Transcript C Difficile In The ICU - Dr Erick Duan

Clostridium difficile infection (CDI) in the ICU
and Clostridium difficile outcomes in the
PROSPECT Main Trial
Erick Duan MD FRCPC
Presented at the CCCTG
Halifax, NS, June 2016
Burden of C. difficile
Most common nosocomial cause of diarrhea
More common nosocomial infection than MRSA
In 2011 (US surveillance data):
• 453,000 cases of CDI
• 29,000 CDI associated deaths
• Increased health care cost
of $1.5 billion USD
Canadian point prevalence study:
In 2002: 0.8% of all admissions
In 2009: 1.2% of all admissions
Leffler NEJM 2015
Taylor Antimicrob Res Inf Cont 2016
And it’s getting worse
Since 2002:
more common
more severe
more refractory to treatment
more recurrent infection
Emergence of hypervirulent strain: 027/BI/NAP1
15-20x toxin production, production of binary toxin
Outbreak in Sherbrooke, PQ (2002)
Increased attributable mortality: 17%
Increased rate of colectomy: 23%
Pepin CMAJ 2005
Clostridium difficle in the ICU
Patients
pre-ICU
Exposures/Interventions
ICU
Prevention
of CDI
Hospital
pts
ICU
pts
colonization
with CD
Diagnosis
of CDI
Hospital
pts with
CDI
Outcomes
severe, complicated
or fulminant CDI
renal failure
shock
colectomy
length of stay
Treatment
of CDI
ICUacquired
CDI
Morbidity
ICU patients
with CDI
pre-ICU
CDI
Mortality
Recurrent
CDI
Treatment of
CDI
Recurrence
Recurrent
CDI
Risk Factors
Incidence
Prevalence
Outbreaks
Prognostic
Factors
Attributable
Morbidity and
Mortality
Attributable
Cost
Burden of C. difficile in ICU
•
Prevalence of ICU-acquired CDI varies greatly
•
80 835 pts in 22 studies
•
Pooled estimate: prevalence of 2% (95%CI 1-2%)
Karanika et al Open Forum
Infectious Diseases 2016
Burden of C. difficile in ICU
Hospital mortality
•
With limitations, there is
some signal that
ICU acquired C. difficile
infection increases
hospital mortality and
hospital LOS
•
Also, increases ICU LOS
with no difference in ICU
mortality
32% 24%
95%CI 26-39% 14-36%
Hospital LOS
50 vs 30 days
Karanika et al Open Forum
Infectious Diseases 2016
Studies of C. difficile in ICU
•
Largely retrospective studies
•
Low event rate
•
Variable definitions of C. difficile infection
•
Severity unknown (and criteria never validated)
•
Complications poorly and inconsistently reported
•
Treatment poorly described
What’s coming down the pipeline for CDI?
What’s coming down the pipeline for CDI?
•
Fecal microbiota transplantation
•
Antibiotics:
•
fidaxomicin, teicoplanin, tigecycline
•
surtomycin, cadazolid
•
IVIG
•
Monoclonal antibodies
•
Vaccine
What’s coming down the pipeline for CDI?
•
Fecal microbiota transplantation
•
Antibiotics:
•
fidaxomicin, teicoplanin, tigecycline
•
surtomycin, cadazolid
•
IVIG
•
Monoclonal antibodies
•
Vaccine
Fecal microbiota transplantation
•
89% cure rate in observational studies
(273 CDI patients)
•
no adverse effects reported
•
compared to
•
18% treatment failures with metronidazole
•
60% chance of recurrence after 2 prior episodes
Kassam Am J Gastroenterol 2013
The trouble with fecal microbiota transplantation
•
typically stool donors are family members
•
stool collected within 6 hours of transplant
•
stool screening process is extensive, and
not standardized
•
reported but not well studied in critically ill patients
•
concern about delaying surgical intervention in
critically ill patients
Frozen as good as fresh
JAMA 2014
JAMA 2016
•
•
232 patients with
recurrent CDI
Cure rates:
• 83.5% frozen
• 85.1% fresh
Coming sometime to
an ICU near you???
Back to
C. difficile
data collection and outcome
adjudication in
PROSPECT
Studies of C. difficile in ICU
•
largely retrospective studies
•
low event rate
•
highly variable definitions of C. difficile infection
•
severity unknown (and criteria never validated)
•
complications poorly and inconsistently reported
•
treatment poorly described
C. difficile Data collection
CRF
C. difficile data collection
C. difficile Adjudication
independent
blind adjudication
consensus on CDI and
CDI related outcomes
randomly allocated
to a pair of adjudicators
ED
consensus
DJC
patients with possible
CDI
JD
consensus
JJ
C. difficile
Adjudication in PROSPECT
C. difficile outcomes in
PROSPECT
Strengths:
•
duplicate adjudication
•
standard definition of CDI (Public Health Ontario)
•
application of multiple severity criteria
•
systematic collection of complications + treatments
•
rich patient baseline and daily data
Limitations:
•
event rate is likely to be low
•
results in a selected RCT population