- Email: [email protected]
Do Statins Decrease the Severity of Clostridium Difficile Infection: A Retrospective Cohort Study in a Tertiary Medical Center?
using run charts and analyzed using a median line. Odds Ratios were calculated using logistic regression analysis. Results: During the intervention, compliance rates climbed to ~50 % at the intervention hospital, and in all 1114 patients were treated with Sacchaflor. CDAD prevalence went from a median of 3.6 % among patients treated with antibiotics in the baseline period to 1.3 % in the intervention period. Furthermore, usage of Sacchaflor was associated with a reduced risk of CDAD at the intervention hospital: OR=0.19 (95 % CI 0.07-0.39). At two control hospitals, the median prevalence did not change throughout the baseline and intervention period combined and at one control hospital the median prevalence declined from 3.5 % to 2.3 %, possibly reflecting simultaneous antibiotic stewardship programs in the Capital Region of Denmark. Patients in the evaluated departments were comparable with median ages varying from 72 to 77 years, and mean length of hospital stay varying from 6.9 to 11.9 days. A single serious adverse event occurred in the form of a case of Saccharomyces fungaemia. Conclusions: The results from this interventional nonrandomized study indicated that S. boulardii is effective in preventing CDAD in an unselected cohort of mainly elderly patients from departments of internal medicine, and also found that adverse events occur only rarely.
DETECTING OUTCOMES FROM CLOSTRIDIUM DIFFICILE SCREENING ON ADMISSION IN PATIENTS ADMITTED TO A BONE MARROW TRANSPLANT UNIT Janice Cho, Priya Sampathkumar, Maria T. Seville, Purna Kashyap Background: Clostridium difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. CDI rates in patients undergoing stem cell transplants can be up to 9-fold higher than other hospitalized patients. In the absence of screening on admission, it remains unclear if hospital-associated CDI is a result of previous colonization or newly acquired C. difficile. The overall aim of this study was to determine 1) nosocomial acquisition of C. difficile and 2) if early isolation of patients who screen positive for C. difficile on admission decreases hospital-associated CDI. Methods: Starting in 2010, patients admitted to the bone marrow transplant (BMT) unit at Mayo Clinic in Arizona (MCA) were screened for C. difficile colonization on a stool sample using a polymerase chain reaction (PCR) test; those who tested positive were placed in contact precautions (CP). Patients admitted from December 2012 to October 2013 were identified through retrospective review. C. difficile test results, hospital course and outcomes were recorded. Patients who developed diarrhea during their hospital stay were treated as CDI if they had screened positive on admission; those who had screened negative were re-tested. Results: There were 385 admissions to the BMT unit from December 2012 to October 2013; 57 (15%) patients screened positive for C. difficile at admission and were placed on CP. There were 184 episodes of diarrhea during the hospital stay. 32 diarrhea episodes were in patients known to be colonized with C. difficile. 12 patients who were negative on admission tested positive for C. difficile after development of diarrhea. Thus the nosocomial acquisition rate was 3.6% (12/328) among patients who screened negative and accounts for 27.3% (12/44) patients treated as hospital-onset CDI. The overall hospitalonset CDI rate of 11.4% (44/385) and newly acquired CDI rate of 3.6% (12/328) were both much lower as compared to the usual reported rate of ~20%. 52% of the 44 patients with CDI were treated with oral metronidazole. All patients had improvement in diarrhea with 66% (29/44) having complete resolution. There was no significant difference in recent antibiotic exposure (<4 weeks), or response to treatment among those who screened positive or negative for C. difficile on admission. Conclusion: Screening for C. difficile on admission allows for estimation of hospital acquisition of CDI. The majority of hospital onset CDI can be attributed to C. difficile colonization at admission. Institution of early isolation following screening appears to reduce nosocomial transmission of C. difficile in the BMT unit. Knowledge of C.difficile colonization at admission may be useful in guiding decisions about antimicrobial therapy and isolation. Table 1. Patient Characteristics
