History Of Clostridium Difficile Infection Research Articles

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.

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)

Anti-toxin antibody is not associated with recurrent Clostridium difficile infection

Clostridium difficile infection (CDI) recurs in ∼20% of patients. Prior studies indicated that antibody responses directed against the C. difficile toxins A and B were potentially associated with lower risk of recurrent CDI. Here we tested the hypothesis that circulating anti-toxin IgG antibody levels associate with reduced risk of recurrent CDI. A cohort study with prospective enrollment and retrospective data abstraction examined antibody levels in 275 adult patients at the University of Michigan with CDI. We developed an enzyme linked immunosorbent assay to detect IgG antibodies against toxin A and toxin B in sera obtained at the time of diagnosis. Logistic regression examined the relationship between antibody levels and recurrence, and sensitivity tests evaluated for follow-up and survivor biases, history of CDI, and PCR ribotype. Follow-up data were available for 174 subjects, of whom 36 (20.7%) had recurrence. Comparing antibody levels vs. recurrence and CDI history, anti-toxin A levels were similar, while anti-toxin B levels had a greater range of values. In unadjusted analysis, detection of anti-toxin A antibodies, but not anti-toxin B antibodies, associated with an increased risk of recurrence (OR 2.71 [1.06, 8.37], P = .053). Adjusting for confounders weakened this association. The results were the same in sensitivity analyses. We observed a borderline increased risk of recurrence in patients positive for anti-toxin A antibodies, and sensitivity analyses showed this was not simply a reflection of prior exposure status. Future studies are needed to assess how neutralizing antibody or levels after treatment associate with recurrence.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. We performed a population-based cohort study using Swedish national register data. Adults aged ≥35years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. Amongst the study population (N=4670423), 34868 (0.75%) had a history of CDI. A total of 165 and 47035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.

Perception of quality of life in people experiencing or having experienced a Clostridioides difficile infection: a US population survey

BackgroundAlthough the incidence, severity and mortality of Clostridioides (Clostridium) difficile infection (CDI) have been increasing, patients’ quality of life changes resulting from CDI have not been studied thoroughly. This study aimed at exploring the consequences of CDI on quality of life through patients’ perspective.MethodsAn observational, cross-sectional study involving 350 participants with a self-reported CDI diagnosis was conducted through an online self-administered survey. Participants were grouped into those who had active disease (“Current CDI”) and those who had a history of CDI (“Past CDI”).ResultsOne hundred fifteen participants (33%) reported Current CDI and 235 (67%) reported Past CDI. A large majority of participants admitted that their daily activities were impacted by the infection (93.9% and 64.7% of Current and Past CDI respondents respectively, p < 0.05). Physical and psychological consequences of CDI were experienced by 63.5% and 66.1% of participants with active CDI. Despite the infection being cleared, these consequences were still frequently experienced in Past CDI cohort with similar rates (reported by 73.2% of respondents for both, physical consequences p = 0.08; psychological consequences p = 0.21). After the infection, 56.6% of respondents noted that post-CDI symptoms remained; 40.9% believed they would never get rid of them.ConclusionsWhile the societal burden of CDI is well described in the literature, our study is one of the first aimed at understanding the major burden of CDI on quality of life. Our results highlight the long-lasting nature of CDI and further reinforce the need for enhanced therapeutics in the prevention and treatment of this devastating infection.

Association of Household Pets, Common Dietary Factors, and Lifestyle Factors with Clostridium difficile Infection.

Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections and is associated with significant morbidity and mortality. Since owning a cat or dog could enrich the gut microbiome, we hypothesized that it would be protective against CDI. We conducted a survey study on patients tested for CDI in order to assess whether living in the presence of a pet is associated with a decreased risk of CDI. We surveyed subjects aged 18-90 over a 14-month period using a retrospective case-control design. Subjects with CDI were matched by gender and age to patients who tested negative and had no prior history of CDI. A web-based survey was provided to subjects by mail or assisted by phone. Conditional logistic regression was used to assess for associations between CDI and the various risk factors. 205 CDI positive and 205 CDI negative subjects (response rate of 50.2%) were included. After matching for age and sex, living with a cat or dog was not associated with negative CDI testing. Exploratory multivariable modeling identified an unexpected association between positive CDI testing and high meat intake (OR 2.13, 95% CI 1.21-3.77) as well as between positive CDI testing and cat allergies (OR 1.88, 95% CI 1.02-3.46). Living with a cat or dog was not associated with negative CDI testing. Several novel risk factors for CDI have been identified including high meat intake and cat allergies.

