bacteria technically 16 Flashcards
Clostridium difficile
Clostridium difficile - Gram +ve, sporing, obligate anaerobe
Range of gastrointestinal disease from antibiotic associated diarrhoea to pseudomembranous colitis and may lead to death
C. difficile infection (CDI) often nosocomial and associated with elderly patients undergoing broad spectrum antibiotic therapy
Incidence and severity of CDI increasing
History of type 027 in the UK
By random, type 027 found in isolation as a single isolate in a small batch from hospital patients from Preston in Jan 1999
Isolates submitted as part of an MSc project of a BMS in Birmingham revealed another single type 027 isolate in April 2002
Not seen again until March 2004 when Rose Gallagher, an ICN from Stoke Mandeville, contacted the ARL about a severe ongoing outbreak of C. difficile. Between Feb-June 2004 they had 150 cases with 12 deaths
Treatment
cessation of antibiotic, if possible
treatment with anti-C. difficile-drugs: vancomycin, metronidazole or fidaxomicin (lower reoccurrence rate, but no difference in initial response rate and expensive-£1300/course)- extended course to prevent recurrence
restoration of normal intestinal flora: “fecal enema” from family member
DRAWBACKS OF ANTIBIOTIC TREATMENT OF C.DIFF
the risk of recurrence, alternative treatment strategies are being investigated
With standard antibiotic treatment, such as vancomycin, there is a 20% risk of recurrence after the primary episode, rising to 40% after the second episode and up to 70% after the third episode.
The evidence suggests that in patients suffering from multiple recurrences the risk of further recurrence after HPI treatment may be a low as 19-6% depending on the number of HPI treatments given.
Treatment for recurring CDI
2nd episode Oral fidaxomicin or vancomycin ≥3 episodes Oral fidaxomicin Vancomycin tapering/pulse dose regimens IV immunoglobulin FMT
Fidax licensing trials- non-Inferior to vanc for initial cure, but superior for reducing recurrence – therefore use in high risk e.g. Conconmitant abx or 1st recurrence
IV immunoglobulin, small case series, no RCTs, use in refractory disease beneficial in 2 thirds of patients. Especially if worsening albumin status
Faecal microbiota transplant for recurrent clostridium difficile
what is it? Blended and filtered suspension of stool from either a:
Related screened donor
Un-related screened donor
Administered to the patient via either: Enema Colonoscopy Nasogastric Nasoduodenal Faecal transplant, fecal microbiota transplant (FMT) or bacteriotherapy
history of FMT
Dong-jin dynasty 4th century, China
Human faecal suspension by mouth for FBD or severe diarrhoea
Described in the Zhou Hou Bei Ji Fang
16th Century Ming dynasty – referred to as ‘yellow soup’
Modern medicine
Eiseman et al. 1958 faecal enema for PC
1990s Prof. Hawkey undertook two FMT procedures in critically ill patients with CDI
FMT service offered in Glasgow, Scotland since 2003
One private clinic in the UK – Taymount Clinic
Well established in USA and Australia
Ding-jin – reported a medical miracle bring patents back from the brink of death. Translates to ‘Handy Therapies for Emergencies’
The treatment remained widely used and reports in the Ming dynasty – various prescriptions fermented faecal solutions, fresh suspensions, dry faeces and infant feces.
Eisman case series of 4 patients
Donors
Un-related healthy donors
Eligibility criteria include:
>18 and <50 years of age
No active health problems
Normal bowel habits
No recent history of diarrhoea or per rectal bleeding
No antibiotics in the preceding 3 months
Written informed consent
Clinical, social and travel risk assessment and microbiology screening
FMT preperation and storage
Fresh stool prepared in dedicated area of containment level 2 R&D
Homogenised with saline containing 10% glycerol
Frozen at -80°C in 50 ml aliquots
6 month expiry
FMT administartion
Administration via nasogastric tube1
Patient nil by mouth morning of treatment
Omeprazole and domperidone given 2 hours before
cost effecitveness of different management stratergies for recurrent CDI
Decision analytic model of reoccurrence following initial treatment comparing 4 1st line treatments:
Metronidazole
Vancomycin
Fidaxomicin
FMT via colonoscope
2 additional reoccurrences in addition to first also modelled
Initial reoccurrence treatment with FMT was most cost effective – incremental cost effectiveness ratio of $17,016 relative to VanC. Fidax and Metro dominated by FMT colonoscope
FMT for CDI in immunocompromised patients
80 cases multi centre – 36 immunosuppressed for IBD
Overall cure rate 78% with repeat FMT 89%
2 deaths 1 aspiration during GA for colonoscopy 1 unrelated
Mild discomfort in 3 patients 1 small mucosal tear during colonoscopy
Very few AE’s – no infection consequences
