Difficile Testing Research Articles

High-Resolution Melting PCR as a Fast and Simple Molecular Biology-Based Method for the Identification of Hypervirulent Clostridioides difficile Strains Directly in Stool Samples

Clostridioides difficile became one of the main causes of nosocomial infections in all clinical settings worldwide, especially among patients undergoing antibiotic therapy. The incidence and severity of C. difficile infections, from mild diarrhea to life-threatening pseudomembranous colitis, correlate with the spread of the hypervirulent binary toxin (CDT)-producing strains. The use of the real-time HRM-PCR method enables the identification of hypervirulent C. difficile strains directly in the diarrheal stool samples of patients suspected of being infected with this bacterium. For this purpose, the cdtA and cdtB genes encoding CDT subunits, as well as the species-specific gluD gene, were detected to identify the presence of this bacterium in the tested samples. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the established method were also assessed. The obtained results were compared with the results of eazyplex® C. difficile complete test (AmplexDiagnostics GmbH) based on the LAMP method, used in standard microbiological diagnostics. The values of the assessed diagnostic parameters for the detected genes ranged from 58.82% to 98.85%. The lowest value (58.82%) was obtained for the PPV of cdtB and the highest (98.85%) for the NPV of this gene. The real-time HRM-PCR method enables fast and simple detection of the investigated genes of hypervirulent C. difficile strains and, after careful optimization, may demonstrate high potential for usefulness in routine microbiological diagnostics.

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

To evaluate the impact of changes in the size and characteristics of the hospitalized patient population during the COVID-19 pandemic on the incidence of hospital-associated Clostridioides difficile infection (HA-CDI). Interrupted time-series analysis. A 576-bed academic medical center in Portland, Oregon. We established March 23, 2020 as our pandemic onset and included 24 pre-pandemic and 24 pandemic-era 30-day intervals. We built an autoregressive segmented regression model to evaluate immediate and gradual changes in HA-CDI rate during the pandemic while controlling for changes in known CDI risk factors. We observed 4.5 HA-CDI cases per 10,000 patient-days in the two years prior to the pandemic and 4.7 cases per 10,000 patient-days in the first two years of the pandemic. According to our adjusted segmented regression model, there were neither significant changes in HA-CDI rate at the onset of the pandemic (level-change coefficient = 0.70, P-value = 0.57) nor overtime during the pandemic (slope-change coefficient = 0.003, P-value = 0.97). We observed significant increases in frequency and intensity of antibiotic use, time at risk, comorbidities, and patient age before and after the pandemic onset. Frequency of C. difficile testing did not significantly change during the pandemic (P= 0.72). Despite large increases in several CDI risk factors, we did not observe the expected corresponding changes in HA-CDI rate during the first two years of the COVID-19 pandemic. We hypothesize that infection prevention measures responding to COVID-19 played a role in CDI prevention.

S256 Impact of Patient and Provider Variability on Compliance With C. difficile Testing for IBD Flares

S256 Impact of Patient and Provider Variability on Compliance With C. difficile Testing for IBD Flares

Clostridioides difficile Infections in Children: What Is the Optimal Laboratory Diagnostic Method?

The diagnosis of Clostridioides difficile infection (CDI) in the pediatric population is complicated by the high prevalence of asymptomatic colonization, particularly in infants. Many laboratory diagnostic methods are available, but there continues to be controversy over the optimal laboratory testing approach to diagnose CDI in children. We evaluated commonly used C. difficile diagnostic commercial tests in our pediatric hospital population at Sidra Medicine in Doha, Qatar. Between June and December 2023, 374 consecutive stool samples from pediatric patients aged 0-18 years old were tested using: Techlab C. diff Quik Chek Complete, Cepheid GeneXpert C. difficile, QIAstat-Dx Gastrointestinal Panel, and culture using CHROMagar C. difficile. The results of these tests as standalone methods or in four different testing algorithms were compared to a composite reference method on the basis of turnaround time, ease of use, cost, and performance characteristics including specificity, sensitivity, negative predictive value, and positive predictive value. Our study showed variability in test performance of the different available assays in diagnosing CDI. In our population, a testing algorithm starting with Cepheid GeneXpert C. difficile PCR assay or QIAstat-Dx Gastrointestinal panel as a screening test followed by toxin immunoassay for positive samples using the Techlab C. diff Quik Chek Complete kit showed the best performance (100% specificity and 100% positive predictive value) when combined with clinical review of the patient to assess risk factors for CDI, clinical presentation, and alternative causes of diarrhea.

