Prior Clostridium Difficile Infection Research Articles

686. Management and Outcomes of Patients Referred to a Specialty Clinic for C. difficile Infection

Abstract Background Clostridioides difficile infection (CDI) poses an urgent threat in the United States with an estimated 223,900 cases of hospitalization and 12,800 estimated deaths in 2017. CDI manifestations range from diarrhea, pseudomembranous colitis, to fulminant colitis. Due to spores that are unaffected by current antimicrobial therapies, recurrence remains a common challenge. Patients with 2 or more episodes have an estimated 40-65% rate of recurrence. We reviewed the management and outcomes of patients referred to our specialty CDI clinic. Methods A retrospective chart review was conducted on all new patients presenting to the Loyola University Medical Center CDI clinic between 01/01/2021 and 12/31/2021. Each chart was reviewed for demographic information, comorbidities that may confound diagnosis, and characteristics that place the patient at high risk of recurrent CDI. Visits were characterized by the number of prior CDI episodes, timeline of recurrences, and prior therapies used. 30- and 60-day symptom recurrence were assessed. Results A total of 48 new patients presented to the CDI clinic. The median age was 63 years, 64.5% were white, and 64.5% were female. Patients presenting with recurrent CDI accounted for 79% of cases (38/48), with 48% (13/48) of patients having two or more recurrences. The most common decision for initial management was to not give further antimicrobials and monitor for symptoms (35%). 12% of patients only required monitoring while 23% of patients had a questionable CDI diagnosis and were referred elsewhere for further evaluation. For the 30 patients who received treatment, vancomycin or fidaxomicin tapers were selected 73% (22/30) and bezlotoxumab 20% (6/30) of the time. 8.6% (2/23) of patients with a history of two or more CD episodes had recurrence. Overall, patients experienced a subsequent recurrence rate of 12.5% (6/48) and 15% (7/48) at 30 and 60 days, respectively. The number of times each management approach was selected for initial patient appointments. The number of times each treatment regimen was selected when a patient was deemed to need antibiotic therapy. The percentage of patients who had either recurrence or resolution at 60 days after the end of therapy. Conclusion CDI is a difficult-to-treat infection with many patients suffering from multiple recurrences. Dedicated outpatient follow-up is important for monitoring therapy and excluding alternate etiologies. Expert management of CDI through a dedicated clinic results in lower recurrence for high-risk patients and spared 35% of patients further antimicrobial exposure. Disclosures Larry H. Danziger, PharmD, Ferring Pharmacetuicals: Advisor/Consultant Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria

C. Difficile Infection within 6 Months before TKA Is Associated with Increased Short-Term Complications.

A history of Clostridium difficile infection (CDI) before total knee arthroplasty (TKA) may be a marker for poor patient health and could be used to identify patients with higher risks for complications after TKA. We compared the frequency of 90-day postoperative CDI, complications, readmissions, and associated risk factors in (1) patients experiencing CDIs more than 6 months before TKA, (2) patients experiencing CDIs in the 6 months before TKA, and (3) patients without a history of CDI. We identified patients who underwent primary TKAs from 2010 to 2019 and had a history of CDI before TKA (n = 7,195) using a national, all-payer database. Patients were stratified into two groups: those with CDIs > 6 months before TKA (n = 6,027) and those experiencing CDIs ≤ 6 months before TKA (n = 1,168). These patients were compared with the remaining 1.4 million patients without a history of CDI before TKA. Chi-square and unadjusted odds ratios (ORs) with 95% confidence intervals (CI) were used to compare complication frequencies. Prior CDI during either timespan was associated with higher unadjusted odds for postoperative CDI (CDI > 6 months before TKA: OR 8.03 [95% CI 6.68-9.63]; p < 0.001; CDI ≤ 6 months before TKA: OR 59.05 [95% CI 49.66-70.21]; p < 0.001). Patients with a history of CDI before TKA were associated with higher unadjusted odds for 90-day complications and readmission compared with patients without a history of CDI before TKA. Other comorbidities and health metrics were not found to be associated with postoperative CDI (i.e., age, obesity, smoking, antibiotic use, etc.). CONCLUSION: CDI before TKA was associated with higher odds of postoperative CDI compared with patients without a history of CDI. CDI ≤ 6 months before TKA was associated with the highest odds for postoperative complications and readmissions. Providers should consider delaying TKA after CDI, if possible, to allow for patient recovery and eradication of infection.