Enteral Vancomycin Is Effective Clostridium Difficile prophylaxis in Pediatric, Adolescent, and Young Adult Hematopoietic Stem Cell Transplant Recipients

Background Clostridium difficile infection (CDI) is a major source of morbidity for patients undergoing autologous and allogeneic hematopoietic stem cell transplantation (HSCT). CDI can complicate gastrointestinal mucositis, lead to mucosal barrier infections or sepsis, and compromise nutrition after HSCT. CDI may contribute to acute gastrointestinal graft-versus-host disease (GI aGVHD) and reduce overall survival in allogeneic HSCT patients. Use of enteral vancomycin as CDI prophylaxis may reduce morbidity and improve outcomes in HSCT recipients. Methods As a quality improvement initiative, enteral vancomycin was instituted as CDI prophylaxis in all autologous and allogeneic HSCT recipients at Methodist Children's Hospital beginning 02/13/19. Patients were prescribed vancomycin 125 mg oral/enteral twice daily (Ganetsky et al. Clin Infect Disease 2019; 68 (12):2003-2009) from HSCT admission to discharge home. Patients readmitted during the first 100 days after HSCT resumed enteral vancomycin while hospitalized. Physicians, advanced practice providers, and pharmacists monitored enteral vancomycin administration. The infectious disease and prevention team monitored CDI and weekly vancomycin resistant enterococcus (VRE) stool testing per institutional policy. Pre- and post-implementation data was retrospectively reviewed (number of HSCT patients, CDI, VRE, adverse events of enteral vancomycin, and GI aGVHD). Two-sided Fisher's exact test was used to compare CDI before and after institution of enteral vancomycin prophylaxis. Results Between 01/05/2018 and 02/12/2019, the rate of CDI was 29% (n=9/31). After implementation of CDI prophylaxis (02/13/19 to 09/16/19), the rate of CDI was 0% (n=0/23). Enteral vancomycin resulted in a significant reduction in the number of CDI cases (p=0.0068). Prior to implementation of CDI prophylaxis, 26% (n=7/27) of allogeneic HSCT recipients developed GI aGVHD. Of the 7 patients that developed GI aGVHD, 6 had a history of CDI. After implementation of CDI prophylaxis, 7% (n=1/14) of allogeneic HSCT recipients developed GI aGVHD. There were no VRE positive screens or infections. There were no adverse events related to enteral vancomycin. Conclusions Enteral vancomycin appears to be safe and effective CDI prophylaxis in pediatric, adolescent, and young adult HSCT recipients. Since institution of enteral vancomycin prophylaxis, there has been a significant reduction of CDI in our HSCT patients. This quality improvement project is ongoing and future analyses will compare GI aGVHD and overall survival with CDI pre- and post-implementation of enteral vancomycin prophylaxis.

2413. Assessment of compliance with Clostridioides difficile prophylaxis guideline and its efficacy on secondary prophylaxis and reducing hospital-onset Clostridioides difficile infections.

BackgroundOne of the complications of Clostridium difficile infection (CDI) is the risk of recurrence, particularly in high-risk patients who are exposed to broad-spectrum antibiotics (BSA). Antimicrobial stewardship program at our institution developed Clostridium difficile prophylaxis (CDP) guidelines. Purpose of this study was to evaluate the compliance to this guideline and evaluate the efficacy of it preventing recurrent CDI.MethodsThis was an IRB approved retrospective study performed at a 607-bed community health system between 2014–2016. Patients were included if they were ≥18 years old and admitted for > 24 hours on BSA with history of CDI in last 6 months. CDI prophylaxis was provided with oral vancomycin 125 PO BID. Patients were excluded if they had active CDI receiving metronidazole or treatment doses of oral vancomycin. Patients were compared in two cohorts: Study group which was patients in CDP group which were matched to control group. The primary objective of the study was to evaluate the compliance of CDP guidelines and incidence of hospital-onset CDI (HO-CDI) between CDP group and control group. The secondary objective focused on all-cause inpatient mortality and 30-day readmission between two groups.ResultsThere were total of 72 patients reviewed and 47 patients met the inclusion criteria for CDP group which were matched with control group. Most common type of infection and BSA were pnuemonia (26%) and broad-spectrum cephalosporins (31%), respectively. CDP guidelines compliance was measured at 65%. The incidence of HO-CDI/10000 patient-days during the admission was lower in CDP group compared with control group (2.02 vs 5.4 per 10,000 PD, P = 0.03). No differences were seen in all-cause inpatient mortality and 30-day readmission between two groups. Forty-five percent of patients suffered from CDI < 3 months prior to admission. The most common dose of oral vancomycin was 125 mg PO BID.ConclusionPatients in CDP group had a lower incidence of developing HO-CDI compared with control group. Overall compliance with CDP guidelines was higher than expected. No difference was seen in all-cause inpatient mortality and 30-day readmission between two groups. Oral vancomycin 125 mg PO BID shows promising results as a secondary prophylaxis in patients receiving BSA.Disclosures All authors: No reported disclosures.

