CDI Episodes Research Articles

2374. Healthcare Resource Use, Costs, and Recurrences in Patients with Clostridioides difficile Infection: A Real-world Data Analysis

Background Clostridioides difficile infection (CDI), especially recurrent CDI (rCDI), is associated with high morbidity and resource use and imposes a significant burden on the US healthcare system. The objective of this study was to evaluate the burden of rCDI on healthcare resource utilization.MethodsA retrospective study analyzed commercial claims data from patients aged 18–64 years old in the IQVIA PharMetrics Plus™ database. CDI episodes required an inpatient stay with CDI diagnosis code (ICD-9-CM 008.45; ICD-10-CM A04.7, A04.71, A04.72), or an outpatient medical claim with CDI diagnosis code plus a CDI treatment, and index episodes occurred from January 1, 2010 to June 30, 2017. Only patients who were observable 6 months before and 12 months after the index CDI episode were included. Each CDI episode was followed by a 14-day claim-free period after the end of treatment. rCDI was defined as another CDI episode within an 8-week window immediately after the claim-free period. Number of CDI and rCDI episodes, healthcare resource use, and costs were calculated over 12-month follow-up and stratified by number of rCDI episodes. Costs were adjusted to 2018 dollars.Results46,571 patients with an index CDI episode were included, with 3,129 (6.7%) who had 1 rCDI, 472 (1.0%) who had 2 rCDI, and 134 (0.3%) who had 3+ rCDI episodes. Mean age was 47.4 years, and 62.4% were female. In the 12-month follow-up, the mean (SD) numbers of inpatient visits were 1.4 (2.1) for those with no rCDI, 2.7 (3.4) for those with 1 rCDI, 3.7 (3.9) for those with 2 rCDI, and 5.8 (6.0) for those with 3+ rCDI episodes. Emergency department (ED) visits had a similar trend, with mean (SD) number of visits of 1.5 (3.5), 2.5 (6.0), 3.7 (7.0), and 4.6 (13), respectively for the four study groups. All-cause costs after the index CDI were $71,980 for those with no rCDI, $131,953 for those with 1 rCDI, $180,574 for those with 2 rCDI, and $207,733 for those with 3+ rCDI.ConclusionCDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. During the 12 months after an index CDI episode, the number of inpatient admissions and ED visits increased substantially for patients with an rCDI episode. Direct medical costs for patients with rCDI also increased with number of recurrences.Disclosures All authors: No reported disclosures.

2436. Real-world Evidence of Fecal Microbiota Transplant Use and Outcomes in Patients with Clostridioides difficile Infection

Background Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are associated with substantial economic burden, quality-of-life impairment, and increased morbidity and mortality. Fecal microbiota transplant (FMT) is an investigational, non-antibiotic approach to attempt to prevent recurrences in patients with multiple CDI. In controlled trials, efficacy rates of 62–76% have been reported with a single FMT, and up to 90% with multiple FMTs. This study evaluated real-world outcomes in patients with CDI, most of whom had a single FMT.MethodsData from the Optum® de-identified Integrated Claims-Clinical dataset were extracted for patients with a first-observed CDI diagnosis between 4/2011 and 3/2018 that occurred within ±7 days of initial CDI antibiotics. Each patient had a > = 4-year look-back period with no CDI claims prior to the index episode. rCDI was defined as a subsequent antibiotic prescription between 7 and 365 days after the prior CDI episode. The proportion of patients with rCDI, use of FMT, and recurrences after FMT were reported.ResultsOf the 98,895 patients included in the analysis, 71,189 (72.0%) had one CDI episode, 27,706 (28.0%) had > = 1 rCDI, and 10,233 (10.4%) had multiple rCDI. The mean age was 64.2 years (56% > = 65 years), and 61% were female. Medicare was used by 48% of patients, and commercial insurance was used by 32%. A total of 522 (0.5%) patients (mean age, 61.9 years) received a total of 541 FMT procedures. 36% of the FMT procedures occurred after the first observed CDI episode, 22% after the 1st rCDI, and 42% after the second and/or subsequent rCDI episode. Of those who received FMT, 71.4% (n = 373) of patients had no subsequent CDI events by 3/2018.ConclusionAs an investigational procedure, only a very small proportion of patients with CDI were identified as undergoing FMT, and the timing of the procedure for some patients may not have aligned with current guidance. This study provides data on real-world efficacy outcomes after a single FMT, with an efficacy rate of 71.4%, which is consistent with rates reported in controlled trials. A small number of patients received more than one FMT procedure, potentially due to treatment failures. Further research is needed to examine potential improvements in efficacy with multiple FMTs.Disclosures All authors: No reported disclosures.

