Fulminant Clostridioides Difficile Infection Research Articles

Fidaxomicin versus oral vancomycin for Clostridioides difficile infection among patients at high risk for recurrence based on real-world experience.

Clostridioides difficile infection (CDI) is a common nosocomial infection and is associated with a high healthcare burden due to high rates of recurrence. In 2021 the IDSA/SHEA guideline update recommended fidaxomicin (FDX) as first-line therapy. Our medical center updated our institutional guidelines to follow these recommendations, prioritizing FDX use among patients at high risk for recurrent CDI (rCDI). This pre- post- quasi-experimental study included patients with a presumptive diagnosis of CDI at risk for recurrence (age >/= 65 years, immunocompromised, severe CDI) that received vancomycin (VAN) or FDX between October 2019 to October 2022. Patients who received bezlotoxumab, had fulminant CDI, or received <10 days of the same antibiotic for their full treatment course were excluded. Patients were evaluated for rCDI within 8 weeks of completion of therapy, subsequent episodes of CDI within 12 months, and CDI-related admissions within 30 days. Of 397 CDI regimens evaluated, 196 received VAN and 201 received FDX. Rates of rCDI (9.2% vs 10%, P = 0.86), subsequent CDI within 12 months of therapy completion of therapy (19.4% vs 26%, P = 0.12) and 30-day CDI-related readmissions (3% vs 4.5%, P = 0.6) were similar between patients who received VAN versus FDX. Outcomes were similar between patients treated with FDX and VAN for the treatment of CDI among those at high risk for rCDI, using our outlined criteria. Although we observed a trend toward lower rates of rCDI among immunocompromised patients, this finding was not significant. Further investigation is needed to determine which patients with CDI may benefit from FDX.

Clinical Characteristics and Cycle Thresholds Among Discordant and True Positive Test Results for Clostridiodes difficile

Background: The diagnosis of Clostridioides difficile infection (CDI) is challenging. Despite guideline-directed, multistep testing algorithms and diagnostic stewardship, the treatment of C. difficile colonization persists. The testing algorithm at our system utilizes an initial real-time PCR test (PCR) for Toxin B gene, which if positive, reflexes to an enzyme immunoassay (EIA) for detecting Toxins A and B. Discordant results (PCR +/EIA -) are suggestive of colonization, but the majority of patients with discordant results are treated for CDI. Correlation of C. difficile EIA B polymerase chain reaction (PCR) cycle thresholds (Ct) with the presence of free EIA and disease severity has been observed, but the ability to use Ct in the decision to treat patients with discordant results is unclear. Our study assesses if Ct values and other clinical characteristics favor treatment in select patients with discordant Methods: A retrospective chart review was performed of adult patients (≥ 18-year-old) with positive C. difficile PCR results that were admitted to our health system between June 01 and August 31, 2023. C. difficile PCR and Ct results were obtained by Cepheid GeneXpert and Toxin A and B EIA results were obtained by Meridian Bioscience Immunocard. Patients with discordant (PCR+/EIA) and true positive (PCR+/EIA+) results were compared. We assessed demographics, past medical history, clinical characteristics, severity of illness, PCR Ct values, treatment, and clinical outcomes including: 30-day all-cause mortality and re-admission, and 60-day CDI repeat testing and treatment. Results Of the 122 patients identified, 89 patients had discordant results and 43 had true positive Results: Severity of illness and other clinical and laboratory characteristics were similar between both groups. Mean Ct values were significantly lower for true positive results compared to discordant results, 24.28 vs 29.27, respectively (p26 (p=.08). Of the patients with discordant results, 73 completed treatment for CDI and no difference in clinical outcomes was observed compared to patients with discordant results that were not treated. Conclusion Ct values were lower among patients with true positive results compared to patients with discordant Conclusion: There were no statistically significant different rates of severe or fulminant CDI among patients with discordant results and Ct values &lt; 26, although this finding may be limited by sample size and Ct may be helpful in deciding which discordant patients to treat.

Frailty is a predictor for worse outcomes in patients hospitalized with Clostridioides difficile infection.

