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Su1746 Predictors of Failure of Fecal Microbiota Transplantation (FMT) in the Management of Recurrent Clostridium difficile Infection
AGA Abstracts
There was no significant difference at the 95% level among the six cryoprotectant formulations trialled. Conclusion: The choice of cryoprotectant did not make a statistically significant difference to total cell viability in FMT product after lyophilization. However, it is not known whether the lack of a statistically significant difference will translate to equivalent FMT product efficacy in, for example, the treatment of C. difficile infection. In addition, it is possible that the lyophilization process, including the choice of cryoprotectant might affect viability of different groups of FMT bacteria differently, and this bears further study. References: 1. van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. The New England Journal of Medicine. 2013 Jan 31; 368(5): 407-415 Bacterial Indices Following Lyophilization
Figure 2: Two-way sensitivity analysis on probability of death from surgery and incrementally decreasing efficacy of the Fischer protocol. Abbreviations: FMT, fecal microbiota transplantation.
Su1746 Predictors of Failure of Fecal Microbiota Transplantation (FMT) in the Management of Recurrent Clostridium difficile Infection Joseph Dimitry, Ammar H. Keshteli, Dina Kao Background: Fecal microbiota transplantation (FMT) is a safe and effective alternative therapy for patients with recurrent C. diff infection (RCDI), with an overall success rate of 80-90% with one treatment. However, no clinical factors have been identified to predict those who may not respond to FMT. Aim: To identify predictive factors of treatment failure following a single or multiple FMT in RCDI. Methods: This retrospective study included 136 patients who received FMT for RCDI (defined as having at least 3 episodes of CDI) or severe/ complicated CDI, between Oct 2012 and Apr 2015 at the UAH hospital, with at least 3 months of follow-up. Success of FMT was defined as absence of CDI recurrence during the 3 month F/U. Failure was defined as recurrence of diarrhea associated with postive C diff toxin within 3 months of FMT. Those who failed 1 FMT were offered the 2nd FMT during F/U. Patient baseline characteristics, past medical history, medication use (including antibiotic use within 3 months following FMT), CDI classification, severity, and response to therapy, in addition to laboratory data were extracted from in-patient charts and outpatient electronic medical records. Results: Of the 136 patients, 106 (77.9%) were cured following one FMT. Of the 30 patients (22.1%) who failed the first FMT, 25 received a second FMT and 16 were cured. Univariate analysis was performed and the results shown in Table 1. It identified 7 factors to be associated with failure following 1 FMT. Multivariate analysis revealed that inpatient status at the time of FMT (OR 7.4; 95% CI 2.2-24.6, p=0.001), immunosuppresion (OR 4.5; 95% CI 1.3-16.2, p=0.020), and severe/complicated CDI (OR 5.2; 95% CI 1.221.6, p=0.025) were factors most independently associated with failure following 1 FMT. All 9 refractory CDI patients failed the 1st FMT. Antibiotic use within 3 months after FMT, chronic PPI use, duration or episodes of RCDI were not found to be predictors of FMT failure. Conclusion: Inpatient status at the time of FMT, immunosuppression, and severe/ complicated CDI are independent predictor of treatment failure following 1 FMT for CDI. Due to the fact that only a small number of patients failed at least 2 FMT, no predictive factors could be identified for those who failed despite multiple FMT. Interestingly, antibiotic use within 3 months post-FMT or chronic PPI use did not predict FMT failure. Further study with a larger sample size may identify predictors to identify those who may fail despite having at least 2 FMTs. Table 1