The prevalence, risk factors, and complications of Clostridium difficile infection in a tertiary care center, western region, Saudi Arabia

BackgroundClostridium difficile is an anaerobic gram-positive spore-forming bacillus that is most commonly associated with nosocomial diarrhea. This study aimed to analyze the prevalence and risk factors of Clostridium difficile infection (CDI) at a tertiary health care center, Western region, Saudi Arabia. We also aimed to examine the duration of exposure to each risk factor prior CDI development, and to categorize CDI as severe and non-severe depending on the white blood cell (WBC) count. Various complications of the infection were also analyzed. MethodsWe performed a retrospective chart review of all patients who had a positive nucleic acid amplification test (NAAT) for Clostridium difficile toxin genes between October 2018 and October 2020. ResultsThe prevalence of CDI among the included patients was 9.1% (237 of 2611 patients). The mean age (standard deviation) was 56.86 (21) years, and the infection was more prevalent among men (52.74%) than among women (47.26%). The most common risk factor associated with CDI was recent antibiotic use (74.68%), followed by recent acid suppressant use (67.50%), malignancy (46%), and previous gastrointestinal surgery (6.30%). The CDI recurrence rate was 13.90%. Piperacillin-tazobactam was the most frequently used broad-spectrum antibiotic, and was used in 38.8% of the patients, followed by meropenem. The most common malignancy type was lymphoma (22.94%, n = 25), followed by leukemia (n = 23). The most common type of surgery was subtotal colectomy (n = 6). Three patients underwent transverse colon resection, and two underwent ileocecal resection. Hypotension was the most frequently recorded complication (28.40%) in the study population. ConclusionThe prevalence rate of CDI among the study patients during the two-year study from October 2018 to October 2020 was 9.1%. Appropriate use of antibiotic and acid suppressants, and contact isolation measures can help in decreasing the number of CDI cases.

759. Impact of Clostridium difficile (CD) Nucleic Acid Amplification Test (NAAT) Approval on Hospital-Onset C. difficile Infection (HO-CDI): A Diagnostic Stewardship Intervention

BackgroundNAAT is highly sensitive in detecting toxigenic CD but if used inappropriately can lead to overdiagnosis and financial penalties. Despite diligent infection control (IC) measures, HO-CDI rates at our hospital remained above target benchmarks. We implemented mandatory CD testing approval to decrease HO-CDI rates. MethodsOn 7/1/2019, we implemented CD testing approval for stool samples collected after admission day 3 in our 129-bed community hospital. An algorithm instructed providers about approval granted by IC 7 days-a-week. The micro-lab would not process samples unless pre-approved. We prospectively collected data on demographics, ICU, laxative, antibiotic use, CDI signs/symptoms, prior CDI and outcomes (length of stay, in-hospital death) and estimated unadjusted relative risk ratios comparing those whose test was approved vs not approved. We also performed an interrupted time series analysis to assess the trend change of CD testing and HO-CDI per 1000 patient days (x 1000-PD) in the 18 months following the intervention (7/2019 - 12/2020) compared to the pre-intervention period (01/2018 - 6/2019). Lastly, using the National Healthcare Safety Network criteria, we calculated pre and post-intervention Standard Infection Ratios (SIR). ResultsA total of 72 samples required CD testing authorization; 65 (90%) were approved. Baseline demographics, in-hospital death and length of stay were similar in both groups, but approved patients were 4 times as likely to have ≥ 3 loose stools in 24h compared to not approved. The number of CD tests was 13 at baseline with a decrease of 6 tests in the 1st month of intervention (95% CI: -10.0, - 1.35), followed by an insignificant decline in the monthly trend (-0.14; 95%CI: -0.49, 0.20). There were 22 HO-CDI pre-intervention and 10 post-intervention. Pre-intervention, incidence of HO-CDI was 0.51 cases x 1000-PD and increased every month by 0.11 (95% CI: 0.07,0.16). In July 2019, there was a significant decline of 1.16 case x 1000-PD (95% CI: -1.99, -0.33), followed by monthly decline (-0.16; 95% CI: -0.23, -0.09). Our calculated SIR after the intervention decreased to 0.77 from 1.03. Trends of CD testing and HO-CDI in the pre-intervention and post-intervention period ConclusionCD testing approval is a successful strategy to optimize testing and lower HO-CDI rates, without resulting in worst outcomes even when CD test was not approved. Disclosures All Authors: No reported disclosures