2415. Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infections among High-risk Patients

Background Clostridium difficile infection (CDI) is associated with high rates of recurrence, and major risk factors for recurrence include prior CDI episode(s) and antibiotic exposure. Prior studies concluded a reduction in CDI recurrence using oral vancomycin for prophylaxis (ppx), but were limited by prescriber bias and inclusion of all hospitalized adult patients with prior CDI and receipt of systemic antibiotics. We sought to determine whether or not oral vancomycin prophylaxis reduced CDI recurrence in high-risk patients.MethodsThis retrospective cohort study included patients > 2 years of age who had at least 2 episodes of CDI within the last year prior to broad-spectrum antibiotic exposure. The ppx cohort included patients who received oral vancomycin for > 50% of the duration of broad-spectrum antibiotic therapy, and the no ppx cohort included patients who received no oral vancomycin while on broad-spectrum antibiotics. Cohorts were compared via a univariate analysis. A Kaplan–Meier analysis was used to evaluate the time-to-event for development of CDI.ResultsOf 108 patients who met inclusion criteria, 88 patients were included in the no ppx cohort and 20 patients in the ppx cohort. The primary outcome of CDI incidence was numerically lower in the ppx cohort [13 (14.8%) vs. 2 (10%), p = 0.733]. Secondary outcomes within 12 weeks of broad-spectrum antibiotic initiation were similar between cohorts. The mean time from broad-spectrum antibiotic initiation to CDI recurrence was longer among the ppx cohort, suggesting a delay in time to CDI recurrence (29 + 25.9 vs. 57.5 + 26.1 days, p = 0.171). This delay led to a lower incidence of hospital acquired (HA) CDI in the ppx cohort [4 (30.8%) vs. 0 (0%), P > 0.99]. The Kaplan–Meier analysis (Figure 1) demonstrated no significant difference in time-to-event of CDI, p = 0.70.ConclusionThe use of oral vancomycin for secondary ppx of CDI was not shown to have a statistically significant difference in CDI recurrence compared with no ppx in this study. However, this may be due to the low sample size in the ppx cohort and low CDI event rates. The trend toward a delay in CDI recurrence and reduction in HA-CDI with the use of oral vancomycin is hypothesis generating. Further controlled studies are warranted to confirm the role of oral vancomycin for secondary ppx of CDI. Disclosures All authors: No reported disclosures.

2401. Epidemiology of Clostridium difficile Infection in Intestinal and Multivisceral Transplant Patients at a Single Transplant Center

Background Clostridium difficile infection (CDI) is the leading cause of infectious diarrhea in the healthcare setting. Solid-organ transplant (SOT) recipients are at increased risk compared with the general hospitalized population (7.4–20% vs. 0.9%). Our center recently expanded its intestinal and multivisceral transplant (IMVT) program, providing the opportunity to examine the epidemiology of CDI in this vulnerable population.MethodsWe conducted a retrospective study of all IMVT recipients between 2009 and 2018. CDI was defined as presence of diarrhea with a positive polymerase chain reaction (PCR) test for the toxin B gene. Early CDI constituted an episode of CDI within the first 6 months post-transplant. Data were collected on demographics, transplant characteristics, CDI episode, and outcomes.ResultsWe identified 86 patients who underwent a total of 94 transplants: 60 (64%) isolated intestinal transplants, 21 (22%) intestine/liver/pancreas, 10 (11%) intestine/pancreas, two (2%) intestine/liver/pancreas/kidney, and one (1%) intestine/kidney transplant. All but three patients received perioperative metronidazole. Four patients (5%) had CDI prior to transplant, but none of them recurred in the first 6 months post-transplant. Five patients developed a total of seven mild-moderate episodes of early CDI (attack rate = 5.9%). Three patients (60%) with early CDI developed rejection, similar to the incidence (70%) in patients without CDI. Two patients with early CDI developed recurrence; both underwent intestinal re-transplantation. One-year mortality was similar among patients with and without early CDI (20% vs. 23%).ConclusionCDI is associated with allograft loss, rejection, and mortality in some SOT recipients. Although limited by sample size, we observed that early CDI was not associated with those outcomes in our population. Multicenter studies are merited to explore risk factors for CDI and associations with outcomes in IMVT. Disclosures All authors: No reported disclosures.

2383. Epidemiological and Clinical Features of Clostridioides difficile Infections in Pediatric Oncology and Transplant Patients

Background Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated diarrhea-causing significant morbidity and mortality in adults. The epidemiology and clinical course of CDI in children, especially with cancer are poorly defined. We aim to describe the clinical, epidemiological features and outcomes of CDI, and identify risk factors for recurrence in a pediatric oncology centerMethodsThis is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by electronic medical record search for positive C. difficile PCR tests. CDI episodes were classified as incident, duplicate or recurrent and community-onset (CO), hospital-onset (HO), or community-onset healthcare facility associated (COHCFA) using National Healthcare Safety Network surveillance definitions. Demographics, underlying diagnosis, CDI characteristics, drug exposure, and outcomes were analyzed. Risk factors for CDI recurrence were assessed by logistic regression.ResultsOne hundred-eighty patients developed 305 CDI episodes; 233 (78%) were incident, 65 (22%) recurrent, and 7 duplicate and removed from the analysis. Recurrence occurred after 51 incident episodes (Table 1). Median age (range) was 5.7 (0.5–25.5) years. Underlying diagnoses were leukemia/lymphoma (56%) and solid/brain tumors (42%). 87 (29%) received HSCT. Almost all patients received antibiotics 4 weeks prior to CDI. 14% received laxatives 72 hours prior to CDI. 50% of patients were neutropenic. The median (range) duration of diarrhea was 10.0 (1–77). Thirty patients (15%) were hospitalized due to CDI, for a median (range) of 3 (1–49) days. 16% had a delay in chemotherapy due to CDI. There was no ICU admissions nor death due to CDI. None of the evaluated variables was identified as a significant risk factor for CDI recurrence by logistic regression (Table 3).ConclusionCDI in pediatric oncology and transplant patients ran a generally mild course, associated with chemotherapy delay and hospitalization in a small fraction, and no attributable ICU admission nor death. CDI recurred in less than a quarter of patients. Risk factors for CDI recurrence were not identified. DisclosuresRandall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board

