Initial Clostridioides Difficile Infection Research Articles

205. Utilization of the Four Themes of the CDC/ATSDR SVI Interactive Map in Assessing Initial Clostridioides difficile Infection Outcomes

Abstract Background Social determinants of health (SDoH) (e.g., education, clean water, health care access) are external factors shown to impact health outcomes. Inequities in SDoH have been hypothesized to contribute to poorer Clostridioides difficile infection (CDI) outcomes. The Centers for Disease Control’s (CDC) Social Vulnerability Index (SVI) is a composite measure of neighborhood (census tract) based on four major themes: socioeconomic status (SES), housing characteristics (H&C), race/ethnicity (REM) status, and housing and transportation (H&T). There is a cessation of literature that describes the impact of each SVI theme on CDI outcomes. The objective of this study was to utilize the four themes of the CDC SVI to determine the impact of SDoH on initial CDI severity and all-cause mortality outcomes. Methods Adult patients admitted to Loma Linda University Medical Center (LLUMC) with an initial episode of CDI between January 2020 to June 2021 were included. Patient residential addresses were collected and input into the CDC/ATSDR SVI Interactive Map. Vulnerability groups were congregated into 2 main subgroups [patients with SVI scores of < 0.4999 are grouped as low vulnerability (LV) and patients with SVI scores of ≥ 0.5 are grouped as high vulnerability (HV)]. Results 206 patients were included, and those with an overall HV SVI score were more likely to have a higher all-cause mortality rate and to present with severe or fulminant initial CDI compared to those with a LV score. The frequency of initial severe CDI was 3x greater for the SVI themes of SES and H&C [61/206 (29.61%) vs 19/206 (9.22%)] in patients with a HV score compared to those with LV scoring. Further, patients who presented with an HV score for the H&T theme were more likely to present with initial severe (26.21% vs 12.62%) or fulminant CDI (13.11% vs 5.34%) versus those with a LV score. When considering the REM status theme, the initial fulminant CDI diagnosis was about 37x greater among individuals with a HV score (17.96% vs 0.49%) and mortality 9x greater when compared to those with LV scoring (8.74% vs 0.97%). Conclusion HV scores across SES, H&C, REM status, and H&T correlate with increased CDI severity and mortality rates. Further research and targeted interventions should be identified. Disclosures Anna Zhou, PharmD, Melinta Therapeutics: Honoraria Jacinda C. Abdul-Mutakabbir, PharmD, MPH, CSL Sequiris: Advisor/Consultant|CSL Sequiris: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria

Comparing rates of recurrent infection for first occurrence of Clostridioides difficile between tapered oral vancomycin and standard vancomycin: a retrospective, propensity matched cohort study.

To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin. Retrospective cohort study. Community health system. Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10-14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen. Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI. The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07-0.56, p < 0.002). Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.

A Retrospective Assessment of Guideline Adherence and Treatment Outcomes From Clostridioides difficile Infection Following the IDSA 2021 Clinical Guideline Update: Clostridioides difficile Infection

Abstract Background The 2021 update to the Infectious Diseases Society of America Clostridioides difficile infection (CDI) guidelines recommended fidaxomicin as the preferred treatment over vancomycin for patients with initial and recurrent CDI. Few studies have examined how treatment patterns and clinical outcomes of hospitalized CDI patients changed after the postguideline update or contemporary real-world outcomes of fidaxomicin vs vancomycin. Methods This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections. Results A total of 45 049 patients with CDI from 779 US hospitals met initial inclusion criteria. Comparing the pre vs post periods, the proportion of patients treated with fidaxomicin increased from 5.9% to 13.7% (P &amp;lt; .001), vancomycin use decreased from 87.9% to 82.9% (P &amp;lt; .001), and metronidazole use decreased from 21.6% to 17.2% (P &amp;lt; .001). When comparing fidaxomicin vs vancomycin in the post period, fidaxomicin was associated with lower CDI recurrence (6.1% vs 10.2%; P &amp;lt; .001) and higher sustained clinical response (91.7% vs 87.8%; P &amp;lt; .001). Ninety-day postdischarge costs were not significantly different between groups. A sensitivity analyses showed similar findings. Conclusions Since the 2021 guideline update, fidaxomicin use has increased significantly but could be further utilized given its association with better clinical outcomes and no increase in postdischarge costs.