3054 Getting to the Bottom of Incessant Diarrhea

INTRODUCTION: Clostridium difficile infection (CDI) is a common cause of recurrent diarrhea. Up to 35% of patients experience recurrent infection after initial therapy. Patients with recurrent CDI are occasionally treated empirically with antibiotics. There has been an increase in recurrence in CDI over recent years. In fact, there is a 50-60% chance of a repeat recurrence. Persistent diarrhea is also caused by microscopic colitis, which occurs 7.9 per 100,000 person years. It has been associated with the use of NSAIDs and proton-pump inhibitors (PPI). We present a case of a patient with recurrent CDI who was eventually diagnosed with microscopic colitis. CASE DESCRIPTION/METHODS: A 41-year-old male with a history for DM type 1, renal failure, GERD presented with persistent diarrhea for the past 5 years. His temperature was 98.3 F, HR 87 bpm, BP 123/89 mmHg, and RR was 20 per minute. Physical exam was unremarkable. Laboratory studies were insignificant. CT with contrast was negative for any pathologies. Initial stool testing was negative for CDI. A colonoscopy with biopsy was performed which showed no abnormal findings. He was treated with IV fluids and loperamide. His symptoms persisted and repeat stool was positive for Clostridium difficile toxin. According to guidelines at the time of presentation, he was started on metronidazole and his PPI was discontinued. His symptoms resolved over 48-72 hours and he was discharged. Two weeks later, he presented again with CDI and was treated with oral vancomycin and discharged. He presented with diarrhea 2 months later and was treated empirically with metronidazole, showing minimal to no improvement of his symptoms. Stool studies were negative for Clostridium difficile toxin. A repeat colonoscopy with biopsy showed lymphocytic infiltrates within the colonic mucosa, confirming the diagnosis of lymphocytic microscopic colitis. He was started on budesonide with a good clinical response and was discharged. Follow-up at our clinic showed near-resolution of his symptoms. DISCUSSION: Recurrent diarrhea is a bothersome symptom. Our patient's microscopic colitis was overshadowed by his history of CDI. He was treated empirically for CDI, exposing him to antibiotics and delaying appropriate treatment. Antibiotics may create iatrogenic consequences such as antibiotic resistance. Clinicians must be aware that patients with history of recurrent CDI may have other underlying etiologies for persistent diarrhea.

708 History of Clostridium difficile Infection Predicts Late Colectomy in Patients With Acute Ulcerative Colitis

INTRODUCTION: Studies have identified a significant prevalence of enteric pathogens (EP), most prominently clostridium difficile (CD), in patients with Ulcerative Colitis (UC). The clinical role of these EPs remains debatable, as in patients with UC they often can represent the sole reason for acute presentation, asymptomatic carrier status, or a comorbid presentation with UC. We aimed to study the prevalence of testable EPs in hospitalized UC patients and assess the impact of these pathogens on colectomy outcomes. METHODS: We designed a retrospective study including patients &gt;18 years old with an admission for UC at a single academic center between 1/1/2013 and 4/1/2018. Cases were identified using the ICD-9 code 556.X and ICD-10 code K51.X and separately verified. Clinical variables of interest and laboratory values were obtained via chart review or extracted from the electronic medical record. Logistic regression was performed in order to identify predictors of in-hospital and 90 day colectomy. Statistical analysis was conducted using JMP ® 13.1.0. RESULTS: 262 patients admitted with UC were reviewed. Our study identified 48/251 (19.1%) patients with positive CD testing. 11/91 (12.1%) patients had Non-CD EPs and only 1/91 (1.1%) patient was positive in both tests. The identified infections are outlined in Table 1. We also identified 31/261 (11.9%) who had a positive CD test in 8 weeks prior to admission. Basic demographic and clinical variables are listed in Table 2. History of CD infection in the past 8 weeks before admission predicted Colectomy at 90 days in univariate analysis (P-value = 0.0015). Multivariate logistic regression model with all covariates in Table 2 (excluding non-CD EP status and in-hospital CD infection status) revealed an area under curve = 0.80. History of CD infection in the past 8 weeks remained the only significant predictor within this model of late colectomy at 90 days (P-value = 0.0063, OR = 10.53, 95% CI 1.95-57.0). CONCLUSION: Prior to admission diagnosis of CD infection is a strong predictor of late colectomy at 90 days in hospitalized patients with UC. Multiple explanations are possible including outpatient management of CD delaying initiation of inpatient management of acute UC flares. Conversely, accumulated adverse effects of gut dysbiosis from EPs may occur over weeks before leading to adverse outcomes. Future work is needed to optimally characterize the pathogenicity of both CD and non-CD EPs in UC patients via current testing and treatment strategies.