2382. Recurrent Clostridioides difficile Infection (CDI) Worsens Anxiety-Related Patient-Reported Quality of Life

BackgroundThe Health-Related Quality of life (HR-QOL) instrument, the Cdiff32, allows studies on QOL changes associated with recurrent CDI. An ongoing real-world study of bezlotoxumab (BEZ) provided a unique opportunity to study anxiety-related HR-QOL in patients at high risk for recurrent CDI using the anxiety sub-domain of Cdiff32. The aims of this study were to assess baseline anxiety-related HR-QOL based on the number of prior episodes of CDI and to evaluate changes in patients with or without recurrence.MethodsPatients at high risk for recurrent CDI given BEZ were administered the anxiety sub-domain questions of the Cdiff32 prior to infusion and at approximately 90 days after administration (0 = worst anxiety; 100 = no anxiety). The number of prior episodes of CDI were collected, along with demographics and co-morbid conditions. Patients were followed for 90 days for CDI recurrence, which was defined as new onset of diarrhea requiring CDI-active antibiotics.ResultsThere were 107 patients evaluated, aged 68 ± 14 years (mean ± SD) with multiple co-morbid conditions (mean Charlson: 4 ± 3) and multiple previous CDI episodes (3 ± 1 episodes). Fourteen patients (13%) experienced a further CDI recurrence within 90 days following BEZ. Overall, baseline anxiety HR-QOL was 29 ± 22. Risk factors for lower baseline anxiety-related HR-QOL included immunocompromised conditions (P < 0.046) and receipt of a proton pump inhibitor (P < 0.018). Compared with patients with primary CDI disease (Score: 35 ± 20), baseline anxiety HR-QOL was worse with subsequent prior recurrences (Score: 26 ± 23) for CDI episodes 2–4, and then improved for subsequent episodes (Score: 38 ± 22). Anxiety-related HR-QOL improved by a mean of 32 ± 25 points compared with patients that experienced a further recurrence where HR-QOL declined (P < 0.0001). Results were confirmed in a multivariate model controlling for Charlson score and chronic renal failure.ConclusionPoor anxiety-related HR-QOL was observed at baseline in all patients regardless of number of prior episodes. QOL improved 90 days after BEZ infusion in patients without further recurrences of CDIs and worsened in patients with a subsequent recurrence.Disclosures All authors: No reported disclosures.

2432. Durability Against Antibiotics After Response to Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection

BackgroundFecal microbiota transplantation (FMT) cures ~90% of patients with recurrent Clostridioides difficile infection (rCDI). Ongoing or repeated exposure to risk factors, especially antibiotics (a modifiable risk factor but often necessary), may lead to future CDI. However, it is not known if FMT provides durable protection against future CDI despite subsequent antibiotic exposure. We studied the long-term durability of FMT against antibiotic exposure post-FMT.MethodsA retrospective cohort study of patients undergoing FMT via colonoscopy for rCDI from Sep 2012 - Jun 2018 was performed. Patients were followed up for 1 year after FMT; data regarding future CDI episodes (watery diarrhea with positive stool test after interim symptom resolution), healthcare exposure, systemic non-CDI antibiotics and acid blocker therapy were collected. Primary outcome was ‘durability’ of response to FMT (defined as no CDI within 1 year post-FMT). Descriptive statistics, Chi square test, Wilcoxon test and multivariate logistic regression were used as appropriate.ResultsThe study included 460 patients; median age 57 years (range 18–94 years), 65.2% (300) female. Overall 31.6% (144) received antibiotics; median number of courses of antibiotics, 2 (range 1–7). Of those who received antibiotics, the incidence of future CDI was 24.3% (n = 34), compared with 9% (n = 28) of those who did not receive antibiotics (P < .001). Median time to first CDI episode post-FMT was 103 (range 5–338) days. Incremental antibiotic courses did not lead to increased risk of future CDI (comparing 1, 2 or ≥3 courses, p = .68). In patients with antibiotic exposure, age and risk factors were similar in patients with and without future CDI (Table 1). Amongst those without antibiotic exposure, inflammatory bowel disease (IBD) predicted future CDI (p = .02). After controlling for risk factors and comorbidities, antibiotic use (p = .004) and IBD (p = .02) independently increased risk of future CDI.ConclusionThe majority of patients with rCDI have a durable response to FMT despite ongoing risk factors. These data suggest that three-fourth of patients who receive antibiotics after FMT do not develop future CDI. IBD and antibiotic exposure independently increase the risk of future CDI. Disclosures All authors: No reported disclosures.

LB5. A Long-Time Coming: Final 2-year Analysis of Efficacy, Durability, and Microbiome Changes in a Controlled Open-Label Trial of Investigational Microbiota-Based Drug RBX2660 for Recurrent Clostridioides difficile Infections