A case of community-acquired Clostridioides difficile infection causing intussusception, severe pneumonia, and severe hypokalemia

BackgroundClostridioides difficile infection is associated with antibiotic use and manifests as diarrhea; however, emerging cases of fulminant diarrhea caused by binary toxin-producing C. difficile unrelated to prior antibiotic exposure have been reported. Although fulminant colitis caused by C. difficile has been documented, instances of intussusception remain scarce. Here, we present a case of adult intussusception with severe hypokalemia and pneumonia resulting from a community-acquired C. difficile infection in Japan.Case presentationAn 82-year-old male presented with dizziness, progressive weakness, and diarrhea. Initial vital signs indicated severe respiratory and circulatory distress, and laboratory findings revealed hypokalemia, pneumonia, and septic shock. Imaging confirmed intussusception of the ascending colon. Although colonoscopy suggested a potential tumor, no malignancy was found. The C. difficile rapid test result was positive, indicating community-acquired C. difficile infection. Treatment with vancomycin was initiated; however, intussusception relapsed. Surgical intervention was successful and led to clinical improvement.The patient's complex pathophysiology involved community-acquired C. difficile-induced severe diarrhea, hypokalemia, hypermetabolic alkalosis, and subsequent intussusception. Although adult intussusception is uncommon, this case was uniquely linked to binary toxin-producing C. difficile. The identified strain, SUH1, belonged to a novel sequence type (ST1105) and clade 3, suggesting a highly virulent clone. Resistome analysis aligned with phenotypic susceptibility to metronidazole and vancomycin, confirming their treatment efficacy.ConclusionThis case report highlights a binary toxin-producing C. difficile that caused intussusception. The consideration of community-acquired C. difficile in the differential diagnosis of severe enteritis is necessary, even in Japan.

Comparative evaluation of the STANDARD M10 and Xpert C. difficile assays for detection of toxigenic Clostridioides difficile in stool specimens.

This study compared the performance of two commercial molecular assays, the STANDARD M10 Clostridioides difficile assay (M10) and the Xpert C. difficile assay (Xpert), for detecting toxigenic C. difficile in stool specimens. A total of 487 consecutive stool specimens submitted for routine C. difficile testing between June and November 2023 were included. Following routine testing using C. DIFF QUIK CHEK COMPLETE (QCC), M10 and Xpert were tested in parallel, alongside toxigenic culture (reference standard). Additionally, two-step algorithms, using QCC on the first step and either M10 or Xpert on the second step, were assessed. Both M10 and Xpert demonstrated a sensitivity and negative predictive value (NPV) of 100%. M10 exhibited significantly higher specificity and positive predictive value (PPV; 91.9% and 64.2%, respectively) than Xpert (90.3% and 59.8%, respectively). Both two-step algorithms showed a sensitivity and NPV of 98.4% and 99.8%, respectively. The specificity and PPV of the two-step algorithm using M10 (95.2% and 75.0%, respectively) were slightly higher than those of the one using Xpert (94.8% and 73.2%, respectively), without statistical significance. Receiver operating characteristic curve analysis, assessing the predictive ability of cycle threshold (Ct) values for the detection of free toxin, exhibited an area under the curve of 0.825 for M10 and 0.843 for Xpert. This indicates the utility of Ct values as predictors for the detection of free toxin in both assays. In conclusion, M10 proves to be an effective diagnostic tool with performance comparable to Xpert, whether utilized independently or as part of a two-step algorithm.