2600 A Typical Presentation of a Rare Disease: Clostridium difficile Enteritis After Total Abdominal Colectomy

INTRODUCTION: Clostridium difficile enteritis (CDE) is rare, but is increasingly diagnosed among those who have undergone colectomy. After colectomy, colonic-type bacterial flora including Clostridium difficile are able to colonize, and under the right circumstances, infect the small bowel. The reported mortality of CDE is high, likely due in part to the emergence of a virulent strain of Clostridium difficile, NAP1/BI/027. Physicians should have a high index of suspicion for CDE, particularly among patients with antibiotic exposure after colectomy. CASE DESCRIPTION/METHODS: A 50-year-old-woman with a previous history of Clostridium difficile infection (CDI) and colonic inertia status post total abdominal colectomy with ileorectal anastomosis three months prior presented with waves of left lower quadrant abdominal pain, abdominal distention, nausea, and vomiting. In the three weeks prior to admission, she completed courses of Amoxicillin and Trimethoprim-sulfamethoxazole for UTI. CT abdomen/pelvis with contrast showed 20 cm of circumferential thickening of the distal small bowel with associated free fluid and mesenteric inflammation proximal to unaffected ileorectal anastomosis. Laboratory evaluation was notable only for mild leukocytosis (12,000 cells/µL) with no bands. On admission, the patient had a nasogastric (NG) tube placed for abdominal decompression. A Bisacodyl suppository was prescribed, and the patient had a bowel movement that resulted positive for Clostridium difficile toxin DNA PCR. The patient was diagnosed with CDE. She was initially started on NG Vancomycin 150 mg every 6 hours for a first recurrence of CDI, which was then escalated to 500 mg every 6 hours with the addition of IV Metronidazole. This resulted in resolution of symptoms and ileus. DISCUSSION: Our patient had several CDE risk factors including a prior history of colectomy and recent antibiotic exposure. In addition to CDE risk factors, our patient also had two CDI risk factors - chronic acid suppression and previous history of CDI. Additional research is needed to determine if other typical CDI risk factors also play a role in the development of CDE. In patients with altered gastrointestinal anatomy or obstruction, it may be challenging to confirm the diagnosis using stool-based PCR toxin studies. Abdominal CT scan may be helpful in making the diagnosis. Much like our patient, previous studies have demonstrated circumferential edema and mesenteric stranding of the small bowel as common radiologic features of CDE.

1002 Clostridioides difficile Infection in Liver Transplant Recipients

INTRODUCTION: Clostridium Difficile Infection (CDI) has been increasing in prevalence within the United States. The CDC estimates that approximately half a million people are infected every year. Patients with liver transplantation tend to require more hospitalizations with increased frequency of antibiotics and higher risk for CDI. We sought to evaluate outcomes of patients with liver transplantation developing CDI. METHODS: The study population was derived from the HCUP-National Inpatient Sampling (NIS) database for the years 2010 to the third quarter of 2015. ICD-9 codes were used to identify patients with history of liver transplant and CDI. In-hospital all-cause mortality, total cost of hospitalization, mean length of stay and outcomes rates were assessed. Propensity score matching was used to adjust for baseline confounders. RESULTS: A total of 8,567 individuals had a history of liver transplantation and co-existing CDI. Age and race were similar between the two groups; 43.7% of the CDI cohort were female. Patient’s in the control group had higher baseline clinical risk (Table 1). All-cause mortality (3.2% vs 1.7%, P &lt; 0.0001), length of stay (10.4 ± 15.4 vs 5.5 ± 7.4, P &lt; 0.0001), cost of hospitalization ($88,866 ± 166,834 vs $50,724 ± 94,482, P &lt; 0.0001) and blood transfusion rates (13.6% vs 19%, P &lt; 0.001) were higher in the CDI and liver transplant population. Colonoscopy and bowel resection were also performed significantly more frequently in the CDI and liver transplantation cohort (7.1% vs 2.9%, P &lt; 0.0001 and 0.8% vs 1.1%, P = 0.012, respectively) (Table 2). After propensity score matching analysis, these statistically significant differences remained; bowel resection rates were similar between the two groups (1.3% vs 1.1%, P = 0.324). (Table 3). CONCLUSION: CDI in liver transplant recipients is associated with significantly higher rates of in-hospital mortality, blood transfusions, length of stay and total cost of hospitalization. Colonoscopy is used more frequently in the management of this population.