Sa1780 SPECIFIC HOSPITAL ROOMS ARE ASSOCIATED WITH INCREASED RISK FOR CLOSTRIDIUM DIFFICILE INFECTION Daniel E. Freedberg, Hojjat Salmasian, Timothy C. Wang, Julian A. Abrams Introduction: Clostridium difficile spores can be cultured from surfaces throughout the hospital environment and risk for C. difficile infection (CDI) in hospitalized patients depends in part on the local environmental spore burden. We conducted a retrospective study to determine whether we could identify specific hospital rooms associated with increased risk for CDI. Methods: Adult patients hospitalized from 2010 to 2015 were eligible for this study. Patients were excluded if they developed CDI within 48 hours of admission or had <48 hours of follow-up time. Patients who were hospitalized in rooms with fewer than 50 admissions during the study period were also excluded. The primary outcome was the roomspecific rate of CDI, with CDI defined as a newly positive stool PCR for the C. difficile toxin B gene followed by treatment for CDI. Analyses were stratified according to room type as standard (two or more patients) or intensive care unit (ICU, all single-occupancy). To determine whether some rooms had more CDI than expected, room-specific CDI rates were modeled against a normal Gaussian distribution and the data was inspected for significant outliers. The room-specific rates of CDI were compared between outlier rooms and other rooms, and the data was interrogated for spatiotemporal clustering of CDI cases in outlier rooms. Results: The study included 23 separate wards (260 rooms) and 9 distinct ICUs (124 rooms). The incidence rate of CDI was 365/64,805 (0.6%) and 280/11,285 (2.5%) in standard and ICU rooms respectively. There were 5 standard rooms and 3 ICU rooms with greater than expected rates of CDI (Figure). Of these outliers, each standard room had 4 or more cases of CDI and each ICU rooms had 6 or more cases of CDI. For the outlier standard rooms, the room-specific CDI rates were all >3.3 standard deviations (SD) above the mean rate for standard rooms (a 4.8-fold difference). For the outlier ICU rooms, the room-specific CDI rates were all >2.7 SD above the mean rate or ICU rooms (a 3.4-fold difference). Spatiotemporal analysis of the outlier rooms showed that the 3 outlier ICU rooms were in a single ICU and were immediately adjacent to each other. Conclusions: Specific hospital rooms in close spatial proximity were associated with increased risk for CDI. These rooms may serve as a reservoir for C. difficile spores and are a potential target for interventions seeking to decrease rates of healthcare-associated CDI.
Table 2. Prior CDI in patients admitted to BMT (Total N=385)
Sa1781 DO STATINS DECREASE THE SEVERITY OF CLOSTRIDIUM DIFFICILE INFECTION: A RETROSPECTIVE COHORT STUDY IN A TERTIARY MEDICAL CENTER? Sanna Fatima, Basma AbdulHadi, Ramzi Mulki, Supakanya Wongrakpanich, Philip Katz Background: Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea. It is a devastating disease with increasing incidence, mortality and cost over the past few decades. The growing search for risk factors for CDI has shown that statins play a protective role in preventing CDI. This is attributed to their pleiotropic and anti-inflammatory effect on tissues. Prior studies have shown that statins decrease the incidence, recurrence and mortality of CDI; however very limited data exists with regards to effect of statins on the severity of CDI. Aim: The intent of this study is to evaluate if statin use has a protective effect on the severity of CDI. Methods: We conducted a retrospective cohort study of patients admitted to our medical center between January 2013 - June 2015 diagnosed with CDI. Patients were divided into two groups based on the severity of their illness; mildmoderate and severe-complicated, according to the 2013 ACG criteria of CDI severity (1). Patients with HIV, history of transplant, end stage renal disease, end stage liver disease, and incomplete records were excluded. The relationship between statin use and the severity of CDI was analyzed using a Chi-square test. Results: Of the 196 cases, the majority of CDI occurred in males (n=84) and African Americans (n=120) with an average age of 64.52 years (±16.43). About 56.1% (n=110) of the cohort had severe CDI. We compared the severity of disease between 65 (33.7%) statin users and 130 (66.3%) non-users. We found that statin use had no significant impact on the severity of CDI (Figure 1). We further
Sa1779 USE OF PROPHYLACTIC SACCHAROMYCES BOULARDI I TO PREVENT CLOSTRIDIUM DIFFICILE INFECTION: A PROSPECTIVE INTERVENTION STUDY Jeppe W. Carstensen, Mahtab Chehri, Kristian Schønning, Steen C. Rasmussen, Jacob Anhøj, Christian Andersen, Andreas M. Petersen Background: Clostridium difficile-associated diarrhea (CDAD) is a common complication to antibiotic use in hospitals. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDAD in unselected hospitalized patients treated with antibiotics. Methods: We conducted a prospective open controlled intervention study, starting October 2014, aiming to prescribe Sacchaflor (S. boularidii 5x109 + 200 mg Mannan Oligo Saccharides) twice daily to patients treated with antibiotics in three internal medicine departments. In the period November 2014 to October 2015, all occurrences of CDAD in patients receiving antibiotics were reported and compared to a baseline period defined as two years prior, as well as internal medicine departments in three other acute emergency hospitals in the Capital Region of Denmark. Results were plotted
