PET/CT During the Restaging of Colorectal Cancer.

A 59-year-old man, previously submitted to anterior resection due to rectal cancer, underwent a contrast-enhanced computed tomography (ce-CT) for restaging before eventual chemotherapy. Because ce-CT showed a moderate enlargement of the descending colonic lumen, in despite the lack of symptoms, positron emission tomography (PET)/CT 18F-fluorodeoxyglucose (FDG) was carried out. 18F-FDG PET/CT demonstrated highly increased tracer incorporation along the colon walls. Two days after the PET/CT examination, complaints of diarrhea and abdominal pain began. Clostridioides difficile stool test resulted positiv; thus, thus he started antibiotic therapy without benefit. Because follow-up ce-CT demonstrated a megacolon condition, he was submitted to hemicolectomy. Histology revealed a diffuse condition of pseudomembranous colitis (PMC). This case highlights the potential of 18F-FDG PET/CT for detecting PMC morphological and functional features also in pre-symptomatic patients.

1669. A US Based National Surveillance Study for the Susceptibility and Epidemiology of Clostridioides difficile Associated Diarrheal Isolates with Special Reference to Ridinilazole: 2020-2021

Abstract Background We have previously reported on a US based national surveillance study from 6 geographically dispersed medical centers for the susceptibility and epidemiology of C. difficile isolates. This current survey was conducted with isolates collected in 2020-21 with specific attention to the susceptibility to ridinilazole as well as nine comparators. A summary of the susceptibilities of 300 isolates of C. difficile tested against 10 antimicrobial agents Methods in 2020-21 C. difficile isolates or stools from patients with C. difficile toxin positive antibiotic associated diarrhea were collected in 6 US medical centers and referred to a central lab. After confirmation of 300 isolates antibiotic susceptibilities were determined by agar dilution method (CLSI M11-A9) against 10 agents listed in Table below. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Results A summary of the susceptibilities of the 300 isolates against 10 antimicrobial agents are shown in the Table. The most common ribotype was 014-020 (14.4% compared to 11.8% in 2016), followed by 106 (10%, compared to 15% in 2016), 027 (10% compared to 13.1% in 2016), 002 (8% compared to 8.5% in 2016, 078-126 (4.3% compared to 1.3% in 2016). Ridinilazole was very potent against all isolates collected in the US with an MIC 90 of 0.25 mcg/ml, including against all the hypervirulent ribotypes as well as those isolates with antibiotic resistances to other antibiotics in the test panel. Conclusion Ridinilazole showed excellent in-vitro activity against C. difficile isolates in the US, independent of ribotype. There has been a striking change in ribotype distribution compared to 2016, accompanied by a reduction in C. difficile resistance to moxifloxacin and imipenem. Disclosures Cheleste M. Thorpe, MD, Actelion: Grant/Research Support|Deinove: Advisor/Consultant|General Mills: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Summit: Advisor/Consultant|Summit: Grant/Research Support Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant Dale N. Gerding, MD, Destiny Pharma plc.: Advisor/Consultant Karen C. Carroll, MD, Abbott Diagnostics: Advisor/Consultant|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|BioRad, Inc: Grant/Research Support|Meridian Biosciences: Grant/Research Support|Roche Diagnostics: Advisor/Consultant|Scanogen, Inc: Advisor/Consultant|Scanogen, Inc: Grant/Research Support|Thermo Fisher, Inc: Advisor/Consultant Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|cidara: Advisor/Consultant|cidara: Grant/Research Support|Paratek: Grant/Research Support|Seres Health: Grant/Research Support|Summit: Grant/Research Support Esther Duperchy, PhD, Summit Plc: Employee David R. Snydman, MD, Merck: Advisor/Consultant|Merck and Company: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres: Advisor/Consultant|Seres Health: Grant/Research Support|Summit Plc: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Visterra: Advisor/Consultant.

Histological features of Clostridioides difficile colitis in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection, although clinically important infections can be difficult to recognise. C. difficile infection does not produce pseudomembranes when it occurs in IBD patients. These individuals may also be colonised by the organism, in which case diarrhoeal symptoms are not necessarily attributed to C. difficile. We performed this study to determine whether any features distinguished C. difficile-associated colitis from an IBD flare. We reviewed the clinical, endoscopic and biopsy findings from 50 patients with established IBD and worsening diarrhoea, including 22 with concurrent positive C. difficile stool toxin polymerase chain reaction (PCR) assays and 28 with negative C. difficile assay results. We found that C. difficile-infected patients had symptoms and endoscopic findings that were indistinguishable from active IBD. Although most biopsy samples from patients with C. difficile infection showed chronic active colitis indistinguishable from IBD, some displayed neutrophilic infiltrates unaccompanied by plasma cell-rich inflammation involving superficial (41%) and crypt (18%) epithelium as well as neutrophilic infiltrates within lamina propria distant from foci of cryptitis (32%). All three of these features were significantly more common among infected than uninfected patients (4, 0 and 4%; P = 0.002, P = 0.03 and P = 0.02, respectively). Although colonic biopsies from IBD patients with C. difficile infection usually lack features that aid distinction from colitic flares, some cases show an acute colitis pattern not seen in IBD alone. When identified in biopsies from symptomatic IBD patients, these changes should alert pathologists to the possibility of this clinically important infection.