135 Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Patients Above 75 Years of Age: A Tertiary Center Experience

INTRODUCTION: Fecal microbiota transplantation (FMT) is established as an effective treatment for recurrent Clostridioides (formerly Clostridium) difficile infection (CDI). Incidence and mortality from CDI are significantly higher in the elderly population (CDI is 10 times more common and 92% of CDI-related deaths occur in the elderly). Risk of cardiopulmonary complications from sedation prior to colonoscopy is increased in the elderly. Efficacy and safety of FMT via colonoscopy in the elderly are unknown. METHODS: A retrospective study comparing patients ≥75 years, and patients &lt; 75 years who had FMT at Sanford Medical Center, Sioux Falls, SD, between 2013–2018. All patients underwent FMT via colonoscopy. Antibiotics prior to FMT, donor screening, preparation and delivery of FMT, and post-procedural follow up were based on a standardized protocol in our institution. Data on baseline characteristics, co-morbidities, antibiotics-associated with CDI, safety, and success rate of treatment (defined by resolution of symptoms and absence of CDI recurrence at 8 and 52 weeks) were collected. RESULTS: Of 59 patients, 17 (28.8%) were ≥75 years with a mean age of 84.4 years, and 42 (71.2%) were &lt;75 years and a mean age of 46.4 years. Baseline characteristics of both groups are described in Table 1. Number of CDI before FMT, history of severe CDI, nosocomial CDI were similar. No fulminant CDI was reported in our study. In ≥75 years vs. &lt;75 years, serum albumin was lower (3.4 vs 4 g/dl, P &lt; 0.002) and hypertension was more common (52.9 vs 23.8%, P = 0.03). 80% of our study population had a history of antibiotics exposure prior to CDI, but there was no statistically significant difference between groups. Of antibiotics-associated with CDI, penicillins were more likely to be reported in ≥75 vs. &lt;75 years (38.1 vs 5.9%, P = 0.014). Cephalosporins, macrolides, fluoroquinolones, and clindamycin were similar in both groups. Prior to FMT, both groups were treated similarly with vancomycin with or without taper, oral or intravenous metronidazole, or fidaxomicin. No major complications related to anesthesia or FMT via colonoscopy or deaths attributed to FMT were reported in our study. The success rates at 8 and 52 weeks in both groups were similar (76.5 vs. 83.3%, and 76.5 vs. 71.4%, respectively). CONCLUSION: Despite the increased risk of CDI and colonoscopy in the elderly population, success rate and safety of FMT appears to be equivalent between elderly and non-elderly. Prospective studies with larger sample size are needed.

Long-Term Efficacy of Oral Vancomycin Prophylaxis for the Prevention of Clostridium difficile Recurrence

Background: Limited evidence suggests that prophylactic oral vancomycin may be beneficial in preventing Clostridium difficile infection (CDI) recurrence, but long-term efficacy is unknown. Objective: To evaluate the long-term efficacy of oral vancomycin prophylaxis (OVP) in preventing CDI recurrence in subjects who require subsequent antibiotic exposure. Methods: A retrospective cohort study was conducted at a community hospital. A total of 91 subjects with a history of CDI between January 2013 and December 2015 who had a subsequent hospitalization requiring systemic antibiotics within 12 months were evaluated. Thirty-two subjects who received prophylaxis with oral vancomycin were compared to 59 subjects who did not receive prophylaxis. Results: CDI recurrence within 12 months was significantly lower in subjects receiving OVP compared to those who did not receive OVP (6.3% vs 28.8%; odds ratio [OR]: 0.16; 95% confidence interval [CI]: 0.04-0.77; P = .011) including patients whose previous CDI was an initial episode (3.7% [1/27] vs 28.3% [15/53]; OR: 10.3; 95% CI: 1.28-82.6; P = .009). Conclusion: Use of OVP in subjects with a history of CDI up to 12 months prior to subsequent antibiotic exposure appears to reduce the risk of CDI recurrence for up to 12 months.