Frailty has major health implications for affected patients and is widely used in the perioperative risk assessment. The Hospital Frailty Risk Score (HFRS) is a validated score that utilizes administrative billing data to identify patients at higher risk because of frailty. We investigated the utility of the HFRS in patients with Clostridioides difficile infection (CDI) to determine whether they were at risk for worse outcomes and higher healthcare resource utilization. Using the 2017 National Inpatient Sample, we identified all adults with a primary diagnosis of CDI. We classified patients into 2 groups: those who had an HFRS <5 (NonFrailCDI) and those with a score ≥5 (FrailCDI). We assessed differences in hospital outcomes and healthcare resource utilization based on frailty status. We identified 93,810 hospitalizations, of which 54,300 (57.88%) were FrailCDI. FrailCDI patients were at higher risk for fulminant CDI (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.6-2.3), requiring colectomy (OR 4.1, 95%CI 1.5-11.2), and inpatient mortality (OR 4.5, 95%CI 2.8-7.1). Furthermore, FrailCDI patients had higher odds of requiring Intensive Care Unit admission (OR 13.7, 95%CI 6.3-29.9) or transfer to another facility on discharge (OR 2.2, 95%CI 2.0-2.4), and had longer hospital stays and higher total charges when compared with NonFrailCDI. Frailty as defined by the HFRS is an independent factor for worse outcomes and higher healthcare utilization in adults admitted for CDI. Risk stratifying patients by frailty may improve outcomes.

Real-world effectiveness of fidaxomicin in patients at high risk of Clostridioides difficile recurrence.

Compare the real-world impact of fidaxomicin (FDX) and vancomycin (VAN) on Clostridioides difficile infection (CDI) recurrence in a high-risk patient population. A retrospective, matched-cohort study evaluating hospitalized patients with CDI from January 1, 2016, to November 1, 2022, within a tertiary academic medical center. Adult patients with at least 1 prior CDI case who received either FDX or VAN for non-fulminant CDI while admitted, and had at least 1 additional risk factor for recurrence. Risk factors included age >70, solid organ or bone marrow transplant recipients, broad-spectrum antibiotic use within 30 days, or receipt of chemotherapy/immune-modulating agents within 30days of admission. FDX and VAN patients were matched according to risk factors. A total of 415 patient admissions were identified. After the exclusion of 92 patients for fulminant CDI, diarrhea from another cause, or use of VAN taper therapy, and 15 unmatched patients, 308 patient admissions were included (68 FDX and 240 VAN patients). There were no significant differences in 4-week recurrence (26% vs 23%; OR 1.1; P = .51), 90-day CDI readmission (29% vs 23%; P = .65), or 90-day all-cause readmission (54% vs 53%; P = .91). There was a significant 17% decrease in 90-day mortality associated with the use of FDX (OR .3; P = .04). In a real-world high-risk patient population, the use of FDX compared to oral VAN did not result in decreased CDI recurrence within 4 weeks or fewer hospital readmissions within 90 days. Further research is needed to better assess the value of FDX in this patient population.

673. Sniffing Out Adherence: Evaluation of a Clostridioides difficile guideline at a Tertiary Academic Medical Center

Abstract Background Tufts Medical Center’s (TMC) Antimicrobial Stewardship Team (AMT) in collaboration with gastroenterology (GI) developed an institutional treatment algorithm to guide appropriate inpatient management of Clostridioides difficile infection (CDI). The CD treatment algorithm was revised in April 2022 to reflect updated national clinical practice guidelines and disseminated to TMC providers. Our study aimed to assess provider compliance to TMC’s CD treatment algorithm. Methods A retrospective study of adult patients hospitalized from April 15, 2022 to October 31, 2022 and tested for CD was conducted. We collected patient demographics, white blood cell count, serum creatinine (SC), length of stay, CD treatment, Infectious Diseases (ID) &amp; GI consult, occurence of severe CDI (defined as white blood cell &amp;gt; 15 K/uL or SC &amp;gt; 1.5 mg/dL), occurrence of recurrent CDI, and immunocompromised status (defined by having had organ or bone marrow transplant, receiving immunomodulatory therapy or chronic steroids). A 2-step Clostridioides difficile (CD) testing algorithm was used. For CD toxin A/B &amp; glutamate dehydrogenase antigen (GDH) indeterminate results, reflex to nucleic amplification test (NAAT) was performed only with AMT approval. Results A total of 111 inpatients had CD toxin/GDH stool testing; 70 (63%) positive and 41 (37%) indeterminate. Of patients who had an indeterminate CD toxin/GDH, none had subsequent CD NAAT testing, and none receive CDI treatment. Of the others, 81 (73%), 23 (21%), and 7 (6%) were diagnosed with non-severe, severe, and fulminant CDI, respectively. The overall adherence to the institutional CD treatment algorithm was 58% (figure 1). More patients were appropriately treated with oral vancomycin (11, 65%) compared to those who were appropriately treated with fidaxomicin (9, 24%). Guidance adherence was (3) 38% among patients who had one or more recurrent episodes of CD, and none received suggested ID or GI consultation for additional CDI treatment consideration. Conclusion Adherence to institutional CD treatment algorithm was low. This study highlights opportunities to improve prescription of first line CDI therapy, especially among patients who are at higher risk for recurrence. Disclosures Maureen Campion, PharmD, BCIDP, Shinoigi: Speaker