19. The Impact of Investigational Purified Microbiome Therapeutic SER-109 on Health-Related Quality of Life (HRQoL) of Patients with Recurrent Clostridioides difficile Infection (rCDI) in ECOSPOR III, a Placebo-Controlled Clinical Trial

BackgroundFollowing standard of care antibiotics, investigational microbiome therapeutic, SER-109, achieved superiority vs placebo (PBO) at 8 weeks in reducing rCDI in patients with ≥3 prior episodes (12.4% vs 39.8%, respectively; p< 0.001). We evaluated the impact of SER-109 vs PBO on HRQoL with general (EQ-5D-5L) and disease-specific (Cdiff32) measures [Garey 2016]. MethodsEQ-5D-5L measures outcomes in 5 domains (mobility, self-care, activities, pain/discomfort, and anxiety/depression) while Cdiff32 measures outcomes in 3 domains (physical, mental, and social) including 5 associated subdomains. Patients completed EQ-5D-5L and Cdiff32 measures at baseline (BL), Wk 8, and at recurrence/early termination. Changes from BL were assessed between SER-109 vs PBO and by clinical outcome (recurrence versus nonrecurrence) in the ITT population and within each treatment arm. The between treatment group comparison analysis controlled for age, gender, prior antibiotics, and number of prior CDI episodes.ResultsMean EQ-5D-5L and Cdiff32 scores were comparable between SER-109 and PBO at BL. EQ-5D-5L did not detect differences at Wk 8 from BL between SER-109 and PBO or by clinical outcome. In contrast, Cdiff32 detected significant improvements at Wk 8 from BL within both SER-109 subjects and PBO subjects (Fig1) and by recurrence status (Fig2). Subjects achieved significant improvement in all domains at Wk 8 from BL regardless of treatment group. When examining recurrence status within treatment arms, all PBO subjects with non-recurrence showed improvement in all health domains, while PBO subjects with recurrence had declines in several subdomains (Fig3B). Similarly, SER-109 subjects with non-recurrence showed improvement in all domains compared to BL. However, overall and mental domain/subdomains scores also improved in SER-109 subjects with recurrence (Fig3A). ConclusionSignificant HRQoL improvements were associated with CDI nonrecurrence, which highlights the negative impact of this debilitating infection. SER-109 was associated with improved overall and mental scores, regardless of clinical outcome. Further investigation is warranted on the impact of SER-109 on mental health even among those with CDI recurrence.Disclosures Elizabeth Hohmann, MD, Seres Therapeutics (Research Grant or Support) Paul Feuerstadt, MD, FACG, Ferring/Rebiotix Pharmaceuticals (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Finch Pharmaceuticals (Scientific Research Study Investigator)Merck and Co (Speaker’s Bureau)SERES Therapeutics (Consultant, Scientific Research Study Investigator)Takeda Pharmaceuticals (Consultant) Christine Lee, MD, FRCPC, Pfizer (Board Member)Rebiotix-Ferring (Board Member)Rebiotix-Ferring (Grant/Research Support)Seres (Grant/Research Support)Summit (Grant/Research Support) Sissi Pham, PharmD, Seres (Consultant) Pat Ray Reese, PhD, Reese Associates, LLC (Consultant, Independent Contractor) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder) Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

Real-World Comparison of Bezlotoxumab to Standard of Care Therapy for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence.

