HA Convention 2018 Initial Experience of Faecal Microbiota Transplantation for the Treatment of Clostridium difficile Infection in Hong Kong Rashid NS Lui MBChB (CUHK), MRCP (UK), FHKCP Division of Gastroenterology and Hepatology Department of Medicine and Therapeutics Prince of Wales Hospital
C. difficile is a leading cause of healthcare associated infection globally Most common microbial cause C. difficile infections in adults, Hong Kong 2006 2014 associated infections in US hospitals of healthcare- Costs up to US $4.8 billion each year in excess healthcare costs for acute care facilities alone > 80 percent of deaths associated with C. difficile occur among Americans aged >= 65 years increased significantly by χ2 test forwith trend) of(p<0.001 5 patients 1 out a healthcare-associated C. difficile infection experienced a recurrence www.cdc.gov, accessed March 2018 Ho J et al. Emerg Infect Dis. 2017 Oct;23(10):1671 1679
Treatment Algorithm for C. difficile Infection Initial Episode Non fulminant Fulminant Vancomycin Fidaxomicin (Metronidazole PO) Vancomycin + Metronidazole IV Surgery Recurrent 1st & 2nd Multiple Vancomycin (tapered and pulsed) Fidaxomicin Faecal Microbiota Transplantation (FMT) Adapted from CPG for Clostridium difficile Infection in Adults and Children: 2017 update by IDSA/SHEA
Ge H. Zhou Hou Bei Ji Fang. Circa 4 th Century AD van Nood E et al. N Engl J Med. 2013 Jan 31;368(5):407 15
Establishing a pilot FMT service for treating C. difficile infection in PWH No established FMT centre in HK Pilot FMT service Retrospective review Unmet need / service gap for the treatment of CDI 26 patients treated since 2013 Assess safety, efficacy and feasibility No alternatives for difficult totreat CDI dependent on antibiotics
Fresh Stools Frozen Stools
Baseline Characteristics Mean age, years (IQR) 64.3 (52.0 80.8) Gender, male, n (%) 16 (61.5%) Smoker or ex smoker, n (%) 6 (23.1%) Drinker or ex drinker, n (%) 2 (7.7%) Bedridden/Chairbound status, n (%) 11 (42.3%) Hospitalization within 3 months or long term care facility resident, n (%) Comorbidities (%) Hypertension Diabetes Liver disease Renal impairment Inflammatory bowel disease Colorectal cancer Pseudo obstruction Stroke Gout COPD Parkinson s Schizophrenia Ankylosing spondylitis 14 (53.8%) 6 (23.1%) 2 (7.7%) 3 (11.5%) 4 (15.4) 2 (7.7%) 2 (7.7%) 3 (11.5%) 2 (7.7%)
Results Route of administration, n (%) Feeding tube OGD Colonoscopy 17 (65.4%) 5 (19.2%) 4 (15.4%) Resolution of diarrhea, n(%) 19 (73.1%) Need of repeat FMT, n (%) 4 (15.4%)
Adverse Events Death at 30 days, n (%) 0 (0%) Serious adverse events, n (%) 0 (0%) Side effects, n(%) Abdominal pain, discomfort or bloating GI bleeding Coffee ground aspirate Anemia Fast atrial fibrillation Lower limb ischemia Refeeding syndrome Hypoalbuminemia Hypokalemia 3 (11.5%)
Stool Biobank Close collaboration with the Faculty of Medicine, Chinese University of Hong Kong Established under the GutMicrobe @ CU Medicine research programme in November 2016 First of its kind in Hong Kong to support clinical services and research
Donor Screening Demographics Age 18 45 years of age Pre screening interview Diet Non vegetarian Travel history Drugs antibiotics, probiotics, recreational, psychoactive etc. Atopy and autoimmune disease Malignancy Metabolic syndrome GI surgery resulting in altered anatomy GI disease including IBD, IBS, chronic diarrhoea, polyposis Neurodevelopmental disorder Blood borne disease Contraindication to blood donation Physical examination BMI 18 23
Stringent Donor Criteria Disease Hepatitis A/E Hepatitis B Hepatitis C Human immunodeficiency virus Investigations Anti HAV IgM, Anti HEV IgM HBsAg, anti HBc Anti HCV Anti HIV Human T lymphotropic virus Anti HTLV 1 Nororivus, rotavirus Syphilis Bacterial (Escherichia coli O157, Shigella, Salmonella, Vibrio, Campylobacter) Multidrug resistant organisms (MDRA, CRE, VRE, MRSA) Helicobacter pylori Clostridium difficile Parasite (Clonorchis sinensis, Crytosporidium parvum, Giardia lamblia, Entamoeba histolytica, Microsporidia, Cyclospora, isospora) RNA PCR VDRL Culture Culture Anti H. pylori IgG or stool Ag GDH Microscopy
Subjects flowchart Baseline visit check eligibility criteria & current illnesses #collect demographic details *collect stool collect <30ml blood and urine Screening test visit check eligibility criteria & current illnesses collect stool and blood for laboratory test Month 3 visit same as baseline visit Month 4 visit same as screening test visit Month 0 Month 1 Month 3 Month 4 Window period Window period One cycle of donor screening and stool collection Start another new cycle CUHK Faculty of Medicine Stool Bank_Protocol_20160115 (version 1.0)
FMT Multidisciplinary Team Nursing Research Team Infectious Disease GI Physician Stool Biobank Endoscopy Centre Microbiology
Establishing a dedicated FMT centre at PWH Knowledge Transfer Education Training Accreditation Research FMT Registry Cost effectiveness Analysis Novel Applications Territory wide Consultations and Referrals FMT Service Long Term Safety Monitoring FMT Centre
Therapeutic Potential of FMT Graft versus host disease MDRO colonization Smits LP et al. Gastroenterology. 2013 Nov;145(5):946 53
Conclusion First case series using faecal microbiota transplantation (FMT) to treat Clostridium difficile infection (CDI) in Hong Kong Delivery of FMT was shown to be safe, efficacious and feasible Large unmet need and service gap for patients with difficult to treat CDI Only hospital in Hong Kong that provides this therapeutic option Huge potential for future service and research development The establishment of a dedicated FMT centre in Hong Kong should be considered
Acknowledgements Prof. Francis KL Chan, Prof. Justin CY Wu, Prof. Siew C Ng, Dr. Louis HS Lau, Ms. Kitty CY Cheung. Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, CUHK Prof. Paul KS Chan, Ms. Miu ling Chin. Stool Biobank and Department of Microbiology, CUHK Ms. MY Wong, Endoscopy Centre, PWH Ms. WY Lo and Ms. Myron Lai, Wards 11A and 11B, PWH