496. Secondary Prophylaxis for Clostridium difficile Infection: A Physician Practice Assessment

BackgroundRecurrent Clostridium difficile infection (CDI) is associated with significant morbidity, mortality and healthcare related costs. Up to 30% of CDI cases recur, resulting in 83,000 cases of recurrent CDI per year. Although agents for primary and secondary prophylaxis for CDI including the use of probiotics, antibiotics, fecal microbiota transplantations, and newer therapies such as bezlotoxumab have been reported, there is no consensus guidelines regarding their use. The purpose of this study was to assess physician practices regarding secondary prophylaxis for CDI.MethodsThis cross-sectional study using Qualtrics electronic survey (24 questions) assessed physician practice preferences. The survey was distributed through institutional emails and through the Infectious Disease Society of America “IDea Exchange” forum. Responses were collected and analyzed using descriptive statistics.ResultsA total of 246 surveys were completed. Physicians were surveyed from greater than 100 locations (see Figure 1). Most (229, 93%) of the physicians practiced in an inpatient setting. Respondent specialties were primarily infectious diseases (138, 56%) followed by internal medicine (72, 29%). Most physicians (173, 71%) use secondary prophylaxis for CDI prevention (see Figure 2). Vancomycin (121, 70%) and probiotics (114, 66%) were most commonly used for CDI secondary prophylaxis, (see Figure 3). Of 164 physicians who used secondary prophylaxis half of them (89, 54.2%), used prophylaxis only for patients with a history of recurrent CDI receiving antibiotics and about a third, (49, 29.9%) utilized it for patients with a history of CDI who were receiving antibiotics. ID physicians were more likely to prescribe secondary prophylaxis as compared with non-ID physicians (85% of 127 respondents vs. 75% of 85 respondents, P = 0.052). The use of secondary prophylaxis was similar among private practice and academic physicians (84% of 39 vs. 80% of 157 respondents, P = 0.591).ConclusionThe majority of the physicians who responded to this survey use secondary prophylaxis to prevent recurrent CDI, hence future CDI guidelines need to address the role of secondary prophylaxis in clinical practice. Disclosures All authors: No reported disclosures.

490. Comparison of Clostridium difficile Infection Outcomes by Diagnostic Testing Method

BackgroundUS laboratories are increasingly using nucleic acid amplification tests (NAAT) to diagnose Clostridium difficile infection (CDI) due to their increased sensitivity over toxin enzyme immunoassays (EIA), but NAATs may be more likely than toxin EIAs to detect colonization rather than true disease. Limited data indicate patients positive by toxin EIA (toxin+) have worse outcomes than those positive by NAAT (NAAT+) only, suggesting toxin EIA detects true infection more often than NAAT. We used multisite CDI surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program to compare clinical course and outcomes between toxin+ and NAAT+ only patients.MethodsA case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases detected during 2014–2015 by a testing algorithm using toxin EIA and NAAT were classified as toxin+ or NAAT+ only. Medical charts were reviewed. Death data were obtained from state death registries. Multivariable logistic regression models were used to compare CDI recurrence and 90-day mortality between the two groups, adjusting for age, sex, race, Charlson comorbidity index, and receipt of oral vancomycin. For the outcome of recurrence, we also adjusted for history of CDI in the prior 6 months.ResultsOf 4,878 cases, 2160 (44%) were toxin+ and 2,718 (56%) were NAAT+ only. Toxin+ cases were more likely than NAAT+ only cases to be ≥65 years old (48% vs. 38%; P < 0.0001), have white blood cells ≥15,000/µL (483/1,539 [31%] vs. 423/1,978 [21%]; P < 0.0001), and have received oral vancomycin ≤3 days of diagnosis (32% vs. 29%; P = 0.03). Comparing toxin+ to NAAT+ only cases, 21% vs. 11% had a recurrence (P < 0.0001), of which 71% vs. 33% had a toxin+ recurrence (P < 0.0001), and 10% vs. 9% died ≤90 days of diagnosis (P = 0.12). In multivariable analysis, a toxin+ result was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61–2.22) but not with 90-day mortality (aOR: 0.99; 95% CI: 0.81–1.22).ConclusionToxin+ CDI is more severe by some markers and more likely to recur as toxin+. However, there was no difference in adjusted mortality, which may reflect an effect on mortality in NAAT+ only cases from mild CDI, receipt of unnecessary CDI treatment, or other factors.Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Clostridium difficile in ulcerative colitis; a retrospective study