Vancomycin vs metronidazole use for the treatment of Clostridioides difficile infection in a tertiary care hospital in Saudi Arabia

BackgroundThe 2017 Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) guidelines recommendation for oral vancomycin as preferred treatment was based on studies conducted in North America, Australia, and Europe. According to recent published data, metronidazole remains a reasonable option. No studies have been conducted in Saudi Arabia to compare prescribing patterns before and after the release of the guidelines. Due to low CDI burden in Saudi Arabia, the aim is to assess the effectiveness and outcomes of vancomycin vs metronidazole treatment options. MethodsThis was a retrospective cohort study conducted in a tertiary care hospital in Jeddah which was approved by the Institutional Review Board (IRB 2020–53). Data was collected from January 2017 to April 2020. Eligible patients were adults (>18 years old) diagnosed with CDI who either received oral metronidazole (500 mg 3 times daily) or oral vancomycin (125–500 mg 4 times daily). Patients who received a combination of treatment or who were diagnosed with fulminant CDI were excluded. Demographic data were collected. The primary outcome was to assess treatment response to initial therapy with oral metronidazole versus oral vancomycin. Secondary outcomes included assessing early treatment response, time to discharge after diagnosis, proportion of patients with a positive VRE surveillance culture within 6 months of diagnosis, 30-day recurrence and 30-day all-cause mortality. Chi-square or Fisher's exact test were used to examine differences in categorical variables while student t-test or Mann–Whitney test, were used to examine differences in continuous variables. P value < 0.05 was considered as significant. ResultsA total of 166 patients were included in the analysis. Demographic characteristics were not significantly different between the two groups. There was no difference in treatment response between vancomycin and metronidazole (96.4 % versus 94.3 %, p = 0.682). However, compared with metronidazole, vancomycin treatment was significantly associated with better early response (94.0 % versus 77.8 %, p = 0.008). Other outcomes were not significantly different between the two drug groups for time to discharge after diagnosis (P = 0.522), 30-day recurrence (P > 0.99) and 30-day all-cause mortality (P = 0.782). Of note, the vancomycin versus metronidazole use before the 2017 IDSA guidelines (26 % versus 74 %) was completely reversed after the release of the guidelines (83.3 % versus 16.7 %), p < 0.001). ConclusionThe results of this study demonstrate that vancomycin and metronidazole have comparable outcomes in regards to treatment response for non-fulminant CDI. The study also reveals the high and quick impact of international guidelines on local prescription patterns. Further studies are needed in Saudi Arabia to guide the treatment of CDI.

Clinical characteristics and outcomes of Clostridioides difficile infection in the intensive care unit: a KASID multi-centre study