Leveraging the Electronic Medical Record in C. difficile Diagnostic Stewardship

Background: Clostridioides difficile PCR is extremely sensitive but cannot differentiate colonization versus active disease. Over diagnosis of C. difficile infection (CDI) has negative consequences including overuse of antibiotics targeting C. difficile, increased hospital-acquired (HA)-CDI rates, and increased healthcare costs. We describe the implementation of a Clinical Decision Support tool embedded in the C. difficile order and the result on testing, HA-CDI rates and healthcare costs. Methods: The C. difficile order was updated in June 2023 with 4 dynamic questions that reflex if specific criteria are identified in the electronic medical record in the prior 24 hours: less than 3 loose stools documented, receipt of laxative, opioid antagonist, oral contrast, or tube feed initiation. If any criteria are identified, an embedded alert triggers and the provider must choose “yes, high clinical suspicion” or “no (exit and cancel order)” in addition to providing an order indication. All inpatient C. difficile tests were reviewed from July 1 to Sept 30, 2022 (pre-update) and July 1 to Sept 30, 2023 (post-update). An order rate was calculated per 10,000 patient days as well as HA-CDI rate. Cost analysis was completed using direct lab costs and published costs of $35,000 per HA-CDI. Results of the order questions were reviewed post-update. Incident rate comparison was completed using medcalc. Results: Pre-update, 1147 tests were conducted, with an order rate of 104.3. Post-update, 919 tests were performed, with an order rate of 86.6. The positivity rate was 16.1% pre-update and 14.7% post-update. The incidence rate difference was 0.00177 (P 15 (145, 16%). 166 (18%) patients who received laxatives (18 positive, positivity rate 11%) were still tested. Conclusion: Implementation of a dynamic order led to a significant reduction in the total number of C. difficile PCR tests performed with associated reduction in HA-CDI and cost savings. Despite this, patients receiving laxatives were still being tested for C. difficile, highlighting the need for ongoing education and feedback. These results support the use of dynamic ordering for diagnostic stewardship, which can benefit both patients and hospitals.

Impact of Clostridioides difficile Reporting on Antimicrobial Therapy Days Directed at Treatment of C. difficile Infections

Background: Previous studies have found that solely relying on molecular testing is likely to result in the overdiagnosis and overtreatment of C. difficile infections (CDI). Comparable outcomes have been demonstrated in patients with a positive molecular test (C. difficile PCR) result and a negative toxin immunoassay (C. difficile toxin) compared to patients without CDI by either testing Method: In 2021 Memorial Hermann Healthcare System converted from C. difficile PCR testing only to C. difficile PCR testing with reflex to C. difficile toxin if positive. A previous internal audit revealed that despite this change in testing, patients who were C. difficile PCR positive and C. difficile toxin negative were still receiving treatment. This study aimed to evaluate the impact of C. difficile reporting on the total days of therapy directed at the treatment of CDI of an 11-hospital health care system in patients who testing C. difficile PCR positive/C. difficile toxin negative. Methods: Pre-post, multicenter, retrospective, observational study conducted from January 1, 2023 through March 31, 2023 (pre-intervention) and July 1, 2023 through September 31, 2023 (post-intervention) which included hospitalized adult patients with a C. difficile test ordered within the study period. Intervention included a change in reporting of C. difficile PCR positive/C. difficile toxin negative results to display a laboratory comment. The comment notifies providers of the positive C. difficile PCR result while highlighting this probably reflects colonization with C. difficile as the C. difficile toxin is negative and treatment is rarely indicated. Results: In total, 989 C. difficile PCR were order in the pre-intervention cohort compared to 1009 in post-intervention. The overall rate of patients that received therapy directed at CDI decreased from 14% to 10% after the implementation of reporting change. Total days of therapy (DOT) also decreased by 29% from 482 to 342. Days of therapy that were administered to patients with C. difficile PCR positive/negative C. difficile toxin test decreased from 183 to 91. Conclusions: Adjusting the reporting of C. difficile results led to an overall numerical decrease of antimicrobial DOT directed at CDI treatment. In particular, among patients with a positive C. difficile PCR/C. difficile toxin negative test a 50% reduction in DOT was observed. Further data are required to assess the overall clinical impact of adjusting CDI reporting methods.