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

Systematic review of the orally administered microbiome therapeutic, fecal microbiota spores, live-brpk, to prevent recurrence of Clostridioides difficile infection in adults.

Clostridioides difficile infection (CDI) has been linked to over 200,000 cases of illness in hospitalized patients and over 20,000 deaths annually. Up to 25% of patients with an initial CDI episode will experience recurrent CDI (rCDI), which most commonly occurs in the first 8 weeks following antibiotic therapy. In patients with first or multiple rCDI, infection, the microbiome is similarly disrupted, which highlights the challenges of using antibiotics alone while underscoring the need for microbiome restoration regardless of the number of recurrences. In this systematic review, we describe the role of the gastrointestinal microbiome in CDI, and systematically review fecal microbiota spores, live-brpk (VOWST™; VOS for Vowst Oral Spores) for prevention of recurrence in rCDI. The PubMed database was searched using "recurrent Clostridioides difficile infection" AND (SER-109 OR VOS) and limited to clinical trials. The search yielded 7 results: 3 articles describing 3 clinical trials (two Phase 3 trials (ECOSPOR III and ECOSPOR IV) and one Phase 2 trial (ECOSPOR)), 1 describing follow-up of ECOSPOR III, 1 describing a post hoc analysis of comorbidities in ECOSPOR III, and 2 describing health-related quality of life in ECOSPOR III. Compared with placebo, VOS following standard-of-care antibiotics for CDI significantly reduced risk of recurrence at 8 weeks (relative risk, 0.32 (95% CI: 0.18-0.58); p < 0.001; number needed to treat: 4) with a tolerable safety profile; rCDI rates remained low through 24 weeks. The disrupted microbiome, secondary to/exacerbated by antibiotic treatment, was rapidly (i.e., Week 1) restored with VOS. Compared with placebo, VOS demonstrated greater improvements in health-related quality of life. Clinical care of patients with rCDI now includes Food and Drug Administration-approved therapeutics to address microbiome restoration. Clinical trial evidence supports use of VOS following antibiotics and importance of microbiome restoration in rCDI.

Microbiome profile and calprotectin levels as markers of risk of recurrent Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is the main cause of nosocomial diarrhoea in developed countries. Recurrent CDI (R-CDI), which affects 20%-30% of patients and significantly increases hospital stay and associated costs, is a key challenge. The main objective of this study was to explore the role of the microbiome and calprotectin levels as predictive biomarkers of R-CDI. We prospectively (2019-2021) included patients with a primary episode of CDI. Clinical data and faecal samples were collected. The microbiome was analysed by sequencing the hypervariable V4 region of the 16S rRNA gene on an Illumina Miseq platform. We enrolled 200 patients with primary CDI, of whom 54 developed R-CDI and 146 did not. We analysed 200 primary samples and found that Fusobacterium increased in abundance, while Collinsella, Senegalimassilia, Prevotella and Ruminococcus decreased in patients with recurrent versus non-recurrent disease. Elevated calprotectin levels correlated significantly with R-CDI (p=0.01). We built a risk index for R-CDI, including as prognostic factors age, sex, immunosuppression, toxin B amplification cycle, creatinine levels and faecal calprotectin levels (overall accuracy of 79%). Calprotectin levels and abundance of microbial genera such as Fusobacterium and Prevotella in primary episodes could be useful as early markers of R-CDI. We propose a readily available model for prediction of R-CDI that can be applied at the initial CDI episode. The use of this tool could help to better tailor treatments according to the risk of R-CDI.

The management of Clostridioides difficile infection: from empirism to evidence.

Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI. In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX. There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.

Investigating the Correlation Between Clostridioides difficile Infection and Vitamin D Deficiency.

Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the US. Symptoms include watery diarrhea, nausea, and anorexia and it can present with leukocytosis on laboratory evaluation. Treatment is based on disease severity and recurrence. Despite antibioticusage being the highest risk factor for infection, they are also the first-line treatment for initial CDI. Prevention of CDI mostly involves good hand hygiene, antibiotic stewardship, and appropriate precautions when interacting with infected individuals. Vitamin D deficiency (VDD) has been linked to CDI, however, there is limited insight into the correlation between both states. Our aim was to further investigate the potential link between VDD and CDI. Data were obtained from the National Inpatient Sample (NIS) from 2016 to 2019. Patients with CDI were identified and stratified based on a diagnosis of VDD. Primary outcomes were mortality, CDI recurrence, ileus, toxic megacolon, perforation, and colectomy. Chi-squared and independent t-tests were performed to assess categorical and continuous data, respectively. Multiple logistic regression was used to control for confounders. Patients with VDD had higher rates of CDI recurrence (17.4% versus 14.7%,p<0.05), but lower rates of mortality (3.1% versus 6.1%, p<0.05). Differences in rates of ileus, toxic megacolon, perforation, and colectomy were statistically insignificant. Length of stay was higher in the VDD group (10.38 days versus 9.83 days). Total charges were lower in the VDD group ($93,935.85 versus $102,527.9). CDI patients with comorbid VDD are at higher risk for the recurrence of CDI. This is likely due to the role of vitamin D in the expression of intestinal epithelial antimicrobial peptides, macrophage activation, and maintenance of tight junctions between gut epithelial cells. Furthermore, vitamin D plays a role in maintaining a healthy gut microbiome. Alternatively, deficiency results in poor gut health and detrimental changes to the gut microbiome. In effect, VDD promotes the proliferation of C. difficile within the large colon, resulting in an increased predisposition for CDI.

Characteristics of Hospitalized Adults 55 and Older With Clostridioides difficile Infection.

Clostridioides difficile infection in older adults can result in severe infection, difficulty in treating, and complicated disease process, yet few studies have examined the characteristics of hospitalized older adults and recurrent Clostridioides difficile infection. A retrospective cohort study was conducted to explore the characteristics of hospitalized adults 55 years and older with initial Clostridioides difficile infection and recurrences by extracting routinely documented data in the electronic health record. A sample of 1,199 admissions on 871 patients was included, with a recurrence rate of 23.9% (n = 208). During the first admission, there were 79 deaths (9.1%). Clostridioides difficile infection recurrence was more prevalent in patients between 55 and 64 years old, and if discharged to a skilled nursing facility or with home health services. Chronic diseases significantly more prevalent in recurrent Clostridioides difficile infection included hypertension, heart failure, and chronic kidney disease. On initial admission, no laboratory abnormalities were significantly associated with recurrent Clostridioides difficile infection. This study indicates the need for utilizing routinely captured electronic health record data during acute hospitalizations to aid in targeting care to reduce morbidity, mortality, and recurrence.

392. Guideline adaptation of fidaxomicin as first-line therapy for Clostridioides difficile infection in institutions across the United States

