scholarly journals 670. VRE Clearance in Patients with Recurrent Clostridium difficile Infection Following Treatment with Microbiota-Based Drug RBX2660

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S306-S307
Author(s):  
Heidi Hau ◽  
Sarah Mische ◽  
Sarah Klein ◽  
Ken Blount
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Cohort Analysis ◽  
Intestinal Microbiome ◽  
Phase 2 ◽  
Open Label ◽  
Recurrent Clostridium Difficile Infection ◽  
Gram Staining ◽  
Increased Risk ◽  
Stool Samples

Abstract Background Vancomycin-resistant Enterococcus (VRE) infection is frequently associated with immunocompromised and critically ill patients. VRE carriers are at increased risk for infection due to VRE colonization and they pose a risk as a transmission source. VRE infection and Clostridium difficile infection (CDI) share common risk factors, including disruption of the intestinal microbiome. Thus, therapeutic approaches that decolonize VRE would be valuable. Herein, we report on stool VRE clearance in a cohort analysis from a Phase 2 open-label study of RBX2660, standardized microbiota-based drug, for recurrent CDI. Methods This prospective, multicenter, open-label Phase 2 study enrolled subjects with recurrent CDI. Participants received up to 2 doses of RBX2660 delivered via enema with doses 7 days apart. Patients were requested to voluntarily submit stool samples at baseline and at 7, 30 and 60 days, 6, 12, and 24 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and gram staining. Vancomycin resistance was confirmed via blood agar and etest. Results Stool samples were available for 143 patients. Twenty-one patients were VRE-positive at the first test (baseline or 7 day). Of the 19 VRE-positive patients that provided additional samples at later timepoints, 18 (94.7%) converted to negative as of the last available follow-up (30 or 60 days and 6, 12, or 24 months). The remaining patient remained positive at all follow-ups. Conclusion This cohort analysis of VRE-positive patients within an rCDI population provides additional support that microbiota-based formulations, such as RBX2660, may have additional benefit beyond reducing the recurrence of CDI. Additional study is needed to confirm the role of microbiome restoration on VRE clearance. Disclosures All authors: No reported disclosures

scholarly journals Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Erik R. Dubberke ◽  
Kathleen M. Mullane ◽  
Dale N. Gerding ◽  
Christine H. Lee ◽  
Thomas J. Louie ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Small Sample Size ◽  
Secondary Analysis ◽  
Small Sample ◽  
Vancomycin Resistant Enterococcus ◽  
Recurrent Clostridium Difficile Infection ◽  
Stool Samples ◽  
Vancomycin Resistant

Abstract Background.  Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI). Methods.  A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest. Results.  VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim. Conclusions.  Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.

scholarly journals Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

2018 ◽  
Vol 67 (5) ◽  
pp. 649-656 ◽  
Author(s):  
Dale N Gerding ◽  
Ciaran P Kelly ◽  
Galia Rahav ◽  
Christine Lee ◽  
Erik R Dubberke ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Recurrent Clostridium Difficile Infection ◽  
Increased Risk

scholarly journals Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE)

2018 ◽  
Vol 73 (12) ◽  
pp. 3430-3441 ◽  
Author(s):  
Christoph Högenauer ◽  
Yashwant Mahida ◽  
Andreas Stallmach ◽  
Philippe Marteau ◽  
Grazyna Rydzewska ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Bowel Disease ◽  
Phase Iii ◽  
Open Label ◽  
Increased Risk ◽  
Phase Iiib ◽  
Secondary Endpoints ◽  
Inflammatory Bowel

AbstractObjectivesInflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD.MethodsThe plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591.ResultsMedian Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1–2 h across Days 1, 5 and 10. Cmax ranges were 1.2–154 ng/mL for fidaxomicin and 4.7–555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8–2170 μg/g for fidaxomicin and 0–1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death.ConclusionsMaximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.

scholarly journals Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial

2016 ◽  
Vol 64 (3) ◽  
pp. 265-271 ◽  
Author(s):  
Susy S Hota ◽  
Valerie Sales ◽  
George Tomlinson ◽  
Mary Jane Salpeter ◽  
Allison McGeer ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Controlled Trial ◽  
Fecal Microbiota ◽  
Oral Vancomycin ◽  
Open Label ◽  
Fecal Transplantation ◽  
Recurrent Clostridium Difficile Infection ◽  
Microbiota Analysis ◽  
Vancomycin Treatment

Abstract Background Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI. Methods In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available. Results The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon. Conclusions In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations. Clinical Trials Registration NCT01226992.

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