Despite the growing clinical and economic burden of Clostridioides difficile infection (CDI), data on CDI in the intensive care unit (ICU) in the Asia-Pacific region are lacking. This retrospective study analyzed 191 patients who were treated with CDI in the ICUs of three hospitals in South Korea from January 2017 to May 2021. Backward-stepwise multiple logistic regression was used to identify factors influencing the treatment response and mortality. Fifty-eight patients (30.4%) were considered immunocompromised. The mean Charlson comorbidity index was 5.65 ± 2.39 (10-year survival rate: 21%), the APACHE II score was 20.86 ± 7.78 (mortality rate: 40%), the ATLAS score was 5.45 ± 1.59 (cure rate: 75%), and the SOFA score was 7.97 ± 4.03 (mortality rate: 21.5%). Fifty-eight (30.4%) of the CDI cases were severe and 40 (20.9%) were fulminant. Oral vancomycin or oral metronidazole was the most frequently first-line treatments (n = 57; 32.6%). The 10-day response rate was 59.7% and the 8-week overall mortality rate was 41.4%. Fulminant CDI (OR 0.230; 95% CI 0.085-0.623) and each 1 unit increment in the SOFA score (OR 0.848; 95% CI 0.759-0.947) were associated with treatment failure. High APACHE II (OR 0.355; 95% CI 0.143-0.880) and SOFA (OR 0.164; 95% CI 0.061-0.441) scores were associated with higher mortality. High-risk patients in the ICU had a higher mortality rate and a lower cure rate of CDI. Further research is required to provide more accurate prediction scoring systems and better clinical outcomes.

Total Abdominal Colectomy Versus Diverting Loop Ileostomy and Antegrade Colonic Lavage for Fulminant Clostridioides Colitis: Analysis of the National Inpatient Sample 2016–2019

BackgroundWhen surgery is indicated for fulminant Clostridioides difficile infection (CDI), total abdominal colectomy (TAC) is the most common approach. Diverting loop ileostomy (DLI) with antegrade colonic lavage has been introduced as a colon-sparing surgical approach. Prior analyses of National Inpatient Sample (NIS) data suggested equivalent postoperative outcomes between groups but did not evaluate healthcare resource utilization. As such, we aimed to analyze a more recent NIS cohort to compare these two approaches in terms of both postoperative outcomes and healthcare resource utilization. MethodsA retrospective analysis of the NIS from 2016 to 2019 was conducted. The primary outcome was postoperative in-hospital morbidity. Secondary outcomes included postoperative in-hospital mortality, system-specific postoperative complications, total admission cost, and length of stay (LOS). Univariable and multivariable regressions were utilized to compare the two operative approaches. ResultsIn total, 886 patients underwent TAC and 409 patients underwent DLI with antegrade colonic lavage. Adjusted analyses demonstrated no difference between groups in postoperative in-hospital morbidity (aOR 0.96, 95%CI 0.64–1.44, p = 0.851) or in-hospital mortality (aOR 1.15, 95%CI 0.81–1.64, p = 0.436). Patients undergoing TAC experienced significantly decreased total admission cost (MD $79,715.34, 95%CI 133,841–25,588, p = 0.004) and shorter postoperative LOS (MD 4.06 days, 95%CI 6.96–1.15, p = 0.006). ConclusionsThere are minimal differences between TAC and DLI with antegrade colonic lavage for fulminant CDI in terms of postoperative morbidity and mortality. Healthcare resource utilization, however, is significantly improved when patients undergo TAC as evidenced by clinically important decreases in total admission cost and postoperative LOS.

Fecal microbiota transplantation as potential first-line treatment for patients with Clostridioides difficile infection and prior appendectomy.

Clostridioides difficile infection (CDI) is a global health problem. The association of appendectomy on the severity and prognosis of CDI has been reported in many literatures, but there are still contradictions. In a retrospective study entitled "Patients with Closterium diffuse infection and prior appendectomy may be prone to word outcomes" published in World J Gastrointest Surg 2021, the author found that prior appendectomy affects the severity of CDI. Appendectomy may be a risk factor for increasing the severity of CDI. Therefore, it is necessary to seek alternative treatment for patients with prior appendectomy when they are more likely to have severe or fulminant CDI.

Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.

Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.

Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.