Su1745 The Cost-Effectiveness of Competing Strategies for Treating SevereComplicated Clostridium difficile Infection: Comparing Fecal Microbiota Transplantation With Standard Colectomy Liem B. Luong Nguyen, Majdi Osman, Austin L. Chiang, Carolyn Edelstein, Monika Fischer, Ashwin N. Ananthakrishnan, Jessica R. Allegretti, Mark Smith, Zain Kassam Background The clinical and economic burden of severe-complicated Clostridium difficile infection (CDI) is substantial. Colectomy, the current standard of care, carries significant mortality and cost. Recently, evidence suggests a sequential fecal microbiota transplantation (FMT) and antibiotic approach is a highly effective treatment for severe-complicated CDI. However, the cost-effectiveness has not been examined. Accordingly, we aim to compare the cost-effectiveness of FMT versus standard colectomy for treating severe-complicated CDI. Methods We developed a decision analysis model comparing 3 treatment strategies for severe-complicated CDI patients after failing standard intravenous metronidazole as well as oral and rectal vancomycin per guidelines: 1) Sequential FMT by flexible sigmoidoscopy with the need for repeat FMT, to a maximum of 3, and continued vancomycin guided by clinical response and pseudomembranes at endoscopic assessment as described in the literature (Fischer protocol), 2) Single FMT by flexible sigmoidoscopy and 3) Total colectomy and ileostomy. Given the dearth of efficacy data on sequential FMT in severe-complicated CDI, we conducted sensitivity analysis on clinical cure rates of FMT, reducing the expected efficacy by half at each stage of the Fischer protocol. Willingness-to-pay threshold was set at $50,000 per quality-adjusted life-year. All costs were adjusted to 2015 US and analysis was conducted from a societal perspective capturing direct costs at the time of discharge. Results In our model the sequential FMT approach was the most cost-effective strategy to treat severe-complicated CDI compared to a single FMT or standard colectomy (Figure 1). The total cost of the colectomy strategy was 67,422 USD which was significantly higher then the total cost of either FMT strategy (Fischer protocol: 26,700 USD, single FMT: 25,350 USD), each strategy driven by the cost of hospitalization. However, the Fischer protocol was 68% more effective than a single FMT and 56% more effective than colectomy. Colectomy was the dominated strategy with higher cost and lower efficacy relative to the Fischer protocol. On sensitivity analysis, reducing the efficacy rate of all FMTs in the Fischer FMT protocol by half and increasing the efficacy of surgery, the Fischer protocol remained the most cost effective strategy (Figure 2). Overall, following the first FMT the Fischer protocol increases the effectiveness above colectomy at a lower cost. Conclusion In this decision analysis, sequential FMT by the Fischer protocol was the most cost-effective treatment strategy for severe complicated CDI relative to standard colectomy or a single FMT. Given limited efficacy data for FMT in the context of severe complicated disease controlled studies are urgently needed to explore this potentially highly cost-effective strategy.
Figure 1: Cost-effectiveness analysis comparing single FMT to total colectomy with ileostomy and the Fischer protocol. Abbreviations: FMT, fecal microbiota transplantation; ICER, incremental cost-effectiveness ratio.
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AGA Abstracts
There was no significant difference at the 95% level among the six cryoprotectant formulations trialled. Conclusion: The choice of cryoprotectant did not make a statistically significant difference to total cell viability in FMT product after lyophilization. However, it is not known whether the lack of a statistically significant difference will translate to equivalent FMT product efficacy in, for example, the treatment of C. difficile infection. In addition, it is possible that the lyophilization process, including the choice of cryoprotectant might affect viability of different groups of FMT bacteria differently, and this bears further study. References: 1. van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. The New England Journal of Medicine. 2013 Jan 31; 368(5): 407-415 Bacterial Indices Following Lyophilization
Figure 2: Two-way sensitivity analysis on probability of death from surgery and incrementally decreasing efficacy of the Fischer protocol. Abbreviations: FMT, fecal microbiota transplantation.