Aim : To study epidemiology and risk factors of Clostridium difficile infection (CDI) and its association with colectomy rates in patients with ulcerative colitis (UC). Materials and methods : We retrospectively analyzed medical files of 1179 patients with inflammatory bowel disease who had been treated from January 1 to December 31, 2017, in the Loginov Moscow Clinical Scientific Center (Moscow, Russia). UC was diagnosed according to the International Classification of Diseases, v. 10 (ICD10: K51). Final analysis included data from 400 UC patients. Depending on the presence of preliminary CDI diagnosis, the patients were divided into two groups: 79 (19.75%) patients with UC had at least one confirmed CDI episode, whereas 321 (80.25%) patients had no history of CDI. Results : CDI prevalence in UC patients was 19.75%, and 88.6% of the infectious episodes were community-acquired, whereas only 5.1% occurred in the inpatients. Mean (± SD) age at CDI occurrence in patients with inflammatory bowel disease was 37.8 ± 12.9 years. Only 13.4% of the patients with UC and associated CDI had the history of antibiotic therapy, and 40.5% had been previously treated with steroids. Prolonged immunosuppressive therapy in UC patients was associated with CDI: 41.8% of those with CDI had been treated with azathioprine/6-mercaptopurin for a long time, while among those without CDI this treatment had been administered only to 14.6% (p < 0.001). CDI prevalence in the UC patients who had been treated with mesenchymal stromal bone marrow cells was significantly lower than in those who had been treated with genetically engineered biological agents, both with and without immunosuppressants (p < 0.05). Surgery (colectomy) was necessary in 3 out of 4 patients with extremely severe UC associated with CDI, and in 2 out of 18 patients with extremely severe UC exacerbation without CDI. Conclusion : Young UC patients are more susceptible to CDI and often do not have any conventional CDI risk factors. In UC patients, other risk factors than in the general population, may have a significant impact on the CDI occurrence. UC patients with CDI more often have a history of salicylate failure, they more frequently require biological treatments, have lower mean albumin levels and higher activity of the inflammation. Extremely severe UC episode associated with CDI significantly increases the risk of colectomy.

Cost-Effectiveness Analysis of Bezlotoxumab Added to Standard of Care Versus Standard of Care Alone for the Prevention of Recurrent Clostridium difficile Infection in High-Risk Patients in Spain.

IntroductionClostridium difficile infection (CDI) is the major cause of infectious nosocomial diarrhoea and is associated with considerable morbidity, mortality and economic impact. Bezlotoxumab administered in combination with standard of care (SoC) antibiotic therapy prevents recurrent CDI. This study assessed the cost-effectiveness of bezlotoxumab added to SoC, compared to SoC alone, to prevent the recurrence of CDI in high-risk patients from the Spanish National Health System perspective.MethodsA Markov model was used to simulate the natural history of CDI over a lifetime horizon in five populations of patients at high risk of CDI recurrence according to MODIFY trials: (1) ≥ 65 years old; (2) severe CDI; (3) immunocompromised; (4) ≥ 1 CDI episode in the previous 6 months; and (5) ≥ 65 years old and with ≥ 1 CDI episode in the previous 6 months. The incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.ResultsIn all patient populations (from 1 to 5), bezlotoxumab added to SoC reduced CDI recurrence compared to SoC alone by 26.4, 19.5, 21.2, 26.6 and 39.7%, respectively. The resulting ICERs for the respective subgroups were €12,724, €17,495, €9545, €7386, and €4378. The model parameters with highest impact on the ICER were recurrence rate (first), mortality, and utility values. The probability that bezlotoxumab was cost-effective at a willingness-to-pay threshold of €21,000/QALY was 85.5%, 54.1%, 86.0%, 94.5%, 99.6%, respectively.ConclusionThe results suggest that bezlotoxumab added to SoC compared to SoC alone is a cost-effective treatment to prevent the recurrence of CDI in high-risk patients. The influence of changes in model parameters on DSA results was higher in patients ≥ 65 years old, with severe CDI and immunocompromised. Additionally, PSA estimated that the probability of cost-effectiveness exceeded 85% in most subgroups.FundingMerck Sharp & Dohme Corp.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0813-y) contains supplementary material, which is available to authorized users.