390. Eravacycline combination therapy for severe, recurrent, or fulminant Clostridioides difficile infection

Abstract Background Eravacycline (ERV) is a fluorocycline with in vitro activity against Clostridioides difficile infection (CDI). The purpose of this study was to evaluate the usage of ERV in the management of CDI. Methods IRB-approved, retrospective case series in a health system that added ERV to formulary in 9/2019. All patients between 9/2019 and 2/2020 treated with adjunctive ERV for &amp;gt; 24 hours for severe, recurrent, or fulminant CDI were included. Exclusion criteria: pregnant, age &amp;lt; 18 years. Primary outcome: all-cause mortality at 30 days (d) from start of ERV. Secondary outcomes: clinical cure, colectomy, and recurrence within 30 d. Data was reported using descriptive statistics and measures of central tendency. Results 14 patients included: severe (4, 29%), recurrent (4, 29%), and fulminant CDI (6, 43%) (table 1). Infectious diseases consult: 14/14, median time to consult 1 (1, 2) d. Surgery consult: 1 severe and 5 fulminant CDI cases, median time to consult 1 (1, 3) d. Prior to ERV initiation, 10 patients were on oral vancomycin (PO VAN) and intravenous metronidazole (IV MTZ), one was on PO VAN, two were on IV MTZ, and one was on no CDI therapy. After ERV was initiated, six patients were on ERV, PO VAN, and IV MTZ combination and eight patients were on ERV and PO VAN concurrently. The reason for using ERV was fulminant CDI (6, 42.8%), severe CDI (4, 29%), unable to tolerate other CDI medications (3, 21%), refractory CDI (3, 21%), and recurrent CDI (1, 7%). Time to eravacycline initiation 1.5 d (1, 3.75) with median duration of 6 d (4.5, 7.75). 30-day all-cause mortality 2 (14%), all were in-hospital; 1 (7%) hospice. Clinical cure occurred in 12 (86%). Two (14%) required colectomy; one received surgery on the same day of CDI diagnosis and ERV initiation and the other had surgery 4 days before ERV initiation. Two patients with recurrent CDI received fecal microbiota transplant outpatient, one of which also received bezlotoxumab. Zero recurrences and one readmission within 30 d. Table 1.Patient demographics, severity, and clinical outcomes Conclusion ERV appears to be a potential adjunctive therapy for severe, recurrent, or fulminant CDI. Prospective studies are needed to further investigate the safety and efficacy of ERV in serious CDI. Disclosures All Authors: No reported disclosures.

Fecal microbiota transplantation may reduce the mortality of patients with severe and fulminant Clostridioides difficile infection compared to standard-of-care antibiotics in a community hospital.

Clostridioides difficile infection (CDI) is known for significant morbidity and mortality. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent and resistant CDI. However, its impact on the mortality rate of patients with severe and fulminant CDI has not been rigorously studied yet. We aimed to evaluate the effectiveness of FMT on the mortality rate of patients with severe or fulminant CDI in a community hospital system. Our study included 106 inpatients with severe or fulminant CDI. Both standard-of-care (SOC) and FMT were provided to 14 (13.2%) patients (the FMT group). SOC antibiotics alone were provided to 92 (86.8%) patients, out of whom 28 patients were included via propensity score matching in a 2:1 ratio (the SOC group). The primary outcome was defined as the composite end-point of mortality during admission, within 30 and 90 days after discharge, and discharge with comfort measures only. Each component was a secondary end-point. The primary outcome rate in the FMT group was 7.1% (1/14) compared to 25.0% (7/28) in the SOC group. Univariate analysis demonstrated that FMT decreases mortality (odds ratio[OR] 0.08, 95% confidence interval [CI] 0.01-0.58, P=0.01). However, multivariate regression did not show statistical significance (OR 0.15, 95% CI 0.01-2.53, P=0.19), possibly due to the small sample size. FMT may decrease the mortality of patients with severe and fulminant CDI. Large studies are needed to validate these findings.

A High-Carbohydrate Diet Prolongs Dysbiosis and Clostridioides difficile Carriage and Increases Delayed Mortality in a Hamster Model of Infection.

ABSTRACTStudies using mouse models of Clostridioides difficile infection (CDI) have demonstrated a variety of relationships between dietary macronutrients on antibiotic-associated CDI; however, few of these effects have been examined in more susceptible hamster models of CDI. In this study, we investigated the effect of a high-carbohydrate diet previously shown to protect mice from CDI on the progression and resolution of CDI in a hamster disease model, with 10 animals per group. Hamsters fed the high-carbohydrate diet developed distinct diet-specific microbiomes during antibiotic treatment and CDI, with lower diversity, persistent C. difficile carriage, and delayed microbiome restoration. In contrast to CDI protection in mice, most hamsters fed a high-carbohydrate diet developed fulminant CDI including several cases of late-onset CDI, that were not observed in hamsters fed a standard lab diet. We speculate that prolonged high-carbohydrate diet-specific dysbiosis in these animals allowed C. difficile to persist in the gut of the animals where they could proliferate postvancomycin treatment, leading to delayed CDI onset. This study, along with similar studies in mouse models of CDI, suggests some high-carbohydrate diets may promote antibiotic-associated dysbiosis and long-term C. difficile carriage, which may later convert to symptomatic CDI.IMPORTANCE The effects of diet on CDI are not completely known. Here, we used a high-carbohydrate diet previously shown to protect mice against CDI to assess its effect on a hamster model of CDI and paradoxically found that it promoted dysbiosis, C. difficile carriage, and higher mortality. A common thread in both mouse and hamster experimental models was that the high-carbohydrate diet promoted dysbiosis and long-term carriage of C. difficile, which may have converted to fulminant CDI only in the highly susceptible hamster model system. If diets high in carbohydrates also promote dysbiosis and C. difficile carriage in humans, then these diets might paradoxically increase chances of CDI relapse despite their protective effects against primary CDI.