Abstract Background In 2021, Clostridioides difficile infection (CDI) treatment guidelines were updated to recommend fidaxomicin over oral vancomycin as first-line therapy in initial and recurrent CDI episodes. Prior to this update, fidaxomicin use in management of CDI was limited, as cheaper alternatives were recommended as first-line therapy. The purpose of this study was to assess the guideline adaptation of fidaxomicin as first-line therapy in CDI management in institutions across the United States (US) and to identify barriers to its use. Methods An electronic survey was distributed to members of the American Society of Health-System Pharmacists in April 2022. Baseline demographics, current practices, and barriers to fidaxomicin use were collected. Results were analyzed using descriptive statistics. Fisher’s Exact Test was used to compare categorical variables. Results Based on 63 responses, majority of institutions (41/63, 65%) did not recommend use of fidaxomicin as first-line therapy for CDI. While most hospitals reported having institution specific CDI guidelines (48/63, 76%), over half of institutions with CDI guidelines still recommended oral vancomycin as first-line therapy (26/48, 54%). None of the institutions without CDI guidelines (0/15, 0%) recommended use of fidaxomicin as first-line therapy and majority of them (12/15, 80%) did not have fidaxomicin on formulary or restricted its use to ID services. Recommendation of fidaxomicin as first-line therapy was significantly higher in institutions with CDI guidelines versus those without (46% vs 0%, Fisher’s Exact 0.0006, p&amp;lt; 0.05). Approximately 92% (58/63) of respondents reported at least 1 barrier to using fidaxomicin, with 39.6% (25/63) reporting 2 or more barriers to use. Barriers identified were cost (55/63, 87.3%), lack of formulary inclusion (14/63, 22.2%), lack of provider familiarity (13/63, 20.6%) and inability of patients to afford upon discharge (7/63, 11.1%). Conclusion Majority of institutions do not currently recommend use of fidaxomicin as first-line therapy for CDI despite the recent guideline updates. Institutions with CDI treatment guidelines were more likely to recommend use fidaxomicin as first-line therapy. Cost and lack of formulary inclusion were cited as the most frequent barriers to fidaxomicin use. Disclosures All Authors: No reported disclosures.

Impact of Updated Clinical Practice Guidelines on Outpatient Treatment for Clostridioides difficile Infection and Associated Clinical Outcomes.

BackgroundThe 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) Clostridium (Clostridioides) difficile infection (CDI) guideline update recommended treatment with fidaxomicin or vancomycin for CDI. We aimed to examine outpatient CDI treatment utilization before and after the guideline update and compare clinical outcomes associated with fidaxomicin versus vancomycin use.MethodsA pre-post study design was employed using Medicare data. CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) were compared between patients indexed from April–September 2017 (preguideline period) and those indexed from April–September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin versus vancomycin were compared using propensity score–matched analyses.ResultsFrom the pre- to postguideline period, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) and fidaxomicin (initial CDI: 0.87% to 1.63%; recurrent CDI: 2.2% to 6.0%) use increased significantly (P < .001 for all). However, clinical outcomes did not improve. In propensity score–matched analyses, fidaxomicin versus vancomycin users had 4-week sustained response rates that were higher by 13.5% (95% confidence interval [CI], 4.0%–22.9%; P = .0058) and 30.0% (95% CI, 16.8%–44.3%; P = .0002) in initial and recurrent CDI cohorts, respectively. Recurrence rates were numerically lower for fidaxomicin in both cohorts.ConclusionsVancomycin use increased and metronidazole use decreased after the 2017 guideline update. Fidaxomicin use increased but remained low. Improved outcomes associated with fidaxomicin relative to vancomycin suggest benefits from its greater use in Medicare patients.

Comparison of the Risk of Recurrent Clostridioides Difficile Infections Among Patients in 2018 Versus 2013.

Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had ≥1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P < .0001).

Risk Factors, Diagnosis, and Management of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease

Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.

Cost-effectiveness of Fecal Microbiota Transplantation for First Recurrent Clostridioides difficile Infection.

Both the American College of Gastroenterology and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI. We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial nonsevere CDI, vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27 135/QALY. In probabilistic sensitivity analysis at a $100 000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty. FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.