65-Year-Old Man With Weight Loss and Dyspnea on Exertion

65-Year-Old Man With Weight Loss and Dyspnea on Exertion

Higher In Vivo Fecal Concentrations of Clostridioides difficile Toxins A and B in Patients With North American Pulsed-Field Gel Electrophoresis Type 1/Ribotype 027 Strain Infection.

Ultrasensitive, quantitative Clostridioides difficile stool toxin measurement demonstrated significantly higher concentrations of toxins A and B in patients infected with the North American pulsed-field gel electrophoresis type 1/ribotype 027 (NAP-1/027) strain compared with other strains, providing in vivo confirmation of the in vitro association between NAP-1/027 and elevated toxin production.

Outcomes in patients with inflammatory bowel disease and acute gastrointestinal symptoms who test indeterminate for Clostridioides difficile.

BackgroundInflammatory bowel disease (IBD) and Clostridioides difficile infection (CDI) can present with similar symptoms. The current preferred method for diagnosing CDI is the nucleic acid amplification test (NAAT) for C. difficile in stool, followed by reflex toxin enzyme immunoassay (EIA) when NAAT is positive. The clinical significance of NAAT(+)/EIA(-) in the IBD population is uncertain.MethodsThis retrospective cohort included IBD patients who presented with acute onset of gastrointestinal symptoms and a C. difficile NAAT(+) test. The primary outcome was C. difficile recurrence within 12 months. Other outcomes examined included hospital admissions within 30 days of CDI, change of IBD maintenance therapy within 90 days of CDI, and complications such as bowel resection or death.ResultsA total of 71 patients were included. Eighty-four percent of the tests were EIA(-) and among the EIA(-) 88% were treated with antibiotics. Outcomes between EIA(+) and EIA(-) were not significantly different in terms of recurrences, admissions, changes to IBD medications or complications. Outcomes were also similar when comparing those who received antibiotic therapy to those who did not.ConclusionsOur cohort did not demonstrate a significant difference in outcomes between EIA(+) and EIA(-) C. difficile patients. Treatment for EIA(-) patients did not improve outcomes. Even though there may be a role for antibiotic therapy in IBD patients who test NAAT(+)/EIA(-) for C. difficile, further studies will be needed to identify that subpopulation.

S2884 Pelvic Inflammatory Disease as an Unusual Cause of Ascites

Introduction: Pelvic inflammatory disease (PID) is an infection of the upper genital tract, including the uterus, fallopian tubes, and/or ovaries. Neisseria gonorrhea, Chlamydia trachomatis, and Mycoplasma genitalium are the most frequently isolated pathogens. Case Description/Methods: A 25-year-old female presented with an 8-day history of lower abdominal pain associated with fevers, chills, vomiting, and non-bloody diarrhea. Patient denied recent travel, changes in her diet, family history of Inflammatory Bowel Disease. Her abdomen was diffusely tender. Routine laboratory testing was unremarkable. CT scan of the abdomen and pelvis (Figure 1) showed focal small bowel mural thickening, concerning for gastroenteritis. COVID PCR, HIV antigen/antibody, blood cultures, Clostridium difficile toxin and stool pathogen PCR panel were all negative. Patient was presumed to have viral gastroenteritis and was discharged home. She was readmitted two days later for worsening nausea and vomiting. Laboratory testing was significant for WBC 12.7 x 109/L, potassium of 2.8 mEq, INR 1.7, CRP 19.24 mg/dL. A repeat CT abdomen and pelvis (Figure 2) showed a re-demonstration of marked wall thickening of the small bowel most consistent with enteritis, and the development of large loculated ascites in the mid abdomen and pelvis with peritoneal thickening and enhancement. Diagnostic paracentesis showed PMNs 990, RBCs 4000, SAAG < 1.1, total protein 3.7 g/dl, glucose 29 mg/dl, and LDH 1609 U/L. Peritoneal cultures grew Neisseria gonorrhea. Patient was discharged home on a two-week course of IV ceftriaxone, metronidazole and doxycycline with improvement in clinical symptoms. Repeat diagnostic imaging showed interval improvement and resolution of ascites. Discussion: Acute symptomatic PID presents with lower abdominal pain associated with fevers, chills, nausea, vomiting, vaginal discharge and/or intermenstrual bleeding. PID may present with RUQ pain in the setting of liver capsular inflammation, also known as perihepatitis i.e. Fitz-Hugh Curtis Syndrome. Perihepatitis occurs in about 10% of woman with acute PID. However, the development of ascites as a presenting complication of PID is very rare. In this case, the ascites fluid studies were not consistent with portal hypertension with a SAAG < 1.1. In addition, PMNs > 250 cells suggested bacterial peritonitis. Furthermore, per the Runyon’s criteria, this pattern resembled secondary bacterial peritonitis with a total protein >1 g/dL, glucose < 50 mg/dL, and LDH > upper limit of normal serum.Figure 1.: CT abdomen and pelvis on presentation showing small bowel mural thickening and enhancement.Figure 2.: CT abdomen and pelvis on representation showing large volume ascites with continued small bowel mural thickening and enhancement.