Bezlotoxumab (BEZ) is a monoclonal antibody used to prevent recurrent Clostridioides difficile infection (rCDI). This study investigates BEZ effectiveness in relation to rCDI and patient-specific risk factors in a real-world setting. A matched, retrospective cohort study was conducted from 2015 to 2019 to compare BEZ to historical standard of care (SoC) therapy with vancomycin or fidaxomicin. The primary outcome was incidence of 90-day rCDI. Secondary outcomes were incidence of all-cause hospital readmission and all-cause mortality at 90 days, infusion-related reactions, and incidence of heart failure exacerbation. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). Overall, 107 participants were included (54 BEZ and 53 SoC). Mean number of prior CDI episodes was 2, median number of risk factors for rCDI was 4, and 28% of participants had severe CDI. Incidence of 90-day rCDI was 11% BEZ vs 43% SoC (P = < .001) and 90-day all-cause readmission was 40% BEZ vs 64% SoC (P = .011). In IPTW-adjusted analyses, BEZ was associated with significantly reduced odds of rCDI (odds ratio [OR], 0.14 [95% confidence interval {CI}: .05-.41]) and all-cause readmission (OR, 0.36 [95% CI: .16-.81]). No safety signals were detected with BEZ use. BEZ is effective for the prevention of rCDI and reduction in all-cause hospital readmission for patients at high risk for recurrence, supporting current guideline recommendations.

Toxigenic Clostridium Difficile Colonization in Patients with Hematologic Malignancies Admitted to the Hospital for Chemotherapy or Hematopoietic Cell Transplantation

Background: Clostridium difficile (CD) is an important cause of infectious diarrhea in patients with hematologic malignancies (HM) admitted to the hospital for chemotherapy or hematopoietic cell transplantation (HM-HCT patients). These patients are at increased risk of developing Clostridium difficile infection (CDI) compared to non-oncology patients, and they are more likely to suffer adverse outcomes from the infection. Asymptomatic colonization of patients with CD is known to precede infection. However, the reported prevalence of asymptomatic colonization varies widely between studies. The primary objective of this study was to define the prevalence of toxigenic CD colonization in patients with hematologic malignancies who were admitted to the hospital for scheduled chemotherapy or hematopoietic cell transplantation (HCT). The secondary objective was to determine what microbiology tests are accurate in detecting CD colonization compared to the gold standard of toxigenic culture.Method: We performed a prospective cohort study of HM-HCT patients at our institution. Patients were included if they were age 18 years or older and scheduled for elective admission for chemotherapy or HCT (including both autologous and allogeneic HCT). Patients were excluded if they had diarrhea due to CDI in the past 30 days; if they had diarrhea of unknown etiology; if they were admitted on an unscheduled basis for treatment of acute illness; or if their anticipated length of stay was less than 72 hours. At the time of hospital admission for scheduled chemotherapy or HCT, a stool specimen was collected from each patient in a clean sterile collection vial. All samples were freshly collected and sent to the microbiology laboratory for processing. The stool samples were tested with six different methods: Simplexa™ C. difficile PCR Universal Direct Kit, Cepheid Xpert® PCR C.difficileCD/Epi (Xpert CD/Epi), C. diff Quik Chek Complete® GDH, C. diff Quik Chek Complete® Toxin A/B, LEUKO EZ VUE® ELISA test, and toxigenic culture. Toxigenic culture was used as the reference method. Baseline characteristics of those who tested positive versus negative were described using summary statistics, and univariable logistic regression analysis was used to identify risk factors for CD colonization. Sensitivity and specificity with 95% confidence interval for five tests were estimated.Results: A total of 114 patients were recruited for participation between April 2016 and November 2016. Thirteen patients either withdrew consent or did not provide a stool sample, so the final CD analysis included 101 patients. The demographic and clinical characteristics of the included patients are presented in Table 1. The prevalence of toxigenic CD colonization as determined by toxigenic culture was 13% (14/101, [95% CI: 8-22%]). The Cepheid Xpert PCR CD/Epi showed the highest sensitivity. The sensitivity and specificity of the different testing methods are shown in Table 2. The median (range) length of hospital stay was 13 (2-57) days. Among the 14 patients who tested positive by toxigenic culture, only 1 patient (7%) patient developed CDI during his hospitalization, and his stool tested positive by Cepheid Xpert PCR CD/Epi prior to the development of CDI. Univariable logistic regression analysis did not identify any risk factors for CD colonization including prior CDI, antibiotic use in the past 30 days, or treatment with proton pump inhibitors.Conclusions: Toxigenic CD colonization was high in our cohort of patients, but the majority of patients who were colonized with toxigenic CD did not develop CDI while hospitalized. There were no identifiable risk factors for CD colonization. The most sensitive test for identifying toxigenic CD colonization was the Cepheid Xpert PCR CD/Epi test. Our findings suggest that the Cepheid Xpert PCR CD/Epi test could be used to screen for toxigenic CD colonization in patients admitted for scheduled chemotherapy or HCT. However, the costs and benefits of such an approach warrant further investigation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