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compared intensity of statin dose (low, moderate, severe) with the severity of CDI and found no statistically significant correlation (p-value=0.637). Discussion: Our study did not show any significant association between statin use and the severity of CDI consistent with prior observation (2). Larger prospective studies need to be done to elucidate this relationship because if a protective relationship does exist, prescribing a relatively safe and inexpensive statin could prevent morbidity associated with CDI. References: 1. Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108: 478-498. 2. Atamna A, Yahav D, Eliakim-Raz N et al. The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients. Eur J Clin Microbiol Infect Dis. 2016 May;35(5):779-84
analyzed using fixed effect model. Publication bias was assessed using Egger's test and adjusted using trim and fill test. Quality assessment of studies was done using NIH Quality assessment tool for before-after studies. RESULTS: A total of 4 studies (two prospective and two retrospective) with total 239 patients were included in the analysis. One study was of good quality while the remaining three were of fair quality as per NIH scale. WPR for clinical resolution after the single treatment was 79% (72%, 84%), with low heterogeneity (I2=10%). Egger's test failed to detect any publication bias (P =0.44). WPR for clinical resolution after a second treatment was 91% (86%, 94%), with no heterogeneity (I2=0%). Publication bias was detected by Egger's test (P=0.02), and adjusted effect size was 90% (87%, 93%). WPR for relapse was 10% (7%, 15%), with no heterogeneity and no publication bias (P=0.38). During a follow up ranging from 3-6 months, mild diarrhea (not CDI and not requiring hospitalization) was the most common adverse event (46%), which was followed by transient abdominal pain, bloating and nausea (39%) and fatigue in 22%. Only 4 patients developed fever of which one patient required hospitalization. CONCLUSIONS: Orally administered, capsulized, frozen FMT provides a promising, effective, safe and convenient option for treatment of recurrent CDI.
Figure 1: Association of statin use with the severity of CDI
Sa1782 OUTCOMES AND MANAGEMENT OF PATIENTS WITH FAILED FECAL MICROBIOTA TRANSPLANTATION FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION Raseen Tariq, Darrell S. Pardi, Renee M. Weatherly, Patricia P. Kammer, Sahil Khanna Background: Fecal Microbiota Transplantation (FMT) has emerged as a safe and effective treatment for recurrent Clostridium difficile infection (CDI) with success rates >85%. However, data on management and clinical outcomes of patients who have recurrent CDI after FMT are limited. In this study, we report our experience with management and outcomes of patients with failed FMT. Methods: All patients who underwent FMT for recurrent CDI from August 2012 to September 2016 were included. Donor and recipient screening was performed using a standard protocol and recurrent CDI treatment was stopped 24 hours before FMT. Patients who received FMT were prospectively contacted; a standardized questionnaire was used to evaluate their symptom resolution and patients were instructed to call with recurrent diarrhea. FMT failure was defined as recurrent diarrhea with a positive C. difficile stool test. Clinical data including demographics, comorbid conditions, donor information, FMT route, post-FMT systemic antibiotic exposure and post-FMT CDI management were collected and analyzed. Results: After a median follow-up of 79.4 weeks (range 4-209 weeks), of the 445 recurrent CDI patients who underwent FMT, 55 (12.3%; median age 56 years [range 20-90]; 52.6% female) had subsequent recurrent CDI. Among these 55 patients, 18 (32.7%) were immunocompromised, 17 (30.9%) had underlying Inflammatory Bowel Disease (IBD), 6 (10.9%) had Irritable Bowel Syndrome, 21 (36.8%) were on proton pump inhibitors before FMT, 23 (40.3%) had history of CDI related hospitalization before FMT, and 4 were hospitalized with severe or severe-complicated CDI at the time of FMT. Standard unrelated donors were used in 54 (98.1%) patients and colonoscopy was the most common instillation route (96.3%). Among FMT failures, post-FMT 16 patients (29.9%) had recurrence of symptoms within 3 months. The median time to recurrent CDI after FMT was 164 days (23.5 weeks) (range 1.1-152.1 weeks). Concomitant antibiotics were used after FMT in 29 patients (52.7%). Of the patients who failed FMT, 32.7% were immunocompromised and 30.9% had underlying IBD. Of the patients who failed FMT, 26 (47.2%) were managed with a 2nd FMT, 28 (50.9%) with antibiotics and 1 (1.8%) was managed surgically. Among the patients managed with antibiotics, 1 (3.5%) was treated with metronidazole, 1 (3.5%) with both vancomycin and metronidazole, 17 (60.7%) with vancomycin and 9 (32.1%) with fidaxomicin. Two patients had recurrent CDI after 2nd FMT (7.7%), 1 who was managed successfully with fidaxomicin and 1 who was treated successfully with a 3rd FMT. Conclusions: CDI recurred in 12.3% patients after FMT. The most common reasons include repeat antibiotic exposure, immunosuppression and underlying IBD. Patients with FMT failure can usually be managed with repeat antibiotics or repeat FMT.