BackgroundRecurrent Clostridioides difficile infection (rCDI) is an urgent public health threat associated with significant mortality and medical cost. Microbiota therapy is gaining acceptance as a strategy to reduce rCDI recurrence. We present the final 24-month analysis of clinical safety, efficacy, and microbiome restoration from a Phase 2 open-label trial of RBX2660 for prevention of CDI recurrence.MethodsParticipants with multi-recurrent CDI received <2 doses of RBX2660 delivered via enema 7 days apart in this multicenter, open-label Phase 2 study. Efficacy was defined as the absence of CDI recurrence through 56 days after the last dose and was compared with 8-week recurrence-free rates for a historical control cohort that received standard-of-care antibiotic therapy. Fisher exact test compared the proportion of treatment participants who were CDI-free by age and sex. Durability was defined as continued absence of CDI episodes beyond 8 weeks. Safety and durability assessments occurred at 3, 6, 12, and 24 months. Participant stool samples were collected prior to and for up to 720 days after treatment, and microbiome changes were assessed by shallow shotgun sequencing.ResultsThe efficacy of RBX2660 to prevent rCDI at 8 weeks (78.9%; 112/142) was higher than the CDI-free rate in the historical control group (30.7%, 23/75; P < 0.0001). Age and sex did not impact efficacy. Among participants who achieved treatment success at 8 weeks and were evaluable for long-term durability (n = 95), 8 experienced a new CDI episode by the 24-month follow-up for an overall durability of 91.6%. The safety profile was consistent with previous reports for RBX2660. In total, 503 stool samples from 110 treatment responders were analyzed. Within 7 days of treatment, the relative abundance of Bacteroidia and Clostridia remained shifted higher than pre-treatment levels while Gammaproteobacteria and Bacilli declined sharply after treatment, and these changes persisted to at least 24 months.ConclusionRBX2660, a microbiota-based drug, was safe and efficacious for preventing rCDI with clinical durability to 24 months after treatment, independent of age or sex, and RBX2660 durability associated with durable microbiome shifts from pre-treatment to a healthier composition. DisclosuresRobert Orenstein, DO, Rebiotix Inc. (Advisor or Review Panel member), Sarah Mische, PhD, Rebiotix Inc. (Employee), Ken Blount, PhD, Rebiotix Inc. (Employee), Lindy Bancke, PharmD, Rebiotix Inc. (Employee), Xin Su, MD, MSci, Rebiotix Inc. (Employee), Dana Walsh, PhD, Rebiotix Inc. (Employee), Adam Harvey, PhD, Rebiotix Inc. (Employee), Carlos Gonzalez, MS, Rebiotix Inc. (Consultant), Dale N. Gerding, MD, Rebiotix Inc. (Board Member).

2419. Timing of Secondary Prophylaxis Against Clostridium difficile Infection After Antibiotic Exposure

Background Clostridium difficile infection (CDI) is the most common nosocomial infection, and is increasing. The major risk for CDI is antibiotic (abx) use. We have previously shown that secondary prophylaxis with vancomycin decreases CDI relapse in patients with recent CDI given abx to treat another infection. The median time to relapse after use of abx was 3 days. In an effort to further elucidate the best way to employ secondary prophylaxis against CDI, we examined all patients with CDI in our institution in 2016 and timing of relapse as related to another exposure to abx and the success of prophylaxis relative to the timing and the duration of prophylaxis.MethodsAll patients positive by PCR for C difficile at our institution in 2016 were examined for receipt of abx within 3 months of a positive PCR. The relapse rates for all patients, patients who received abx with or without secondary prophylaxis, and patients who did not receive abx were calculated. Timing of the relapse from the prior CDI and from receipt of abx were determined as was impact of prophylaxis, particularly in patients who relapsed despite prophylaxis.Results1748 patients were identified, representing 2181 episodes of CDI. The relapse rates and timing based on prior CDI, receipt of additional abx prior to relapse, and use of prophylaxis are shown in Table 1.Prophylaxis decreased the overall relapse rate from 19.2% to 11.6%. Time to relapse in patients who relapsed despite prophylaxis was significantly longer indicating prophylaxis was having an effect. The failure appears dependent on when prophylaxis was started relative to abx and how long prophylaxis was given relative to abx.ConclusionProphylaxis is effective in preventing relapses in patients given abx after CDI however the timing and duration of prophylaxis significantly impacts the effectiveness. The majority of CDI relapses after abx occur within 3 days and can be prevented by prophylaxis. Relapses that occur after 3 weeks appear unrelated to the use of abx and are not preventable through prophylaxis. Failures of prophylaxis within the first 1 week are likely related to starting prophylaxis too late after abx and failures that occur between 1 and 3 weeks after abx are likely related to ending prophylaxis too early. Disclosures All authors: No reported disclosures.

2376. Incidence of Clostridioides difficile Infection Among United States Medicare Advantage Enrollees

Background Clostridioides difficile infection (CDI) may be life-threatening, and individuals aged ≥ 65 years are at increased risk. CDI burden among Medicare fee-for-service enrollees and nursing home residents in the United States have been characterized previously. The present study aimed to describe the incidence of CDI among Medicare Advantage Enrollees (MAEs), who account for 34% of all Medicare beneficiaries with enrollment increasing annually since 2004.MethodsDe-identified claims data for this retrospective cohort study were collected from the Optum® Clinformatics® Data Mart and included MAEs aged ≥ 65 years with continuous enrollment for ≥ 1 year before January 1, 2016, followed through death or disenrollment. CDI incidence was defined using the International Classification of Diseases 9th Revision diagnosis code of 008.45 or 10th Revision code of A04.7 (other than admitting diagnosis) or by treatment with nontopical metronidazole, oral vancomycin, or fidaxomicin within 14 days of CDI test. Incident CDI cases were identified from January 1 to December 31, 2016, and required that no CDI occurred within the previous 60 days in 2016. Incidence in 2016 was calculated as CDI cases and CDI patients per 100,000 person-years (PY) of observation time.ResultsOf 2,542,341 MAEs analyzed, 15,201 patients (0.6%) experienced a total of 18,842 incident CDI episodes. Overall, incidence rates were 762.8 CDI cases and 616.5 CDI patients per 100,000 PY. Incidence increased with age (539.6, 847.3, and 1259.6 cases per 100,000 PY in patients aged 65‒74 years, 75‒84 years, and ≥ 85 years, respectively). Most episodes (50.9%) were community acquired; the remaining 37.7% and 11.4% of episodes were hospital acquired and indeterminate, respectively. CDI patients were more likely than non-CDI patients to be older (mean age, 78.3 vs. 76.1 years, P < 0.0001), be women (64.5% vs. 58.1%, P < 0.0001), or have comorbidities (mean Charlson comorbidity index score, 4.5 vs. 1.8, P < 0.0001).ConclusionCDI incidence rates in the Medicare Advantage population were similar to those reported previously in the Medicare fee-for-service population and nationally among adults aged ≥ 65 years. Data are consistent with a high CDI burden among older US adults.Funding: Pfizer.Disclosures All authors: No reported disclosures.