791. Evaluation of NSAID Exposure as a Risk Factor for Clostridium difficile infection: A Propensity-Score-Matched Case-Control Study

BackgroundExposure to certain medications, particularly antibiotics and proton pump inhibitors, has been associated with increased risk for Clostridium difficile infection (CDI). Studies have suggested an increased risk for CDI associated with exposure to certain non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a retrospective case-control study to evaluate the risk for CDI associated with NSAID use.MethodsThe population included 1338 patients tested for CDI from February–December 2016 at the University of Michigan. NSAID use within 30 days of CDI testing was determined by chart review. Both scheduled and as-needed NSAID use met the definition for exposure, but aspirin use alone did not. Additional clinical data such as comorbid disease and baseline laboratory parameters were extracted through electronic query. A random forest model imputed missing data. A propensity score for NSAID use was developed via logistic regression and included gender, back pain, baseline serum creatinine, osteoarthritis, rheumatoid arthritis, serum albumin, and use of anticoagulant or antiplatelet medications. Cases were matched 1:1 with C. difficile negative controls by propensity score, with a matching caliper of 0.2 x standard deviation of the logit of the score. The final study population consisted of 1256 cases and their matched controls, however 6 cases could not be matched to controls as none had scores within the matching caliper. Conditional logistic regression was used to compare cases to controls.ResultsNSAID use was similar between the two groups on unadjusted analyses. The adjusted, multivariable model demonstrates that non-aspirin NSAID use is not a significant risk factor for CDI (P =.816), after adjustment for comorbid disease burden, age, and history of prior CDI (Table). Older age and prior CDI were independent risk factors for CDI (Table). Table Study population and modeling results ConclusionIn this retrospective case-control study, non-aspirin NSAID use was not associated with an increased risk of CDI. To our knowledge, this is the first study of NSAID use as a risk factor for CDI that accounted for bias due to treatment assignment using a propensity score. Future studies should account for frequency or chronicity of NSAID use, which may affect the results.DisclosuresKrishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)

90-Day Specific Readmission for Clostridium difficile Infection After Hospitalization With an Inflammatory Bowel Disease Flare: Outcomes and Risk Factors.