Su1746 Predictors of Failure of Fecal Microbiota Transplantation (FMT) in the Management of Recurrent Clostridium difficile Infection Joseph Dimitry, Ammar H. Keshteli, Dina Kao Background: Fecal microbiota transplantation (FMT) is a safe and effective alternative therapy for patients with recurrent C. diff infection (RCDI), with an overall success rate of 80-90% with one treatment. However, no clinical factors have been identified to predict those who may not respond to FMT. Aim: To identify predictive factors of treatment failure following a single or multiple FMT in RCDI. Methods: This retrospective study included 136 patients who received FMT for RCDI (defined as having at least 3 episodes of CDI) or severe/ complicated CDI, between Oct 2012 and Apr 2015 at the UAH hospital, with at least 3 months of follow-up. Success of FMT was defined as absence of CDI recurrence during the 3 month F/U. Failure was defined as recurrence of diarrhea associated with postive C diff toxin within 3 months of FMT. Those who failed 1 FMT were offered the 2nd FMT during F/U. Patient baseline characteristics, past medical history, medication use (including antibiotic use within 3 months following FMT), CDI classification, severity, and response to therapy, in addition to laboratory data were extracted from in-patient charts and outpatient electronic medical records. Results: Of the 136 patients, 106 (77.9%) were cured following one FMT. Of the 30 patients (22.1%) who failed the first FMT, 25 received a second FMT and 16 were cured. Univariate analysis was performed and the results shown in Table 1. It identified 7 factors to be associated with failure following 1 FMT. Multivariate analysis revealed that inpatient status at the time of FMT (OR 7.4; 95% CI 2.2-24.6, p=0.001), immunosuppresion (OR 4.5; 95% CI 1.3-16.2, p=0.020), and severe/complicated CDI (OR 5.2; 95% CI 1.221.6, p=0.025) were factors most independently associated with failure following 1 FMT. All 9 refractory CDI patients failed the 1st FMT. Antibiotic use within 3 months after FMT, chronic PPI use, duration or episodes of RCDI were not found to be predictors of FMT failure. Conclusion: Inpatient status at the time of FMT, immunosuppression, and severe/ complicated CDI are independent predictor of treatment failure following 1 FMT for CDI. Due to the fact that only a small number of patients failed at least 2 FMT, no predictive factors could be identified for those who failed despite multiple FMT. Interestingly, antibiotic use within 3 months post-FMT or chronic PPI use did not predict FMT failure. Further study with a larger sample size may identify predictors to identify those who may fail despite having at least 2 FMTs. Table 1
Su1745 The Cost-Effectiveness of Competing Strategies for Treating SevereComplicated Clostridium difficile Infection: Comparing Fecal Microbiota Transplantation With Standard Colectomy Liem B. Luong Nguyen, Majdi Osman, Austin L. Chiang, Carolyn Edelstein, Monika Fischer, Ashwin N. Ananthakrishnan, Jessica R. Allegretti, Mark Smith, Zain Kassam Background The clinical and economic burden of severe-complicated Clostridium difficile infection (CDI) is substantial. Colectomy, the current standard of care, carries significant mortality and cost. Recently, evidence suggests a sequential fecal microbiota transplantation (FMT) and antibiotic approach is a highly effective treatment for severe-complicated CDI. However, the cost-effectiveness has not been examined. Accordingly, we aim to compare the cost-effectiveness of FMT versus standard colectomy for treating severe-complicated CDI. Methods We developed a decision analysis model comparing 3 treatment strategies for severe-complicated CDI patients after failing standard intravenous metronidazole as well as oral and rectal vancomycin per guidelines: 1) Sequential FMT by flexible sigmoidoscopy with the need for repeat FMT, to a maximum of 3, and continued vancomycin guided by clinical response and pseudomembranes at endoscopic assessment as described in the literature (Fischer protocol), 2) Single FMT by flexible sigmoidoscopy and 3) Total colectomy and ileostomy. Given the dearth of efficacy data on sequential FMT in severe-complicated CDI, we conducted sensitivity analysis on clinical cure rates of FMT, reducing the expected efficacy by half at each stage of the Fischer protocol. Willingness-to-pay threshold was set at $50,000 per quality-adjusted life-year. All costs were adjusted to 2015 US and analysis was conducted from a societal perspective capturing direct costs at the time of discharge. Results In our model the sequential FMT approach was the most cost-effective strategy to treat severe-complicated CDI compared to a single FMT or standard colectomy (Figure 1). The total cost of the colectomy strategy was 67,422 USD which was significantly higher then the total cost of either FMT strategy (Fischer protocol: 26,700 USD, single FMT: 25,350 USD), each strategy driven by the cost of hospitalization. However, the Fischer protocol was 68% more effective than a single FMT and 56% more effective than colectomy. Colectomy was the dominated strategy with higher cost and lower efficacy relative to the Fischer protocol. On sensitivity analysis, reducing the efficacy rate of all FMTs in the Fischer FMT protocol by half and increasing the efficacy of surgery, the Fischer protocol remained the most cost effective strategy (Figure 2). Overall, following the first FMT the Fischer protocol increases the effectiveness above colectomy at a lower cost. Conclusion In this decision analysis, sequential FMT by the Fischer protocol was the most cost-effective treatment strategy for severe complicated CDI relative to standard colectomy or a single FMT. Given limited efficacy data for FMT in the context of severe complicated disease controlled studies are urgently needed to explore this potentially highly cost-effective strategy.
Figure 1: Cost-effectiveness analysis comparing single FMT to total colectomy with ileostomy and the Fischer protocol. Abbreviations: FMT, fecal microbiota transplantation; ICER, incremental cost-effectiveness ratio.
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