1984. A Multi-Disciplinary Team-based Quality Improvement Initiative to Reduce Clostridioides difficile Rates and Promote Antimicrobial Stewardship in Targeted Surgical Wards

BackgroundAt Stanford, two surgical wards, E3 and F3, were responsible for 1/5 of hospital-acquired Clostridioides difficile infection (HO CDI) cases in the fiscal year 2018 (FY2018). We used a quality improvement framework with a goal to reduce yearly HO CDI episodes by 1/2 on these wards.MethodsA multidisciplinary quality improvement team was created with frontline nursing leaders and representatives from colorectal surgery, gynecology oncology, antimicrobial stewardship (ASP), infection prevention, and pharmacy. Coaching and instruction on quality improvement were provided as part of Stanford’s “Realizing Improvement through Team Empowerment” (RITE) program. Using A3 problem solving, root cause analysis identified key drivers, and interventions were performed. Cumulative HO CDI cases in FY2019 and weekly antibiotic days of therapy (DOT) on E3/F3 were monitored.ResultsReview of FY2018 HO CDI cases (n = 14) revealed the most common key driver as inappropriate antibiotic prescribing (8 cases, 57%). Multiple interventions were instituted (Figure 1). Three ASP interventions began February 2019: nursing questioned antibiotic choice/duration on daily interdisciplinary rounds (Figure 2), automatic infectious disease consultation for > 72 hours of piperacillin/tazobactam on gynecology/oncology patients, and twice-weekly rounds between ASP and a colorectal attending. Data from ASP/colorectal rounds from March 19, 2019 to April 16, 2019 showed means of 18.2 minutes taken for chart review and 4.4 minutes for discussion. 25 charts reviewed led to 16 (64%) ASP recommendations and 14/16 (87.5%) of recommendations accepted. Common interventions included: appropriate duration of antibiotics, clarification of the team’s planned duration, and review of microbiology data to narrow therapy. Mean DOT decreased from 35.28 to 21.61 (39%) since July 2018 (Figure 3). Patient volume and case mix index remained stable throughout, suggesting no impact on DOT. Though CDI cases did not decrease, interventions were in place for only 2 months (Figure 4).ConclusionWhile too early to determine its impact on HO CDI rates, a multi-disciplinary team approach utilizing A3 problem solving was successful in implementing effective ASP measures including nursing-led ASP and structured antibiotic timeouts. Disclosures All authors: No reported disclosures.

2381. Epidemiology of Clostridium difficile Infection in Patients Receiving Interleukin-2 Therapy

Background Clostridium difficile infection (CDI) has been associated with interleukin-2 (IL2) therapy, possibly leading to unnecessary testing and treatment of colonized patients receiving IL2 therapy. Since the debut of IL2 therapy for renal cell carcinoma (RCC) and metastatic melanoma (MM), only one study with 6 patients has shown a relationship between CDI and IL2 treatment, and no mortality data were reported. Because of the rising concern for appropriate testing and treatment of CDI, further studies looking at the correlation between IL2 therapy and CDI are needed. This study aims to describe CDI rates among a larger cohort of IL2 treated patients and to include mortality data.MethodsRetrospective case series. A case of CDI was defined as (1) Bowel movements >3 or stool output >600 mL WITH, (2) positive laboratory test, either through toxin detection via ELISA prior to 2010 or molecular testing via PCR after 2010.ResultsDuring the study period from 2008 to 2015, 359 patients with RCC or MM receiving IL2 treatment were evaluated with a total of 294 patients undergoing Clostridium difficile testing (CDT). Median age was 52 (range 24–69), 33% female. An average IL2 dose of 27 million international units (MIU) was given in this population. 15% (45/294) had a positive CDT, but 7% (21/294) were found to have CDI. All patients with CDI had antibiotic exposure within the last 30 days of diagnosis. Of the patients who developed CDI, 24% (5/21) had a previous CDI episode within the last 90 days. None of the patients developed megacolon. Developing CDI lead to an all-cause mortality of 24% (5/21).ConclusionThe results of this study show a lower CDI rate (7%, 21/294) than previously reported in IL2-treated patients (66%, 4/6), but this difference is likely due to the difference in population size. In addition to CDI rate, this study adds information about mortality in IL2-treated patients with CDI, which was not previously described in the literature. Applying a clinical criterion to laboratory testing results revealed a difference in laboratory testing positivity and actual infection rates, suggesting 8% of this population maybe colonized with Clostridium difficile, providing further evidence for Antibiotic Stewardship Committees to put in place local guidelines to avoid indiscriminate CDT in this population.Disclosures All authors: No reported disclosures.