Audit and Feedback to Ordering Providers to Reduce Inappropriate C. difficile Testing and Hospital Onset C. difficile Rate

Background: Inappropriate Clostridioides difficile (C. difficile) laboratory testing is common in hospitals and leads to over diagnosis, unnecessary treatment, and elevated hospital onset C. difficile infection (HO-CDI) metrics. Diagnostic stewardship is essential to avoid inappropriate testing, but limited data exists on optional interventions. Methods: A diagnostic stewardship intervention targeting CDI testing comprised of education and prospective audit with feedback was performed a VA facility (inpatient, outpatient, and long-term care units). Education on appropriate indications for CDI testing was provided in pre-intervention (9/2022 to 5/2023) and intervention periods (6/2023 to 12/2023). During the intervention period, all CDI tests (positive or negative) were audited after completion in real-time by an Infectious Diseases physician and feedback was given to ordering providers and/or their supervising physician (if trainee) for all tests not meeting an appropriate indication. Appropriate indication was defined as ≥3 liquid stools in 24 hours or symptoms of fulminant disease. Testing was considered inappropriate if no clinical symptoms, patient received laxatives within 48 hours, test was performed for test-of-cure or within 7 days of a prior test with no clinical change, or delayed testing in patients with diarrhea on admission. The rate of HO-CDI per 10,000 bed days of care (BDOC) per LabID event was compared during the pre-intervention and intervention periods, and ordering appropriateness was compared for all tests and hospital onset tests before (3/2023-5/2023) and after (6/2023-12/2023) feedback was performed. Results: After starting audit and feedback, HO-CDI rate decreased from 3.92 per 10,000 BDOC to 0.99 per 10,000 BDOC (p=0.03). HO-CDI rate among tests that were inappropriate was 2.19 and 0.80 per 10,000 BDOC during the pre-intervention and intervention periods, respectively (p=0.40). Average overall tests per month decreased from 37.8 to 28.1 after the intervention. Rate of all inappropriate tests decreased from 16.25 to 7.96 per 10,000 BDOC (p=0.04) and rate of hospital onset inappropriate tests trended toward decrease from 9.29 to 4.77 tests per 10,000 BDOC (p=0.07). The most common reasons for inappropriate testing were < 3 episodes of diarrhea in 24 hours (54% pre-intervention, 65% intervention) and laxative use (57% pre-intervention, 45% intervention). No cases of delayed testing leading to worsened disease were identified during the intervention. Cost savings for decreased tests were estimated at $150-300 per month. Conclusion: An intervention comprised of education and real-time audit and feedback of all CDI tests obtained at a VA facility resulted in decreased inappropriate testing and reduced the rate of HO-CDI.

Patient First Strategies for Reducing Inequities in HAI Prevention

Background: Inequities in healthcare-associated infections (HAI) incidence and prevention measures are critically important to understand (Chen,2021). While evaluations are beginning to characterize these disparities by infection type (Gettler, 2023), our work expands this by characterizing disparities by prevention strategies. By better understanding how evidence-based prevention strategies are implemented at the patient level, infection preventionists and hospital epidemiologists can better design strategies that provide equitable care to all patients. Methods: Beginning January 2023, gender, race, ethnicity, spoken language, and age group fields were added to daily chlorhexidine gluconate (CHG) treatment and C. difficile test order compliance data captured via electronic medical record. In July 2023, fields on recorded race, ethnicity, and gender were added to well-established foley and vascular access real-time peer audit tools that are used by infection preventionists (IPs). Each prevention strategy variable was summarized by demographic variables and differences in compliance were measured using chi-square tests. Results: 899 vascular audits and 420 foley audits were completed by IPs between July – December 2023. In 2023, there were 114,066 opportunities for CHG Treatment and 1,991 C. difficile test orders. Missing data varied by metric but ranged from 0-60%. Statistically significant differences by race were found in 3 of 8 components (i.e., intact seal, secured catheter and absence of dependent loop) in the foley audit (p < 0 .01) and compliance with C. difficile test ordering (p < 0 .01). No differences in race were found in vascular access audits or CHG treatment. No differences in gender or ethnicity were noted in foley, vascular access audits, CHG treatment compliance, or C. difficile testing. Differences in gender and age were found in CHG treatment compliance (p < 0 .001). Conclusions: By focusing more on patient level process measures rather than only presenting stratified outcomes data, we can identify targeted opportunities for improvement in health equity before our patients develop an HAI. Further evaluations should also focus on assessing the clinical relevance of statistical findings to better inform intervention strategies. Separately, efforts are needed to improve completeness and integrity of demographic data in the electronic medical record.