Fulminant Clostridioides difficile Infection: A Review of Treatment Options for a Life-Threatening Infection.

Fulminant Clostridioides difficile infection (FCDI) encompasses 3 to 5% of all CDI cases with associated mortality rates between 30 and 40%. Major treatment modalities include surgery and medical management with antibiotic and nonantibiotic therapies. However, identification of patients with CDI that will progress to FCDI is difficult and makes it challenging to direct medical management and identify those who may benefit from surgery. Furthermore, since it is difficult to study such a critically ill population, data investigating treatment options are limited. Surgical management with diverting loop ileostomy (LI) instead of a total abdominal colectomy (TAC) with end ileostomy has several appealing advantages, and studies have not consistently demonstrated a clinical benefit with this less-invasive strategy, so both LI and TAC remain acceptable surgical options. Successful medical management of FCDI is complicated by pharmacokinetic changes that occur in critically ill patients, and there is an absence of high-quality studies that included patients with FCDI. Recommendations accordingly include a combination of antibiotics administered via multiple routes to ensure adequate drug concentrations in the colon: intravenous metronidazole, high-dose oral vancomycin, and rectal vancomycin. Although fidaxomicin is now recommended as first-line therapy for non-FCDI, there are limited clinical data to support its use in FCDI. Several nonantibiotic therapies, including fecal microbiota transplantation and intravenous immunoglobulin, have shown success as adjunctive therapies, but they are unlikely to be effective alone. In this review, we aim to summarize diagnosis and treatment options for FCDI.

Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort.

Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients. To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class. We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT. Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1years, range 7-95years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT. Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.

Incidence and Outcomes Associated With Clostridioides difficile Infection in Solid Organ Transplant Recipients

Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients. To estimate the CDI incidence and outcomes in SOT recipients. A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period. The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis. Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality. In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

98. Outcomes of Clinical Decision Support for Outpatient Management of Clostridioides difficile Infection

BackgroundOur antimicrobial stewardship program identified high rates of suboptimal metronidazole prescribing for Clostridioides difficile infection (CDI) within ambulatory clinics. An outpatient best practice advisory (BPA) was implemented to notify prescribers “Vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI. MethodsWe conducted an IRB approved quasi-experiment before and after implementation of the BPA on June 3, 2020. Inclusion: Adult patients diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between 11/1/2019 and 11/30/2020. Exclusion: fulminant CDI. Primary endpoint: guideline-concordant CDI therapy, defined as oral vancomycin or fidaxomicin. Oral metronidazole was considered guideline-concordant if prescribed due to cost barrier. Secondary endpoints: reasons for alternative CDI therapy, patient outcomes, prescriber response to the BPA. Descriptive and bivariate analyses were completed.Results189 patients were included in the study, 92 before and 97 after the BPA. Median age: 59 years, 31% male, 75% Caucasian, 30% with CDI-related comorbidities, 35% with healthcare exposure, 65% with antibiotic exposure, 44% with gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 out of 26 times and optimized the therapy of 16 patients in six months. Guideline-concordant therapy increased after implementation of the BPA (72% vs. 91%, p=0.001) (Figure 1). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA (Figure 2). Reasons for alternative CDI therapy included medication cost, lack of insurance coverage, and non-CDI infection. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs. 7%, p< 0.001). Figure 1. Guideline-concordant CDI therapy Figure 2. Specific CDI therapy ConclusionClinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.Disclosures Susan L. Davis, PharmD, Nothing to disclose Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

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)

A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection.

Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.