2822 Twelve-Month Durability of Microbiota-Based Drug RBX2660 for Preventing Clostridioides difficile Infection (CDI) Is Not Associated With Patient Demographics: Sub-Population Analysis of a Phase 2 Open-Label Study

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) is an urgent public health threat that is associated with significant mortality and substantial medical cost. Microbiota therapy is gaining acceptance to prevent rCDI in multi-recurrent individuals. Two Phase 2 clinical studies have reported the efficacy of RBX2660, a standardized, stabilized microbiota-based drug, in preventing rCDI. To address the suggestion of demographic differences on treatment outcome, we investigated two key demographic stratifications (age and gender) of rCDI subjects enrolled in the Phase 2 open-label study and their associations with outcomes through 12 months post-RBX2660 treatment. METHODS: Data were drawn from a multi-center, open-label Phase 2 study (NCT02589847) in which subjects with multi-recurrent CDI received &lt;2 doses of RBX2660 delivered via enema 7 days apart; this analysis includes data to 12 months after completion of dosing, with ongoing follow-up through 24 months. Efficacy was defined as absence of CDI recurrence through 56 days after the last dose; and durability is defined as a continued lack of reported CDI occurrence. Subjects were censored from subsequent time intervals if they experienced a new CDI occurrence. Fisher’s exact test was performed comparing the proportion of treatment subjects who were recurrence-free by subgroup: age, &gt;65 years vs. &lt;65 years; sex, male vs. female. RESULTS: This study included 149 RBX2660-treated participants in the USA and Canada. Eight-week efficacy for RBX2660 in preventing rCDI (76.5%; 114/149) was higher than CDI-free rates in the historical control group (51.8%, 57/110; P &lt; 0.0001). Of the 114 RBX2660 subjects who achieved treatment success through 8-weeks, 109 subjects had 6-month follow-up data. Of those, three experienced a new CDI episode through 6 months. Between 6 and 12 months, two additional subjects experienced a CDI occurrence. The overall durability through 12 months is 91.7%, as four of the 109 subjects didn’t complete 12-month follow-up and were conservatively assessed as failures. Age and gender did not have a statistically significant impact on efficacy outcome (Table 1). The safety profile through 12 months is consistent with previous reports for RBX2660. CONCLUSION: RBX2660, a microbiota-based drug, was efficacious for preventing rCDI, with clinical durability to at least 12-months after treatment. Importantly, durability was not dependent on age or gender. Twenty-four month follow-up of efficacy and safety are ongoing.

837 Short Chain Fatty Acid Profiles Are Altered by Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection

INTRODUCTION: Recurrent C. difficile infection (rCDI) is a major challenge among patients with inflammatory bowel disease (IBD). Perturbation of microbiota-mediated metabolism of short chain fatty acids (SCFA) has been reported in IBD patients. Fecal microbiota transplantation (FMT), an established therapy for rCDI, alters gut microbiota composition, but effects on SCFA are unclear. Accordingly, this study assessed SCFA profiles in IBD patients with rCDI pre- and post-FMT. METHODS: This open-label, prospective, single-arm multi-center cohort study enrolled patients from 4 tertiary care centers. Patients with IBD and ≥2 episodes of CDI received a single colonoscopic FMT from a universal stool bank. The primary outcome was CDI recurrence up to week 8 defined as diarrhea and EIA-positive toxin testing for C. difficile. Stool for metabolomic profiling was collected pre-FMT and week 1, 8 and 12 weeks post-FMT. A targeted gas chromatography-mass spectrometry protocol was used for the identification and quantification of SCFA. SCFA concentrations were analyzed via univariate analysis, comparing groups (e.g. pre- vs post-FMT). RESULTS: 37 participants were enrolled, with mean age of 37.6 years (range 20-76) and primarily female (n = 21, 57%). 14 had Crohn’s disease (CD) (mean HBI = 6.4) and 23 had ulcerative colitis (UC) (mean Partial Mayo Score = 4.5). Mean baseline fecal calprotectin was 1804.8 +/- 2307.7 Overall, 3 participants (8%) experienced FMT failure with confirmed EIA-positive stool, and the there were no related serious adverse events. Among the nine SCFAs assessed, including two branched chain fatty acids (isovalerate and isobutyrate) most were significant altered by FMT, with rapid and sustained changes (with the exception of acetate, in which no change was appreciated) (Figure 1). Additionally, 2-hydroxybutyrate and lactate, two markers of metabolic stress, were significantly reduced after FMT. Furthermore, the baseline stool samples of those who went on to recur were compared to those who did not (Figure 2); though not significant, there was a trend towards reduced baseline levels for butyrate, propionate and caproate among those who recurred. CONCLUSION: To our knowledge, this is the largest prospective trial to assess the effect of FMT in patients with IBD-CDI. The data suggests the efficacy and safety profile is better than previous reports. SCFAs were increased significantly post-FMT, and may offer insight into mechanism of clinically efficacy seen in this study.

Oral vancomycin prophylaxis during systemic antibiotic exposure to prevent Clostridiodes difficile infection relapses.