Patients with inflammatory bowel disease (IBD) have an increased risk for Clostridium difficile infection (CDI) and carry significantly higher morbidities and mortality than those without IBD. We aimed to investigate disease-specific readmission rates and independent risk factors for CDI within 90 days of an index hospitalization for an IBD flare. The Nationwide Readmission Database was queried for the year 2016. We collected data on hospital readmissions of 50,799 adults who were hospitalized for urgent IBD flare and discharged. The primary outcome was disease-specific readmission rate for CDI within 90 days of discharge. The secondary outcomes were readmission rate of colonoscopic procedures, morbidities (including mechanical ventilation and shock), and hospital economic burden. The risk factors for readmission were identified using Cox regression analysis. The 90-day specific readmission rate was 0.1% (N = 477). A total of 3,005 days were associated with readmission, and the total health care in-hospital economic burden of readmission was $19.1 million (in charges) and $4.79 million (in costs). Independent predictors during index admission for readmission were mechanical ventilation for >24 hours (hazard ratio [HR], 6.62, 95% confidence interval [CI], 0.80-54.57); history of previous CDI (HR, 5.48; 95% CI, 3.66-8.19); HIV-positive status (HR, 4.60; 95% CI, 1.03-20.50); alcohol abuse disorders (HR, 2.06; 95% CI, 1.15-3.70); Parkinson's disease (HR, 4.68; 95% CI, 1.65-13.31); index admission for noncomplicated ulcerative colitis (HR, 4.72; 95% CI, 2.99-7.45]-), complicated ulcerative colitis (HR, 4.49; 95% CI, 2.80- 7.18), or noncomplicated Crohn disease (HR, 2.54; 95% CI, 2.80-4.04); and hospital length of stay (HR, 1.01; 95% CI, 1.01-1.02). The 90-day CDI-specific readmission rate after the index admission of IBD flares was 0.1%. We found risk factors for CDI-associated readmissions such as history of Parkinson's disease, prior CDI, HIV-positive status, and alcohol abuse disorder. Finally, our study also revealed a high health care cost, charges, and burden.

Efficacy of Bezlotoxumab in Participants Receiving Metronidazole, Vancomycin, or Fidaxomicin for Treatment of Clostridioides (Clostridium) difficile Infection.

BackgroundIn phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of Clostridioides (Clostridium) difficile infection (rCDI) over 12 weeks. Choice of CDI antibacterial treatment may affect CDI-related outcomes; therefore, this prespecified analysis assessed if the magnitude of bezlotoxumab-induced rCDI reduction was influenced by the antibiotic administered.MethodsIn MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups.ResultsOf 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and fidaxomicin (55.4% and 89.3%, respectively). ICC rates were similar in the bezlotoxumab (metronidazole, 81.0%; vancomycin, 78.5%; fidaxomicin, 86.7%) and placebo groups (metronidazole, 81.3%; vancomycin, 79.6%; fidaxomicin, 76.9%). In placebo-treated participants, the rCDI was lower in the metronidazole subgroup vs the vancomycin and fidaxomicin subgroups (metronidazole, 28.0%; vancomycin, 38.4%; fidaxomicin, 35.0%). When analyzed by subsets based on history of CDI, rCDI rates were similar in the metronidazole and vancomycin groups. rCDI rates were lower in all antibiotic subgroups for bezlotoxumab vs placebo (metronidazole: rate difference [RD], –9.7%; 95% confidence interval [CI], –16.4% to –3.1%; vancomycin: RD, –15.4%; 95% CI, –22.7% to –8.0%; fidaxomicin: RD, –11.9%; 95% CI, –38.1% to 14.3%).ConclusionBezlotoxumab reduces rCDI vs placebo in participants receiving metronidazole and vancomycin, with a similar effect size in participants receiving fidaxomicin.

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.

Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients. We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results. We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified. Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

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.

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.