Fig. 1: Forest plots for clinical success after single treatment and second treatment.
Fig. 3: Forest plot to evaluate relapse rate after one successful treatment
Sa1784 ADVERSE EFFECTS OF LIQUID VS. ENCAPSULATED LYOPHILIZED FULLSPECTRUM MICROBIOTA FOR THE TREATMENT OF CLOSTRIDIUM DIFFICILE INFECTION Scott W. Mitchell, Prathibha DeZoysa, Sharyn Leis, Avindra F. Jayewardene, Priya Maistry, Safaa Gadalla, Thomas J. Borody Introduction The use of Fecal Microbiota Transplantation (FMT) is an established treatment of Clostridium difficile infection (CDI) and is being trialled for a range of gastrointestinal (GI) and non-GI related conditions. FMT is believed to eradicate some GI infections and promote microbial restitution by correcting the gut microbiome dysbiosis, such as that caused by CDI. Adverse events (AEs) may occur with the use of liquid and frozen FMT1. However, AE's during CDI treatment with encapsulated lyophilized (freeze-dried) full-spectrum microbiota (L-FSM) have not been compared with AE's using liquid FMT despite their efficacy in treating CDI2. Aim To compare the AEs of liquid FMT vs. encapsulated L-FSM used in the treatment of patients with CDI. Methods A retrospective analysis of AE's was conducted in a cohort of patients treated with liquid FMT and compared with an age (±4 years) and sex-matched cohort treated with encapsulated L-FSM for initial and recurrent CDI. Liquid FMT was administered over 2 days via transcolonoscopic infusion followed by a rectal enema (n=10) while the encapsulated L-FSM was administered as 6-8 capsules over 1-3 days (n = 10). For a month following the conclusion of the respective therapies AEs were collected using a standardised questionnaire. Results Treatment with liquid FMT resulted in more AEs overall (n=14) compared with L-FSM treatment (n=10), although this difference was not statistically significant (p=0.414). The most common AE in the liquid FMT cohort was abdominal cramps and/or pain (n=3) compared to that of encapsulated LFSM (n=4). However, occurrences of blood and/or mucus in stool was higher in liquid FMT (n=3) than in the encapsulated L-FSM cohort (n=2). Further, leakage was prevalent in 2 patients in liquid FMT compared to none in the encapsulated L-FSM cohort. None of the patients in either cohort experienced vomiting. It is possible for the AEs experienced to be part of the CDI symptom complex. Conclusions 1. Patients using encapsulated L-FSM experienced numerically fewer AEs overall when compared to the liquid FMT cohort. 2. Many future FMTs will utilize an encapsulated product and so fewer AEs are expected. 3. Comparison of larger cohorts especially using repeated FMT's may show significantly fewer AEs in the lyophilised cohort, and this may demonstrate why AEs occur and how to treat and prevent AEs. References 1Wang, S., Mengque, X., & Wang, W., et al. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016; 11(8): e0161174.