To determine whether oral vancomycin prophylaxis accompanying systemic antibiotics reduces the risk of relapse in patients with history of Clostridioides difficile infection (CDI). Retrospective cohort study. Adult inpatients with a history of CDI who received systemic antibiotics in either of 2 hospitals between January 2009 and June 2015. We compared relapse rates in patients who started oral vancomycin concurrently with systemic antibiotics (exposed group) versus those who did not. We assessed for CDI relapse by toxin or nucleic acid testing at 90 days. We used inverse probability weighting and machine learning to adjust for confounders, to estimate propensity for treatment, and to calculate odds ratios for CDI relapse. We performed secondary analyses limited to toxin-positive relapses, patients with 1 versus &gt;1 prior CDI episodes, and patients who received oral vancomycin on each antibiotic day. CDI relapse occurred within 90 days in 19 of 193 exposed patients (9.8%) versus 53 of 567 unexposed patients (9.4%; unadjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.60-1.81; adjusted OR, 0.63; 95% CI, 0.35-1.14). CDI relapses at 90 days were less frequent in exposed patients with only 1 prior episode of CDI (OR, 0.42; 95% CI, 0.19-0.93) but not in those with &gt;1 prior episode (OR, 1.19; 95% CI, 0.42-3.33). Our findings were consistent with a lack of benefit of oral vancomycin when restricting results to toxin-positive relapses and to patients who received vancomycin each antibiotic day. Prophylactic oral vancomycin was not consistently associated with reduced risk of CDI relapse among hospitalized patients receiving systemic antibiotics. However, patients with only 1 prior CDI episode may benefit.

Characterization and risk factors for recurrence of Clostridioides (Clostridium) difficile infection in Japan: A nationwide real-world analysis using a large hospital-based administrative dataset

ObjectiveRecurrent Clostridioides (Clostridium) difficile infection (rCDI) is common and increases healthcare resource utilization. In this study, we assessed rCDI risk factors using an up-to-date, Japanese national hospital-based database. MethodsC. difficile infection (CDI) episodes, occurring July 2014–June 2017, in patients aged ≥18 years were extracted from the database and a nested case-control analysis was performed. Cases were defined as rCDI episodes which required re-initiation of oral vancomycin or oral/intravenous metronidazole treatment within 8 weeks from the start of initial treatment. Cases were matched to 4 non-rCDI episodes at the timing of rCDI occurrence. Adjusted odds ratios (ORs) were estimated using multivariate conditional logistic regression model. ResultsOf 18,246 initial CDI episodes, 3250 (17.8%) had at least one rCDI. Approximately 90% of episodes occurred in inpatients and 65% were treated with metronidazole. Older age (<75 years vs 75–84 years and vs 85 + years) was associated with higher risk of rCDI (OR = 1.27, 95% confidence interval [1.15, 1.41] and 1.45 [1.30, 1.61], respectively). Use of systemic antibiotics (3.16 [2.90, 3.44]), probiotics (2.53 [2.32, 2.77]), chemotherapy (1.28 [1.08, 1.53]), or proton pump inhibitors (PPIs) (1.17 [1.07, 1.28]), and prior CDI history (1.22 [1.03, 1.43]) were also identified as rCDI risk factors. Vancomycin reduced the risk of rCDI compared with metronidazole treatment (0.83 [0.76, 0.91]). ConclusionThis large, multicenter, nationwide study confirmed that older age, PPIs, antibiotics, probiotics, chemotherapy, and prior CDI history are risk factors for rCDI in Japan. There was a 17% decrease of rCDI risk with vancomycin vs metronidazole treatment.Clinical trial registration number: N/A.

Quality of life and utility decrement associated with Clostridium difficile infection in a French hospital setting

BackgroundClostridium difficile infection (CDI) is associated with a substantial Quality of life impact on patients that has not been so far measured with a generic validated instrument.MethodsA prospective study was performed in 7 French acute-care settings in patients presenting with a bacteriologically-confirmed CDI. The EQ-5D-3 L was filled in by patients at 7 ± 2 days after CDI diagnosis to describe their state of health at that date as well as their state of health immediately before the CDI episode (baseline). Individual utility decrement was obtained by subtracting the corresponding utilities. The Quality Adjusted Life Year (QALY) loss was calculated by multiplying the days spent from baseline to the date of the interview, by the decrement of utility. A multivariate analysis of variance of the utility decrement according to CDI and patients characteristics was performed.ResultsEighty patients were enrolled (mean age: 69.4 years, 55% females). The utility scores dropped from a mean 0.542 (SD: 0.391) at baseline to 0.050 (SD: 0.404) during the CDI episode with a mean adjusted utility decrement of 0.492 (SD: 0.398) point. This decrement increased significantly with CDI severity (Zar score ≥ 3) (p = 0.001), in patients with a positive baseline utility (p = 0.032), in women as compared to men (p = 0.041) and in patients aged more than 65 years (p = 0.041). No association with the Charlson index was found. The associated QALY loss not integrating the excess mortality was 0.028 (SD: 0.053).ConclusionsThe impact on quality of life of CDI episodes is major and translates in a substantial QALY loss despite their short duration.

Recurrence of Clostridium difficile infection in the Western Australian population.

Clostridium difficile, the most common cause of hospital-associated diarrhoea in developed countries, presents major public health challenges. The high clinical and economic burden from C. difficile infection (CDI) relates to the high frequency of recurrent infections caused by either the same or different strains of C. difficile. An interval of 8 weeks after index infection is commonly used to classify recurrent CDI episodes. We assessed strains of C. difficile in a sample of patients with recurrent CDI in Western Australia from October 2011 to July 2017. The performance of different intervals between initial and subsequent episodes of CDI was investigated. Of 4612 patients with CDI, 1471 (32%) were identified with recurrence. PCR ribotyping data were available for initial and recurrent episodes for 551 patients. Relapse (recurrence with same ribotype (RT) as index episode) was found in 350 (64%) patients and reinfection (recurrence with new RT) in 201 (36%) patients. Our analysis indicates that 8- and 20-week intervals failed to adequately distinguish reinfection from relapse. In addition, living in a non-metropolitan area modified the effect of age on the risk of relapse. Where molecular epidemiological data are not available, we suggest that applying an 8-week interval to define recurrent CDI requires more consideration.