Insight into Fecal Microbiota Transplant in an Immunocompromised Patient

Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality. Fecal microbiota transplant (FMT) is effective for treatment of recurrent CDI, but has not been well studied in immunocompromised (IC) patients. New data shows that FMT may be safe in this population, but has not gained widespread acceptance. This is the case of a 67-year old male with recurrent CDI and immunocompromised state due to myelodysplastic syndrome transformed to acute myeloid leukemia, who was treated with FMT. This case contributes to the growing body of evidence on the outcomes of FMT on CDI in IC patients. The patient is a 67-year old male with past medical history significant for clostridium difficile colitis who was diagnosed with myelodysplastic syndrome with progression to acute myeloid leukemia. He developed diarrhea with ten loose, bloody bowel movements a day. Vitals on admission were unremarkable. On exam, he displayed left lower quadrant tenderness. Labs displayed WBC 1.43, hemoglobin 8.1, and platelets 126. He was treated initially with vancomycin, with the addition of metronidazole after minimal improvement. Stool studies were negative for infectious cause. Flexible sigmoidoscopy revealed the presence of pseudomembranes. Figures 1 and 2 show the heaped, necrotic epithelium characteristic of pseudomembranes in CDI. Due to the refractory CDI, the patient underwent FMT with improvement in his bowel movement frequency to three loose bowel movements a day. Conditioning therapy in preparation for stem cell transplant was initiated, but the patient suffered cardiorespiratory distress and died. FMT is an established treatment for recurrent CDI. One population in which FMT has not been well studied is in IC patients due to the high theoretical risk of complications. Recent studies have shown that FMT in IC patients results in resolution or decrease in diarrhea frequency with few adverse effects. Our patient met inclusion criteria for many of these studies with his history of immunosuppression and refractory CDI. After FMT, the patient's diarrhea frequency decreased from ten loose bowel movements to three a day. The patient was able to undergo conditioning therapy in preparation for stem cell transplant. Although our patient succumbed to cardiorespiratory distress, this case provides valuable insight into a patient population that is not normally treated with FMT and furthers the discussion on FMT in IC patients.1464_A Figure 1. Heaped, necrotic epithelium characteristic of pseudomembranes in clostridium difficile infection1464_B Figure 2. Magnification of Image 1

PIN35 - COST-EFFECTIVENESS OF BEZLOTOXUMAB FOR THE PREVENTION OF RECURRENCE OF CLOSTRIDIUM DIFFICILE INFECTION IN PORTUGAL

Clostridium difficile infection (CDI) is the most common known cause of nosocomial diarrhea associated with antibiotic use and 20 to 30% of the patients have recurrences. Its incidence has been increasing over the last few decades with a considerable morbidity and mortality as well as healthcare resource use from CDI patients. This study assesses the cost-effectiveness of bezlotoxumab, a new antitoxin agent + standard of care (SoC) compared with SoC alone in patients who are at risk for CDI recurrence. A state-transition Markov model was developed to simulate the natural history of CDI, over a lifetime horizon from the societal perspective. Patient characteristics and recurrence rates were taken from pooled data of the two Phase 3 clinical trials. The analysis was conducted in the entire clinical trial population representing the patients at risk of CDI recurrence. Costs and outcomes were estimated from Portuguese sources, and discounted annually at 5%, as recommended by national guidelines. Model outputs included discounted and undiscounted life years, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios (ICERs). In the base case analysis, the model predicted that treating patients with bezlotoxumab in addition to SoC, when compared to SoC alone, reduced CDI total recurrences by 38.0% with increments of 0.1301 discounted life years gained and 0.0839 discounted QALYs gained per patient. The incremental discounted costs were 2,296.00 €. Incremental discounted cost-effectiveness ratios were estimated at 17.643,77 € per life year gained and 27.373,07 € per QALY gained. Key influential parameters include CDI-specific mortality, cost of recurrences, quality of life multipliers and underlying recurrence rate. The analysis suggests that bezlotoxumab in combination with SoC is a cost-effective treatment in the Portuguese setting, reducing the disease and economic burden associated with CDI, through the prevention of recurrence of CDI in patients at risk for recurrence.