Sa1783 EFFICACY AND SAFETY OF ORAL, CAPSULIZED, FROZEN FECAL MICROBIOTA TRANSPLANTATION FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION. A SYSTEMATIC REVIEW AND META-ANALYSIS Tariq A. Hammad, Muhammad Ali Khan, Khaled Srour, Thaer Abdelfattah, Yaseen Alastal, Wade M. Lee, Thomas Sodeman, Ali Nawras BACKGOUND: Clostridium difficile infection (CDI) has significant clinical and economic burdens. Management of recurrent CDI is a challenging field. Fecal microbiota transplantation (FMT) for recurrent CDI has been consistently showing promising results. FMT has been mainly administered though colonoscopy or nasogastric/duodenal instillation routes. More recently, orally administered, capsulized, frozen FMT has been used. OBJECTIVES: We conducted this systematic review and meta-analysis to assess the efficacy (Clinical resolution without relapse) and safety (FMT related adverse events) of orally administered, capsulized, frozen FMT in recurrent CDI. METHODS: PubMed/MEDLINE, Embase, Web of Science Core Collection, and Cochrane Register of Controlled Trials from inception to Nov 30, 2016 were systematically searched for studies (with ≥10patients) on orally administered, capsulized, frozen FMT in recurrent CDI with clear outcomes. We estimated weighted pooled rates (WPR) [with 95% confidence interval (CI)] of clinical resolution after single treatment without recurrence of the infection in 8 weeks and clinical success after a second treatment. WPR was also calculated for relapse after successful treatment (within 8 weeks). These were
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DETECTING OUTCOMES FROM CLOSTRIDIUM DIFFICILE SCREENING ON ADMISSION IN PATIENTS ADMITTED TO A BONE MARROW TRANSPLANT UNIT Janice Cho, Priya Sampathkumar, Maria T. Seville, Purna Kashyap Background: Clostridium difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. CDI rates in patients undergoing stem cell transplants can be up to 9-fold higher than other hospitalized patients. In the absence of screening on admission, it remains unclear if hospital-associated CDI is a result of previous colonization or newly acquired C. difficile. The overall aim of this study was to determine 1) nosocomial acquisition of C. difficile and 2) if early isolation of patients who screen positive for C. difficile on admission decreases hospital-associated CDI. Methods: Starting in 2010, patients admitted to the bone marrow transplant (BMT) unit at Mayo Clinic in Arizona (MCA) were screened for C. difficile colonization on a stool sample using a polymerase chain reaction (PCR) test; those who tested positive were placed in contact precautions (CP). Patients admitted from December 2012 to October 2013 were identified through retrospective review. C. difficile test results, hospital course and outcomes were recorded. Patients who developed diarrhea during their hospital stay were treated as CDI if they had screened positive on admission; those who had screened negative were re-tested. Results: There were 385 admissions to the BMT unit from December 2012 to October 2013; 57 (15%) patients screened positive for C. difficile at admission and were placed on CP. There were 184 episodes of diarrhea during the hospital stay. 32 diarrhea episodes were in patients known to be colonized with C. difficile. 12 patients who were negative on admission tested positive for C. difficile after development of diarrhea. Thus the nosocomial acquisition rate was 3.6% (12/328) among patients who screened negative and accounts for 27.3% (12/44) patients treated as hospital-onset CDI. The overall hospitalonset CDI rate of 11.4% (44/385) and newly acquired CDI rate of 3.6% (12/328) were both much lower as compared to the usual reported rate of ~20%. 52% of the 44 patients with CDI were treated with oral metronidazole. All patients had improvement in diarrhea with 66% (29/44) having complete resolution. There was no significant difference in recent antibiotic exposure (<4 weeks), or response to treatment among those who screened positive or negative for C. difficile on admission. Conclusion: Screening for C. difficile on admission allows for estimation of hospital acquisition of CDI. The majority of hospital onset CDI can be attributed to C. difficile colonization at admission. Institution of early isolation following screening appears to reduce nosocomial transmission of C. difficile in the BMT unit. Knowledge of C.difficile colonization at admission may be useful in guiding decisions about antimicrobial therapy and isolation. Table 1. Patient Characteristics
Sa1780 SPECIFIC HOSPITAL ROOMS ARE ASSOCIATED WITH INCREASED RISK FOR CLOSTRIDIUM DIFFICILE INFECTION Daniel E. Freedberg, Hojjat Salmasian, Timothy C. Wang, Julian A. Abrams Introduction: Clostridium difficile spores can be cultured from surfaces throughout the hospital environment and risk for C. difficile infection (CDI) in hospitalized patients depends in part on the local environmental spore burden. We conducted a retrospective study to determine whether we could identify specific hospital rooms associated with increased risk for CDI. Methods: Adult patients hospitalized from 2010 to 2015 were eligible for this study. Patients were excluded if they developed CDI within 48 hours of admission or had <48 hours of follow-up time. Patients who were hospitalized in rooms with fewer than 50 admissions during the study period were also excluded. The primary outcome was the roomspecific rate of CDI, with CDI defined as a newly positive stool PCR for the C. difficile toxin B gene followed by treatment for CDI. Analyses were stratified according to room type as standard (two or more patients) or intensive care unit (ICU, all single-occupancy). To determine whether some rooms had more CDI than expected, room-specific CDI rates were modeled against a normal Gaussian distribution and the data was inspected for significant outliers. The room-specific rates of CDI were compared between outlier rooms and other rooms, and the data was interrogated for spatiotemporal clustering of CDI cases in outlier rooms. Results: The study included 23 separate wards (260 rooms) and 9 distinct ICUs (124 rooms). The incidence rate of CDI was 365/64,805 (0.6%) and 280/11,285 (2.5%) in standard and ICU rooms respectively. There were 5 standard rooms and 3 ICU rooms with greater than expected rates of CDI (Figure). Of these outliers, each standard room had 4 or more cases of CDI and each ICU rooms had 6 or more cases of CDI. For the outlier standard rooms, the room-specific CDI rates were all >3.3 standard deviations (SD) above the mean rate for standard rooms (a 4.8-fold difference). For the outlier ICU rooms, the room-specific CDI rates were all >2.7 SD above the mean rate or ICU rooms (a 3.4-fold difference). Spatiotemporal analysis of the outlier rooms showed that the 3 outlier ICU rooms were in a single ICU and were immediately adjacent to each other. Conclusions: Specific hospital rooms in close spatial proximity were associated with increased risk for CDI. These rooms may serve as a reservoir for C. difficile spores and are a potential target for interventions seeking to decrease rates of healthcare-associated CDI.