1950. Prevention of Recurrent Clostridium difficile at Six Months Following Treatment With Microbiota-Based Therapy RBX2660: Durability Results From a Phase 2 Open-Label Study

BackgroundNumerous microbiota-based therapies are being evaluated for prevention of C. difficile infection (rCDI), a public health threat with high recurrence rates associated with the current standard of care. RBX2660, a standardized microbiota-based drug, was efficacious for preventing rCDI in a double-blinded Phase 2b clinical study (PUNCH CD 2). Herein we report the durability of RBX2660 beyond the initial primary clinical end-point of a subsequent Phase 2 open-label study, demonstrating rCDI prevention at 6 months post-treatment.MethodsThis prospective, multi-center, open-label Phase 2 study enrolled subjects who had experienced either ≥2 recurrences of CDI following standard-of-care antibiotic therapy or ≥2 episodes of severe CDI requiring hospitalization. Participants received up to two doses of RBX2660 delivered via enema with doses 7 days apart. The primary endpoint of the open-label clinical study defined efficacy as absence of CDI at 8 weeks from the last dose. Safety follow-ups and durability assessments occurred via telephone at 3, 6, 12, and 24 months. The study is ongoing, and not all subjects have completed their assessments.ResultsThis study included 149 RBX2660-treated subjects and 110 historical control subjects from 31 and 4 centers, respectively, in the United States and Canada. At 8-weeks post-treatment, RBX2660’s efficacy in preventing rCDI (79.9%; 119/149) was higher than CDI-free rates in the historical control group (51.8%, 57/110; P < 0.001). Of the 119 subjects who were determined to be treatment success at 8 weeks, 117 have data through 6 months, of which 8 were exited for non-CDI reasons. Of those 109 subjects through the 6-month follow-up, 3 (2.8%) had a new CDI beyond 8 weeks after enema. The 6-month long-term CDI-free rate was 97.2% (106/109) (median follow-up: 182 days; mean: 177 days).ConclusionRBX2660, a microbiota-based drug, was efficacious for the prevention of recurrent CDI with long-term durability at 6-months post-treatment; a result consistent with 6-month rCDI prevention reported for the Phase 2b PUNCH CD 2 trial. Long-term follow-up of RBX2660 safety and efficacy 24 months is ongoing.This analysis was funded by Rebiotix Inc., Roseville, MN.Disclosures S. Mische, Rebiotix, Inc.: Employee, Salary. R. Orenstein, Rebiotix, Inc.: Scientific Advisor, Consulting fee. E. R. Dubberke, Rebiotix, Inc.: Scientific Advisor, Consulting fee. S. Khanna, Rebiotix, Inc.: Scientific Advisor, Consulting fee and Research support. G. Hecht, Rebiotix, Inc.: Scientific Advisor, Consulting fee. H. Dupont, Rebiotix, Inc.: Investigator, Research support. C. Lee, Rebiotix, Inc.: Scientific Advisor, Consulting fee. K. Blount, Rebiotix, Inc.: Employee, Salary.

1122. Evaluation of Fecal Microbiota Transplant (FMT) in Elderly Patients With recurrent Clostridium difficile Infection (CDI)

BackgroundCDI is a bacterial infection that typically occurs after the use of broad-spectrum antibiotics. Older adults are particularly susceptible to this potentially deadly disease and at higher risk of recurrence.MethodsThe study was approved by the hospital’s IRB. Patients 65 years of age and older with refractory or recurrent CDI who received FMT administered via colonoscopy or oral capsules were included. Patients with severe-complicated infection were excluded and ineligible to receive FMT. Each patient was evaluated 8 weeks post-transplant to assess for sustained clinical response and adverse events. Data collection included patient demographics, number of recurrent CDI episodes, CDI severity, previous antibiotic treatment regimens, clinical cure, adverse events, and donor information.ResultsThirty-five patients were enrolled (23 colonoscopy FMT vs. 13 oral capsule FMT). One patient received FMT via colonoscopy twice. Mean age was 77 years [65–93], female 60%, median recurrent episode was 3, and median CDI severity score was 2. Total success rate was 69.4% (25/36), 60.9% (14/23) via colonoscopy vs. 84.6% (11/13) via capsule. Total success rate for female 67% vs. 73% male and age group of 65–75 was 60% vs. 76% in age group 75+. For capsules only, cure rate was 80% in female vs. 100% in male and 75% in 65–75 age group vs. 89% in patients older than 75 while in colonoscopy only group, success rate was 55% in female vs. 67% in males and 46% in 65–75 age group vs. 67% in age group 75+. There did not seem to be a correlation between FMT donor and success rate. No serious adverse events were reported in the study population.ConclusionFMT may be considered a potentially useful therapy for the treatment of refractory or recurrent CDI cases in patients 65 years of age and older. Further studies are needed to confirm the above findings. Older adults are particularly susceptible to this potentially deadly diseaseDisclosures All authors: No reported disclosures.