Automated Discontinuation of Isolation Precautions with the Use of Electronic Health Record Tools

Background: At a comprehensive cancer center, hundreds of patients are screened daily for infections requiring the implementation of isolation precautions. Discontinuation of precautions is determined by negative testing, resolution of infection, or other criteria. Determining appropriate discontinuation of isolation precautions is labor intensive for Infection Preventionists (IPs). An unintended consequence of manual discontinuation is that numerous patients remain on isolation indefinitely. This was amplified during the COVID-19 pandemic when thousands of patients were placed on isolation precautions. Using electronic health record (EHR) tools, opportunities for process improvements were developed. Our goal was to establish an automated method to resolve isolation precautions. We aimed to decrease the number of manually resolved precautions by 25% each fiscal year (FY), compared to our baseline of activity in FY 2019 (FY19). Our secondary aim was to automate adding and resolving precautions when testing is initiated for suspected transmissible conditions (rule-out testing features).Methods: Infection Control (IC) collaborated with EHR analysts to build tools to automate a process for appropriate isolation discontinuation. We reviewed our internal data in conjunction with evidence-based guidelines and started with acute, short-term infections that do not require repeat testing or cultures. Expiration dates were established for these infections to resolve automatically after meeting criteria. A secondary review determined that additional infections could be added safely to this process. The secondary aim of establishing rule-out testing was implemented for respiratory viral panels (including SARS-COV-2) and C. difficile testing. When testing was ordered for these conditions, a suspect-infection status and alert for precautions were automatically added to patients’ EHR banners. If the assay resulted negative, the suspect-infection status was automatically removed from their chart. Results: Our baseline of active infections in FY19 was approximately 2,700 cases. From FY19 through FY23, 123,115 infections were added to our patients, and 128,422 infections were resolved. In the first year of implementation, there was a 58% decrease in the number of manually resolved cases. From the initiation of our project through the end of FY23, manual discontinuation of precautions has decreased by 88%. Conclusions: We successfully implemented a process improvement project to appropriately remove patients from isolation precautions automatically using EHR tools, which resulted in reduced labor on our IPs and patient time spent on isolation restrictions. Additional benefits from this process improvement extend to decreasing unnecessary costs to the patient and the organization, better stewardship of supply/resources, and improving patient satisfaction.

Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection

Background and aimsClostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. MethodsThis multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) eight weeks after the last FMT treatment. Secondary outcomes included CDAD cure one and eight weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. ResultsWe included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range (IQR) 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%, 95% confidence interval (CI) 71-79%) at week one. At week eight, 255 patients (55%, 95% CI 50-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%, 95% CI 75-82%). The 90-day mortality was 10% (95% CI 8-14%). ConclusionRepeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival.

ITS 97 - Implementing an electronic best practice advisory to reinforce Clostridioides difficile testing

ITS 97 - Implementing an electronic best practice advisory to reinforce Clostridioides difficile testing

Characteristics of Patients With Initial Clostridioides difficile Infection (CDI) That Are Associated With Increased Risk of Multiple CDI Recurrences.

Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI. Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.

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.

P298 Adherence to diagnostic and treatment recommendations for the management of acute severe ulcerative colitis: a prospective and multinational study

Abstract Background Acute severe ulcerative colitis (ASUC) is a serious, potentially life-threatening condition. Hospital admission and prompt medical therapy with intravenous steroids is crucial, but rescue medical therapy is frequently needed, and surgery is often required. Our aim was to assess the adherence to main diagnostic and management recommendations within the MASC multinational study. Methods MASC was a prospective, multinational cohort study, including all consecutive patients hospitalized for ASUC between February 2019-January 2020. The primary outcome was surgery during the first 90 days after admission. We used descriptive statistics to determine the proportion of patients fulfilling each diagnostic and treatment recommendation according to ECCO and AGA. Results A total of 823 patients from 123 centers in 32 countries in five continents were included (median age 39 years [IQR, 28-54], 56% male, 64% non-smokers; Table 1). Most cases (74%) had a previous diagnosis of ulcerative colitis, and around half (48%) with prior ASUC episodes. Upon admission, they were under 5-ASA therapy (60%), thiopurines (14%), or biologics (21%). They were mostly admitted to the Gastroenterology ward (74%). During the initial assessment, 112 patients (15%) did not have stool culture or C. difficile testing, and CMV was evaluated in 50% of cases. Endoscopic assessment was performed in 66% of patients, mainly by flexible rectosigmoidoscopy (74%). Regarding treatment, 3.4% of patients received exclusive parenteral nutrition, 70% low molecular weight heparin, and 42% prophylactic antibiotics (Table 2). Steroids were started after a median of 0 days (IQR, 0-1), mostly with methylprednisolone or hydrocortisone (64%), 26% with other steroids, and 7% were managed without steroids. Infliximab was started in 159 patients (19%) after a median of 6 days (IQR, 4-8) after starting steroids, with 27% after &amp;gt;7 days. Most of the patients (93%) had some type of tuberculosis screening done prior to infliximab. Twenty-eight patients (3.4%) started cyclosporine. Thirty-two patients (4%) received other rescue therapy different from infliximab or cyclosporin. Colectomy was performed in 25 patients (3%). Conclusion The diagnostic and medical management of ASUC remains heterogeneous and different from current recommendations. This context demands more evidence and consensus on the best management of ASUC.