Table 2. Prior CDI in patients admitted to BMT (Total N=385)
Sa1781 DO STATINS DECREASE THE SEVERITY OF CLOSTRIDIUM DIFFICILE INFECTION: A RETROSPECTIVE COHORT STUDY IN A TERTIARY MEDICAL CENTER? Sanna Fatima, Basma AbdulHadi, Ramzi Mulki, Supakanya Wongrakpanich, Philip Katz Background: Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea. It is a devastating disease with increasing incidence, mortality and cost over the past few decades. The growing search for risk factors for CDI has shown that statins play a protective role in preventing CDI. This is attributed to their pleiotropic and anti-inflammatory effect on tissues. Prior studies have shown that statins decrease the incidence, recurrence and mortality of CDI; however very limited data exists with regards to effect of statins on the severity of CDI. Aim: The intent of this study is to evaluate if statin use has a protective effect on the severity of CDI. Methods: We conducted a retrospective cohort study of patients admitted to our medical center between January 2013 - June 2015 diagnosed with CDI. Patients were divided into two groups based on the severity of their illness; mildmoderate and severe-complicated, according to the 2013 ACG criteria of CDI severity (1). Patients with HIV, history of transplant, end stage renal disease, end stage liver disease, and incomplete records were excluded. The relationship between statin use and the severity of CDI was analyzed using a Chi-square test. Results: Of the 196 cases, the majority of CDI occurred in males (n=84) and African Americans (n=120) with an average age of 64.52 years (±16.43). About 56.1% (n=110) of the cohort had severe CDI. We compared the severity of disease between 65 (33.7%) statin users and 130 (66.3%) non-users. We found that statin use had no significant impact on the severity of CDI (Figure 1). We further
Sa1779 USE OF PROPHYLACTIC SACCHAROMYCES BOULARDI I TO PREVENT CLOSTRIDIUM DIFFICILE INFECTION: A PROSPECTIVE INTERVENTION STUDY Jeppe W. Carstensen, Mahtab Chehri, Kristian Schønning, Steen C. Rasmussen, Jacob Anhøj, Christian Andersen, Andreas M. Petersen Background: Clostridium difficile-associated diarrhea (CDAD) is a common complication to antibiotic use in hospitals. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDAD in unselected hospitalized patients treated with antibiotics. Methods: We conducted a prospective open controlled intervention study, starting October 2014, aiming to prescribe Sacchaflor (S. boularidii 5x109 + 200 mg Mannan Oligo Saccharides) twice daily to patients treated with antibiotics in three internal medicine departments. In the period November 2014 to October 2015, all occurrences of CDAD in patients receiving antibiotics were reported and compared to a baseline period defined as two years prior, as well as internal medicine departments in three other acute emergency hospitals in the Capital Region of Denmark. Results were plotted
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compared intensity of statin dose (low, moderate, severe) with the severity of CDI and found no statistically significant correlation (p-value=0.637). Discussion: Our study did not show any significant association between statin use and the severity of CDI consistent with prior observation (2). Larger prospective studies need to be done to elucidate this relationship because if a protective relationship does exist, prescribing a relatively safe and inexpensive statin could prevent morbidity associated with CDI. References: 1. Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108: 478-498. 2. Atamna A, Yahav D, Eliakim-Raz N et al. The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients. Eur J Clin Microbiol Infect Dis. 2016 May;35(5):779-84
analyzed using fixed effect model. Publication bias was assessed using Egger's test and adjusted using trim and fill test. Quality assessment of studies was done using NIH Quality assessment tool for before-after studies. RESULTS: A total of 4 studies (two prospective and two retrospective) with total 239 patients were included in the analysis. One study was of good quality while the remaining three were of fair quality as per NIH scale. WPR for clinical resolution after the single treatment was 79% (72%, 84%), with low heterogeneity (I2=10%). Egger's test failed to detect any publication bias (P =0.44). WPR for clinical resolution after a second treatment was 91% (86%, 94%), with no heterogeneity (I2=0%). Publication bias was detected by Egger's test (P=0.02), and adjusted effect size was 90% (87%, 93%). WPR for relapse was 10% (7%, 15%), with no heterogeneity and no publication bias (P=0.38). During a follow up ranging from 3-6 months, mild diarrhea (not CDI and not requiring hospitalization) was the most common adverse event (46%), which was followed by transient abdominal pain, bloating and nausea (39%) and fatigue in 22%. Only 4 patients developed fever of which one patient required hospitalization. CONCLUSIONS: Orally administered, capsulized, frozen FMT provides a promising, effective, safe and convenient option for treatment of recurrent CDI.