S3532 Persistent Hiccups: A Rare Case of Acute Colitis Related to COVID-19

Introduction: Most COVID-19 infections present with respiratory symptoms yet gastrointestinal symptoms have been increasingly reported prior to the onset or in complete absence of respiratory symptoms Common symptoms noted include loss of appetite, nausea, vomiting, abdominal pain and diarrhea. There are few cases of COVID-19 related colitis in the current literature. We present a rare case of COVID-19 colitis with the atypical presentation of persistent hiccups. Case Description/Methods: A 57 year old male with a PMHx of HTN, Parkinson’s disease, stroke and localized colorectal adenocarcinoma presents to our institution with persistent hiccups and hypotension. The patient was started on chemotherapy (Capecitabine + Oxaliplatin) 3 weeks prior. In the last 7 days, he had GERD, nausea, anorexia, mild abdominal discomfort and diarrhea. Initial laboratories recorded mild microcytic anemia, and acute kidney injury. He was started on IV hydration. Results were negative for C. difficile toxin, rotavirus, stool fat, stool leukocytes, ova/parasites, and negative growth in cultures. Hypotension resolved after 24 hours. Despite treatment, he continued with hiccups, abdominal pain and PO intolerance. The patient suffered respiratory failure secondary to aspiration due to hiccups; and was placed on MV for 24 hours. At this point, COVID-19 PCR pharyngeal swab returned positive. Abdominopelvic CT scan was performed due to persistent symptoms, demonstrating edematous ascending colon and distal ileum consistent with colitis. Further work-up revealed normal pH and lactic acid levels. He was placed on NPO and IV antibiotics. After 14 days, the patient was discharged. Discussion: Both gastrointestinal (GI) symptoms and hiccups have been reported as atypical presentations of COVID-19 infection previously, but not concomitantly and even separately, rarely. Physicians must be suspicious of GI symptoms, with persistent hiccups, in the pandemic in order to diagnose COVID-19 infection and avoid further GI complications including ischemic, ileus and perforation; or the onset of severe respiratory complications.

S1745 Immune-Mediated Colitis Complicated by Peri-Colonic Abscess and Colonic Perforation Managed by Percutaneous CT-Guided Drainage

Introduction: Immune checkpoint inhibitors have revolutionized the field of oncology, but they are associated with many gastrointestinal adverse effects. Management includes high-dose steroids but may require a second-line immunosuppressant. However, severe cases can be refractory to standard treatment. Case Description/Methods: We present a case of a 73-year-old male with metastatic renal cell carcinoma status post left nephrectomy on nivolumab who presented to an outside institution with painless hematochezia. Colonoscopy demonstrated pan-diverticulosis with ascending and transverse colitis with ulcerations, however biopsies were negative for cytomegalovirus DNA. Extended enteric pathogen stool and Clostridium difficile stool studies were negative. These studies lowered the suspicion of infectious colitis and suggested the diagnosis of immunotherapy-induced colitis. Therefore, he was initiated on steroids. During the hospitalization, patient continued to have copious amounts of diarrhea, which led to hypovolemic shock and vasopressor support. The diarrhea subsequently turned into large volumes of hematochezia and the patient required multiple transfusions for his anemia. He was then transferred to our institution for further workup of immunotherapy-induced colitis refractory to steroid therapy. At our institution, repeat colonoscopy demonstrated severe inflammation in the transverse and descending colon, characterized by deep ulcerations (Fig. 1A and B). Hospital course was complicated by uncontrolled duodenal ulcer hemorrhage despite epinephrine injection, which necessitated embolization of the gastroduodenal artery. Subsequent computed tomography (CT) angiography showed perforated descending colonic diverticulitis and air collection adjacent to the descending colon. Due to his multiple comorbidities, the risks of surgery outweighed the benefits. He underwent CT-guided aspiration and drain placement for the fluid collection. Due to continued bleeding, another colonoscopy was repeated, but was aborted due to presence of medium sized tear (Fig. 1C). The patient continued to decompensate throughout a prolonged hospitalization and later passed away. Discussion: To our knowledge, this is the first case of immune checkpoint inhibitor colitis that led to concomitant colonic perforation and peri-colonic abscess. Our case highlights a rare but potential fatal complication associated with immune check point inhibitors.Figure 1.: ∼7cm pedunculated polyp in the ascending colon.