Comparison of Clostridioides difficile nucleic acid amplification test (NAAT) results using fresh and frozen stool specimens and rectal swabs.

Nucleic acid amplification tests (NAATs) are frequently used in Clostridioides difficile research and diagnostic testing, but the effect of freezing specimens on C. difficile NAAT performance is not well characterized. This study evaluated the concordance of NAAT results between fresh and frozen specimens (fecal and rectal swabs) and found it to be very good to excellent. The results indicate that frozen fecal and rectal swab specimens may be used for C. difficile NAAT testing in research when fresh specimens are not available.

The Overuse of C. Difficile Testing Among Autologous Transplant Patients with Melphalan Conditioning: A Single Center Experience

Introduction: Melphalan is a common chemotherapy agent used as conditioning prior to autologous stem cell transplants (Auto SCT). Most frequent side effects are gastrointestinal (GI), with 91% of trial participants reporting symptoms. Among these complaints, diarrhea is the most common with a median onset of symptoms at 7 days and complaints lasting upwards of 17 days. Despite these known post-chemotherapy GI complications, transplant patients are often tested for Clostridium difficile ( C. difficile) given their immunocompromised status. Our study evaluated the rate of C. difficile testing in post-transplant patients to explore its utility and possible overuse in this population. Methods: During 2017-2022, patients who underwent Melphalan conditioning prior to Auto SCT were reviewed for C. difficile testing during transplant admission. We analyzed the timing and the results of C. difficile tests obtained during admission. All C. difficile tests obtained prior to admission or following discharge were excluded. From 2017-2020, a positive C. difficile test at our institution required only a positive C. difficile PCR test. Criteria for a positive C. difficile test changed beginning 2021, requiring both a positive C. difficle PCR and toxin antigen tests. Results: Of the 202 patients included in our database, 153 were tested for C. difficile during their transplant admission. 12/153 tests were positive (7.8%) with the average day of testing being 5.5 days post-transplant. Twelve patients were tested a second time during the same admission with the second test occurring on an average on day 12 post-transplant. All repeat tests were negative for C. difficile. All C. difficile tests following the implementation of the toxin assay resulted negative. Prior to the toxin assay, all positive PCR tests were treated with oral vancomycin. Conclusion: Our institutional data indicates that excessive C. difficile testing may occur in the setting of Melphalan conditioning. C. difficile testing was noted to be of low yield with positive rates in only 7.8% of patients. Furthermore, the positivity rate dropped to 0% among our cohort after implementation of the toxin assay in 2021. The mean cost of a single C. difficile test at our institution over 2017-2022 was $29.00 and this excessive testing leads to unnecessary financial burden incurred during the admission. Diarrhea occurring post-auto SCT in this population may be better explained as a side effect of Melphalan conditioning. Our data suggest it may be reasonable to withhold or delay testing until at or after day 7 post-transplant. In addition, repeat C. difficile testing within the same admission may be futile with all cases in our cohort resulting negative, further supporting our conclusion that excessive testing occurs in this population. We will further study our data as part of a targeted quality-improvement initiative to assess post-transplant outcomes with immediate versus deferred C. difficile testing.