Figure 1: Association of statin use with the severity of CDI
Sa1782 OUTCOMES AND MANAGEMENT OF PATIENTS WITH FAILED FECAL MICROBIOTA TRANSPLANTATION FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION Raseen Tariq, Darrell S. Pardi, Renee M. Weatherly, Patricia P. Kammer, Sahil Khanna Background: Fecal Microbiota Transplantation (FMT) has emerged as a safe and effective treatment for recurrent Clostridium difficile infection (CDI) with success rates >85%. However, data on management and clinical outcomes of patients who have recurrent CDI after FMT are limited. In this study, we report our experience with management and outcomes of patients with failed FMT. Methods: All patients who underwent FMT for recurrent CDI from August 2012 to September 2016 were included. Donor and recipient screening was performed using a standard protocol and recurrent CDI treatment was stopped 24 hours before FMT. Patients who received FMT were prospectively contacted; a standardized questionnaire was used to evaluate their symptom resolution and patients were instructed to call with recurrent diarrhea. FMT failure was defined as recurrent diarrhea with a positive C. difficile stool test. Clinical data including demographics, comorbid conditions, donor information, FMT route, post-FMT systemic antibiotic exposure and post-FMT CDI management were collected and analyzed. Results: After a median follow-up of 79.4 weeks (range 4-209 weeks), of the 445 recurrent CDI patients who underwent FMT, 55 (12.3%; median age 56 years [range 20-90]; 52.6% female) had subsequent recurrent CDI. Among these 55 patients, 18 (32.7%) were immunocompromised, 17 (30.9%) had underlying Inflammatory Bowel Disease (IBD), 6 (10.9%) had Irritable Bowel Syndrome, 21 (36.8%) were on proton pump inhibitors before FMT, 23 (40.3%) had history of CDI related hospitalization before FMT, and 4 were hospitalized with severe or severe-complicated CDI at the time of FMT. Standard unrelated donors were used in 54 (98.1%) patients and colonoscopy was the most common instillation route (96.3%). Among FMT failures, post-FMT 16 patients (29.9%) had recurrence of symptoms within 3 months. The median time to recurrent CDI after FMT was 164 days (23.5 weeks) (range 1.1-152.1 weeks). Concomitant antibiotics were used after FMT in 29 patients (52.7%). Of the patients who failed FMT, 32.7% were immunocompromised and 30.9% had underlying IBD. Of the patients who failed FMT, 26 (47.2%) were managed with a 2nd FMT, 28 (50.9%) with antibiotics and 1 (1.8%) was managed surgically. Among the patients managed with antibiotics, 1 (3.5%) was treated with metronidazole, 1 (3.5%) with both vancomycin and metronidazole, 17 (60.7%) with vancomycin and 9 (32.1%) with fidaxomicin. Two patients had recurrent CDI after 2nd FMT (7.7%), 1 who was managed successfully with fidaxomicin and 1 who was treated successfully with a 3rd FMT. Conclusions: CDI recurred in 12.3% patients after FMT. The most common reasons include repeat antibiotic exposure, immunosuppression and underlying IBD. Patients with FMT failure can usually be managed with repeat antibiotics or repeat FMT.