2365. Volatile Metabolite-Based Detection of Clostridium difficile Infection (CDI)

BackgroundCDI is a frequent cause of morbidity and mortality in hospitalized patients. Despite advances in rapid CDI testing, there are often delays between the onset of symptoms and receipt of test results. We sought to test the hypothesis that the altered CDI intestinal microbiome has a unique volatile metabolite profile, distinct from the profile of patients with other causes of antibiotic-associated diarrhea, which potentially can be used to identify patients with CDI.MethodsWe prospectively collected fresh stool samples from inpatients with suspected CDI at an academic tertiary care hospital from July 2015 to November 2017, adsorbed volatile metabolites from each sample onto sorbent tubes within an hour of sample collection, and used thermal desorption-gas chromatography/tandem mass spectrometry to identify each metabolite. All patients were exposed to at least one antibiotic agent in the prior 90 days, and only patients receiving empiric CDI treatment or with formed stool samples were excluded. We used logistic regression models, adjusting for prior anti-anaerobic antibiotic therapy and CDI severity (serum albumin <3 g/dL and WBC ≥ 15,000/mm3 or abdominal tenderness) and adjusting for multiple testing using Storey’s q-value procedure (with a threshold of q ≤ 0.05), to examine the relationship between CDI, as determined by the reference standard of the cell culture cytotoxicity neutralization assay, and each metabolite.ResultsIn our 565-patient cohort, median age was 61 years (IQR 50, 70) and 277 (49%) were male; 173 (31%) had abdominal pain in the 24 hours before testing, 59 (10%) had fevers in the prior 24 hours, 22 (4%) had an ileus, 74 (13%) had mental status changes in the prior 24 hours, 89 (16%) were hospitalized in the ICU at the time of testing, 45 (7%) were receiving pressors, 82 (15%) had a WBC ≥ 15,000/mm3, and 137 (24%) had a serum lactate > 1.5 mmol/L. Ultimately, 155 patients were diagnosed with CDI. Ten metabolites (Table 1, Figure 1) were differentially distributed in patients with and without CDI.ConclusionWe identified a suite of volatile metabolites that differentiates stool from patients with and without CDI; this profile may ultimately be used to identify patients with CDI. 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.

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.

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection: EXTEND study subgroup analyses

Poor outcomes following Clostridium difficile infection (CDI) have been associated with advanced age, presence of cancer and C. difficile PCR-ribotype 027. The impact of baseline risk factors on clinical outcomes was evaluated using data from the EXTEND study, in which rate of sustained clinical cure (SCC) in the overall population was significantly higher with an extended-pulsed fidaxomicin (EPFX) regimen than with vancomycin. Patients aged ≥ 60 years received EPFX (fidaxomicin 200 mg twice daily, days 1–5; once daily on alternate days, days 7–25) or vancomycin (125 mg four times daily, days 1–10). We analysed outcomes by advanced age, cancer diagnosis, CDI severity, prior CDI occurrence and infection with PCR-ribotype 027. The primary endpoint was SCC 30 days after end of treatment (EOT; clinical response at test-of-cure with no subsequent recurrence). SCC rates 30 days after EOT did not differ significantly between EPFX (124/177, 70.1%) and vancomycin (106/179, 59.2%) regardless of age, cancer diagnosis, CDI severity and prior CDI. In patients with PCR-ribotype 027, SCC rate 30 days after EOT was significantly higher with EPFX (20/25, 80%) than with vancomycin (9/22, 40.9%) (treatment difference, 39.1%; 95% CI, 13.2–64.9; P = 0.006). Subgroup analyses from the EXTEND study suggest that EPFX is efficacious as a potential treatment for CDI regardless of age, cancer diagnosis, infection with PCR-ribotype 027, CDI severity or prior CDI. ClinicalTrials.gov identifier: NCT02254967.

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials.