672. Impact of Multistep Testing Algorithm on Hospital Acquired Clostridioides difficile Infection Rates

Abstract Background Clostridioides difficile infection (CDI) is one of the leading causes of hospital-acquired (HA) infections. Clinically distinguishing true CDI versus colonization is challenging. Our center previously used a polymerase chain reaction (PCR) assay as a standalone test for diagnosing CDI. While PCR is very sensitive for diagnosing CDI, it cannot distinguish between CDI and asymptomatic colonization. A multistep testing algorithm, which consists of an initial C. difficile PCR test followed by a reflex enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) and Toxin A/B testing, was implemented in our institution. We conducted this study to determine the rates of HA-CDI and C. difficile colonization based on laboratory results. Methods This retrospective observational study was conducted at Allegheny General Hospital (Pittsburgh, PA, US). Patients with a positive C. difficile PCR assay at day 3 or later from admission date were included for analysis. The pre-intervention period was from August 2021 to February 2022 and post-intervention period was from August 2022 to February 2023. Before the intervention, results for C. difficile testing were reported as PCR positive (PCR+) or negative (PCR-). On July 2022, a multistep testing algorithm was implemented with an initial C. difficile PCR assay; if results were positive, a reflex EIA for GDH and Toxin A/B testing was performed and resulted as follows: Figure 1. The HA-CDI rates before and after implementation of a multistep testing algorithm were compared. Results A total of 112 unique patients were included. HA-CDI in the post intervention period decreased by 53% after the intervention (N=57 [pre-intervention] versus N=26 [post-intervention]; P &amp;lt; 0.001). During the post-intervention period, there were 55 PCR+ C. difficile assays, of which 29 (53%) were resulted as "indeterminate, likely C. difficile colonization." Of the 29 indeterminate results, 23 (79%) still received CDI therapy. Conclusion Our study demonstrated that a multistep C. difficile testing algorithm significantly reduced the rates of HA-CDI in our institution. We found that the majority of patients still received CDI therapy despite having a negative EIA toxin result. We plan to analyze the clinical impact of this multistep testing algorithm in a follow-up study. Disclosures Thomas L. Walsh, MD, Accelerate Diagnostics: Advisor/Consultant

129. Evaluation of Two-Step Clostridioides difficile Testing on Treatment Exposure

Abstract Background Clostridioides difficile can colonize or cause symptomatic disease from mild diarrhea to severe colonic inflammation requiring surgical intervention. Multiple C. difficile diagnostics are available and national guidelines recommend standalone or combination testing methods. Testing has mostly shifted to polymerase chain reaction (PCR)-based, which has shown up to a 50% increase in reporting of C. difficile infection (CDI). A two-step testing method has also been used to discern colonization versus active infection. The National Healthcare Safety Network has proposed changes to CDI reporting to include results and treatment, emphasizing the importance of diagnostic and antimicrobial stewardship. Methods In 2021 Saint Luke’s Health System moved from C. difficile PCR standalone to two-step testing with PCR and enzyme immunoassay (EIA) toxin test. If PCR is positive, an EIA is run. Both results are reported including interpretation guidance. A retrospective cohort study was conducted to evaluate if two-step testing impacts antibiotic prescribing rates for C. difficile. The pre-implementation group included PCR-only and post- implementation was split into PCR +/ EIA - and PCR +/ EIA + groups. Results Treatment rates for C. difficile did not significantly change after implementation of two-step testing (100% pre- vs 92% PCR +/ EIA - and 97% PCR +/ EIA +, p = 0.093). For PCR +/ EIA - results, treatment initiation more often occurred prior to results being available compared to the post-implementation PCR +/ EIA + group and pre-implementation group (30.3% PCR +/ EIA - vs 19.6% PCR +/ EIA + and 7.8% pre-implementation, (p = 0.028)). C. difficile antibiotic prescribing rates at discharge were no different between groups as the highest rates of treatment continuation were seen in the PCR +/ EIA - group (79.4% PCR +/ EIA - 72.5% pre-implementation vs 71.7% PCR+/ EIA +, p = 0.706). Conclusion Despite PCR +/ EIA - results, clinicians tended to treat patients irrespective of PCR-only or two-step results. The impact of two-step C. difficile testing on treatment rates was limited and prescribing rates did not significantly change. The findings of this study warrant investigation into alternative solutions to promote aligned diagnostic and antimicrobial stewardship. Disclosures All Authors: No reported disclosures