Fig. 1: Forest plots for clinical success after single treatment and second treatment.
Fig. 3: Forest plot to evaluate relapse rate after one successful treatment
Sa1784 ADVERSE EFFECTS OF LIQUID VS. ENCAPSULATED LYOPHILIZED FULLSPECTRUM MICROBIOTA FOR THE TREATMENT OF CLOSTRIDIUM DIFFICILE INFECTION Scott W. Mitchell, Prathibha DeZoysa, Sharyn Leis, Avindra F. Jayewardene, Priya Maistry, Safaa Gadalla, Thomas J. Borody Introduction The use of Fecal Microbiota Transplantation (FMT) is an established treatment of Clostridium difficile infection (CDI) and is being trialled for a range of gastrointestinal (GI) and non-GI related conditions. FMT is believed to eradicate some GI infections and promote microbial restitution by correcting the gut microbiome dysbiosis, such as that caused by CDI. Adverse events (AEs) may occur with the use of liquid and frozen FMT1. However, AE's during CDI treatment with encapsulated lyophilized (freeze-dried) full-spectrum microbiota (L-FSM) have not been compared with AE's using liquid FMT despite their efficacy in treating CDI2. Aim To compare the AEs of liquid FMT vs. encapsulated L-FSM used in the treatment of patients with CDI. Methods A retrospective analysis of AE's was conducted in a cohort of patients treated with liquid FMT and compared with an age (±4 years) and sex-matched cohort treated with encapsulated L-FSM for initial and recurrent CDI. Liquid FMT was administered over 2 days via transcolonoscopic infusion followed by a rectal enema (n=10) while the encapsulated L-FSM was administered as 6-8 capsules over 1-3 days (n = 10). For a month following the conclusion of the respective therapies AEs were collected using a standardised questionnaire. Results Treatment with liquid FMT resulted in more AEs overall (n=14) compared with L-FSM treatment (n=10), although this difference was not statistically significant (p=0.414). The most common AE in the liquid FMT cohort was abdominal cramps and/or pain (n=3) compared to that of encapsulated LFSM (n=4). However, occurrences of blood and/or mucus in stool was higher in liquid FMT (n=3) than in the encapsulated L-FSM cohort (n=2). Further, leakage was prevalent in 2 patients in liquid FMT compared to none in the encapsulated L-FSM cohort. None of the patients in either cohort experienced vomiting. It is possible for the AEs experienced to be part of the CDI symptom complex. Conclusions 1. Patients using encapsulated L-FSM experienced numerically fewer AEs overall when compared to the liquid FMT cohort. 2. Many future FMTs will utilize an encapsulated product and so fewer AEs are expected. 3. Comparison of larger cohorts especially using repeated FMT's may show significantly fewer AEs in the lyophilised cohort, and this may demonstrate why AEs occur and how to treat and prevent AEs. References 1Wang, S., Mengque, X., & Wang, W., et al. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016; 11(8): e0161174.
Sa1783 EFFICACY AND SAFETY OF ORAL, CAPSULIZED, FROZEN FECAL MICROBIOTA TRANSPLANTATION FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION. A SYSTEMATIC REVIEW AND META-ANALYSIS Tariq A. Hammad, Muhammad Ali Khan, Khaled Srour, Thaer Abdelfattah, Yaseen Alastal, Wade M. Lee, Thomas Sodeman, Ali Nawras BACKGOUND: Clostridium difficile infection (CDI) has significant clinical and economic burdens. Management of recurrent CDI is a challenging field. Fecal microbiota transplantation (FMT) for recurrent CDI has been consistently showing promising results. FMT has been mainly administered though colonoscopy or nasogastric/duodenal instillation routes. More recently, orally administered, capsulized, frozen FMT has been used. OBJECTIVES: We conducted this systematic review and meta-analysis to assess the efficacy (Clinical resolution without relapse) and safety (FMT related adverse events) of orally administered, capsulized, frozen FMT in recurrent CDI. METHODS: PubMed/MEDLINE, Embase, Web of Science Core Collection, and Cochrane Register of Controlled Trials from inception to Nov 30, 2016 were systematically searched for studies (with ≥10patients) on orally administered, capsulized, frozen FMT in recurrent CDI with clear outcomes. We estimated weighted pooled rates (WPR) [with 95% confidence interval (CI)] of clinical resolution after single treatment without recurrence of the infection in 8 weeks and clinical success after a second treatment. WPR was also calculated for relapse after successful treatment (within 8 weeks). These were
AGA Abstracts
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