BackgroundPatients with recurrent Clostridium difficile infection (rCDI) are more likely to have a hospital readmission and spend increased time in inpatient settings compared with patients with primary CDI. MODIFY I and II demonstrated that bezlotoxumab significantly reduced rCDI vs placebo. A post hoc within-trial analysis assessed whether bezlotoxumab was associated with a reduction in cumulative inpatient-days.MethodsData were pooled from the MODIFY trials to estimate the cumulative hospitalized days summed over the 84-day follow-up period. We adjusted inpatient use data from pooled MODIFY I and II for survival and censoring to estimate 84-day cumulative inpatient-days, overall and for subgroups. Treatment effects were obtained using recycled predictions based on trial protocol and rCDI risk, and 95% confidence intervals were obtained using 1000 bootstrap replicates.ResultsMean cumulative inpatient-days were greater in the placebo arm (14.1 days) vs the bezlotoxumab arm (12.1 days) in the overall population. The mean difference between treatment groups was 2.1 days (95% confidence interval, –0.4 to –3.7). This was consistent in participants with risk factors for rCDI: age ≥65 years, compromised immunity, severe CDI, prior CDI, and ribotype 027/078/244 infection. As the number of risk factors increased, bezlotoxumab resulted in greater reductions in the number of inpatient-days compared with placebo (difference: –1.2 days, –2.3 days, –2.5 days, and –3.0 days for 0, 1, 2, and ≥3 risk factors, respectively).ConclusionsBezlotoxumab was associated with a reduction in cumulative inpatient-days, suggesting that treatment with bezlotoxumab may substantially reduce rCDI-associated health care resource use. Trial registrations. MODIFY I (MK-3415A-001, NCT01241552) and II (MK-3415A-002, NCT01513239)

The Effect of Clostridium difficile Infection on Pregnancy and Neonatal Outcomes: An Observational Study

Introduction: There are limited data on Clostridium difficile infection (CDI) in pregnancy.We did a retrospective study to identify the risk factors and management of CDI in pregnant women and assess the effect of CDI on pregnancy and neonatal outcomes. Methods: Cases were identified using diagnostic codes and confirmed by manual chart review. Cases with CDI within 12 weeks prior to pregnancy, throughout pregnancy, or during 6 weeks postpartum were included. Descriptive statistics were performed to evaluate outcomes. Results: Overall, 31 patients [median age 29 (IQR 26-32) years] were included. Commonest risk factors were outpatient or emergency room visit (90.0%) and antibiotic use (51.6%). Two patients had prior CDI. 22.6% (7) had CDI pre-pregnancy; 16.1% (5) in 1st trimester; 29% (9) in 2nd trimester; 19.3% (6) in 3rd trimester and 12.9% (4) postpartum. 67.7% (21) received metronidazole (MET) initially [4 pre-pregnancy, 15 while pregnant (3 in 1st, 7 in 2nd, 5 in 3rd trimester), 2 postpartum], 29.0% (9) vancomycin (VAN) standard regimen, and 3.2% (1) VAN taper. Treatment response data was available in 30; 14 needed change in treatment (11 were on MET, 2 on VAN, 1 on VAN taper): due to non-resolution of symptoms in 11, adverse events (AEs) in 3. Among those with AEs, 2 on MET switched to VAN, 1 on VAN switched to MET. Subsequent treatment for the rest: MET (2), VAN standard regimen (6), combination of both (1), VAN taper (1), fecal microbiota transplantation (FMT) (1). Overall, 23.3% (7/30) had adverse events (AEs); due to MET in 6, VAN in 4 (Figure 1). 6.8% (2/29) had treatment failure; 1 had FMT after fidaxomicin, 1 had colectomy. Two patients had complications from CDI [shock, sepsis, and colectomy (1); shock (1)]. 20.7% (6/29) had CDI recurrence; median 2 episodes (range 1-3).214_A Figure 1. Adverse events (AEs) experiencedDelivery outcomes were available in 26; 15.4% (4) aborted (3 with CDI preceding event, all treated with MET), 84.6% (22) had live births [59.0% vaginal; 40.9% cesarean]. Excluding post-partum CDI (4), 22.7% births were preterm, 9.0% post-term; 88.5% (23/26) had complications in pregnancy (Figure 2). Among neonates, 10.5% (2/19) were low birth weight; 10.5% (2/19) had macrosomia, 50% (7/14) had complications (3 respiratory distress; 4 hypoglycemia; 5 neonatal jaundice; 2 intrauterine growth restriction; 2 fever). None had AEs due to CDI treatment in mother.214_B Figure 2. Complications and outcomes in pregnancy, puerperium, and neonatal periodConclusion: Pregnant women with CDI have high rates of treatment failure and AEs, and higher rates of adverse outcomes when compared with national data.