A12 STEPWISE COORDINATION OF COLONIC NEUTROPHILS AND INNATE LYMPHOID CELLS IN THE ONSET AND RESOLUTION OF CLOSTRIDIOIDES DIFFICILE TOXIN-INDUCED INJURY

BackgroundWhile our understanding and use of treatments for Clostridioides difficile infection (CDI) has improved, initial CDI still carries significant morbidity and mortality owing to heterogeneity in host immune responses. Further, host immunity is a critical modulator of fecal microbiota transplantation (FMT) success in CDI. Thus, understanding the host immune response during CDI is essential.AimsTo assess the cellular immune responses that trigger the onset and resolution of injury and inflammation in CDI.MethodsColonic injury and inflammation triggered by CDI was modelled in mice using intrarectal installation of C. difficile toxins A and B (TcdA/B). Colonic tissue was collected at various timepoints following TcdA/B exposure to assess gene expression (qPCR), cytokine production (ELISA) and immune cell responses (flow cytometry). Knockout mice and neutralizing antibodies were used to deplete cytokines or cells.ResultsExaminion of colonic gene expression at different times following TcdA/B exposure found a dominant transcriptional signature related to neutrophil adhesion and diapedesis. In addition to the typical neutrophil chemokines Cxcl1 and Cxcl2, TcdA/B exposure also increased expression of neutrophil effector genes including Elane (neutrophil elastase). Neutrophil influx in response to TcdA/B was a critical driver of intestinal injury as antibody-mediated depletion of neutrophils lead to significantly less damage in the colon following TcdA/B exposure. Along with neutrophil influx, there were high levels of antimicrobial gene expression in the colon after TcdA/B exposure including RegIIIγ, S100a8, and Socs3, all genes regulated by IL-22. Upon further investigation, IL-22 was a significant mediator in the host response to TcdA/B exposure as it was upregulated >150-fold in the colon and originated from type 3 innate lymphoid cells (ILC3). Further, TcdA/B exposure in IL-22-/- mice lead to significantly more colonic damage compared to wildtype (WT) mice. Subsequent screening of previously published RNAseq data from IL-22-treated mouse colonic organoids identified various upregulated proteins involved in immune regulation, including the gene Slpi that encodes a protein (secretory leukocyte peptidase inhibitor) that inhibits leukocyte proteases, including neutrophil elastase. While TcdA/B challenge robustly induced the expression of Slpi in the colon of WT mice, IL-22-/- mice failed to express increased levels of Slpi and had greater levels of neutrophil elastase activity in the colon.ConclusionsTogether these data suggest a stepwise immune response to TcdA/B where ILC3 produce IL-22 to induce epithelial release of SLPI that attenuates the damaging effects of early neutrophil responses. Strategies to upregulate IL-22 may help control damage triggered by CDI and promote resolution of injury.Funding AgenciesLloyd Sutherland Chair in GI Research, Canadian Research Chair

Geriatric nutritional risk index as a risk-factor for Clostridioides difficile infection relapse in elderly Japanese patients.

Objective: Old age is a risk factor for Clostridioides difficile infection (CDI). As the world's aging population increases, identifying risk factors for CDI in elderly patients is a matter of urgency. This study examined the relationship between CDI relapse and nutritional status using the geriatric nutritional risk index (GNRI). Patients and Methods: Between January 2016 and December 2021, 108 patients were diagnosed with CDI. Of the 108 patients, 19 were excluded because of younger age (<65 years), early death within 14 days of the initial CDI diagnosis, and insufficient data. The patients were divided into low- (<75) and high-GNRI groups (≥75) based on the receiver operating characteristic curve analysis. Variables associated with CDI relapse were also analyzed. Results: The median GNRI scores in all patients and in the low- and high-GNRI groups were 74.9, 68.9, and 83.9, respectively. Of the 89 patients, 28 (31.8%) experienced a CDI relapse. The log-rank test showed a significantly better relapse-free survival (RFS) in the high GNRI group (P=0.002). Univariate analysis revealed that low GNRI (P=0.004), chronic kidney disease (CKD) (P=0.004), and beta-lactamase inhibitor administration before the initial diagnosis of CDI (P=0.025) were significantly correlated with RFS. Multivariate analysis revealed that low GNRI (P=0.008) and CKD (P=0.010) were independent prognostic factors for RFS. Conclusion: Among elderly patients, a low GNRI was strongly associated with CDI relapse. Our study may help clinicians to consider therapeutic strategies for elderly patients with CDI.

Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p=.009) and recurrence (p=.014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p=.01). Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.

762. Real-World Utilization of C. difficile Drug Treatments and Associated Clinical Outcomes in a US Hospital System

BackgroundIDSA recommends use of fidaxomicin or oral vancomycin for treatment of initial episode or first recurrence of Clostridioides difficile infection (CDI). This study aimed to evaluate impact of a clinical decision support order set driving appropriate use of fidaxomicin on utilization of CDI drug treatments and associated clinical outcomes. MethodsThis was a retrospective, quasi-experimental study evaluating CDI therapies pre- (8/2016-11/2017) and post- (5/2018-1/2020) CDI order set implementation at a level-one trauma center located in Virginia. Admitted adult patients were included if CDI testing was positive for a 1st or 2nd episode and received active CDI treatment. Exclusions included fulminant CDI and CDI diagnosis by PCR with < 3 bowel movements or laxative use within 24 hours. The primary outcome was CDI recurrence within 30 days of completing therapy in patients who achieved clinical cure. Secondary outcomes were evaluated at 30 and 90 days and included sustained response and CDI-related readmissions. ResultsAfter screening, 186 patients in the pre-group and 187 in the post-group were included. Median age was 68 [59-77], most patients had an initial CDI episode (88.2%) and were diagnosed with severe CDI (50.7%). Baseline characteristics were similar between each group on Charlson comorbidity index, ICU admission, CDI risk factors, and concomitant antibiotic use. Primary treatment options in the pre-group were most commonly metronidazole 47.9% and oral vancomycin 50.5%, and in the post-group were fidaxomicin 56.7% and oral vancomycin 41.7% (Figure 1). CDI recurrence rates at 30 days post-index medication (17.2% vs. 6.3%, p=0.004) were lower in the post-group (Table 1). Clinical cure (84.4% vs. 94.1%, p=0.002) and sustained response at 90 days (55.9% vs. 73.3%, p< 0.001) were higher in the post-group. CDI recurrence rates at 90 days and CDI-related readmissions at 30 and 90 days were also lower in the post group.Figure 1. CDI Treatment Utilization Table 1. Clinical Outcomes ConclusionImplementation of the CDI order set increased fidaxomicin use and was associated with a decrease in CDI recurrences and CDI-related readmissions and increase in clinical cure and sustained response. Findings suggest increased first-line use of fidaxomicin results in better clinical outcomes.Disclosures Lauren McDaniel, Pharm.D., BCIDP, Merck Sharp & Dohme Corp (Grant/Research Support) Nathan Everson, Pharm.D., BCIDP, AAHIVE, Merck & Co. (Grant/Research Support) Melissa White, PharmD, Merck Sharpe & Co (Grant/Research Support) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Yiyun Chen, PhD, Merck & Co., Inc (Employee) Rose Kohinke, PharmD, Merck Sharpe & Co (Research Grant or Support)

Challenges in the Diagnosis and Management of Recurrent and Severe Clostridioides difficile Infection in Children.

Children with Clostridioides difficile infection (CDI) can experience recurrent or severe disease. Recurrent CDI occurs in 20%-30% of children with an initial CDI episode. A careful clinical evaluation is important to distinguish recurrent CDI from other disorders that cause recurring gastrointestinal symptoms. Multiple treatment options exist for recurrent CDI, but the optimal therapeutic approach remains undefined. Severe or fulminant CDI can result in poor outcomes and significant morbidity in children. Since there is not a validated definition for severe CDI in children, physicians must use their clinical judgment to identify patients with severe CDI to institute appropriate therapy. In this review, we describe the diagnostic and management challenges in caring for children with recurrent and severe CDI.

Oral Vancomycin Prophylaxis for Clostridioides difficile

Oral Vancomycin Prophylaxis for <i>Clostridioides difficile</i>