Download Clostridium difficile

C’est difficile…?
Martin Kiernan
Nurse Consultant
Southport and Ormskirk NHS Trust
Vice President, Infection Prevention Society
Clostridium difficile
1935
first described by as bacillus difficilis by Hall and
O’Toole and classified as a commensal
1977
toxin isolated from stool samples produced a
cytopathic effect in cell culture
1978
C. difficile identified as source for toxin and
cause of psuedomembranous colitis
Microbiology
 Gram positive, spore
forming rod shaped
bacillus
 Obligate anaerobe
 Produces 2 major toxins
toxin A and toxin B
both contribute to disease
 Toxins responsible for
manifestation of disease
and marker for
diagnosis
Annual Cases (England)
So why are we where we are?
The authors of the latest 2009 guidelines
considered that ‘it is the failure to implement the
guidance described in the 1994 report that has
contributed to the recent rise’
Noted by the HPA and the HCC in 2006
Financial Burden of C. difficile
Wilcox, Cunniffe et al, JHI; 1996
Cases stay an average of 21.3 days longer
Extra costs
Treatment, Investigations, ‘Hotel costs’
Total identifiable costs over £4,000 per case
2006 costs
My Trust - £400K
NW SHA - 6,946 cases - £28 million
NHS - 55,681 cases - £222 million
NHS lost nearly 1.2 million bed days
Risk factors for disease
Chang and Nelson (2000)
Age > 65 years
Antibiotic therapy, particularly cephalosporins,
clindamycin
Underlying bowel disease
Proton pump inhibitors
PEG feeds
Physical proximity to symptomatic patient
C.difficile, ABx, PPIs
CDAD
Antibiotic x1000
PPI x 1000
60000
50000
40000
30000
20000
10000
0
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Case control study of Community CdI
Wilcox, Mooney et al (2008)
Exposure to Abx in previous 4 weeks
esp. multiple agents
Half had no abx in the previous month
Hospitalisation in previous 6 months
A third had neither hospitalisation not ABx
Contact with infants >2 years old
PPI not significantly more common
C. difficile strains
160 ribotypes of C. difficile
Type 001 most common in UK hospitals,
Community epidemiology differs Type 010 most
common
All sensitive to metronidazole and vancomycin
so far
Epidemiology of C. difficile is changing
Type 106
C. difficile 027
Hyper-toxin producer
18 base pair deletion ? Red herring
16-20 times more toxin produced
Toxin produced earlier in the disease process
Overwhelming of immune response
Presence of binary toxin
? Red herring
Diagnosis of C.difficile
Clinical diagnosis
sigmoidoscopy
radiology
Toxin isolation
cytotoxin assay 92% sensitivity & specificity
expensive and lengthy incubation required
culture less efficient
rapid immunoassay (less expensive, quick)
Smell…
Clinical manifestations of C.difficile
Asymptomatic carriage
2% healthy adults
16-35% recently treated with antibiotics
important reservoir in medical facilities
shed organisms, contaminate environment
carriage not reduced by treatment with
metronidazole or vancomycin
Clinical manifestations of C.difficile
Antibiotic colitis
presents as diarrhoea, lower abdominal pain
starts during or shortly after antibiotics commence (a
few days) but may present much later (1-2 months)
systemic symptoms often absent
examination often normal including sigmiodoscopy
toxins in stool
Clinical manifestations of C.difficile
Psuedomembranous colitis
symptoms more marked, bloody stools
characteristic yellow plaques 2-10mm
intervening mucosa mild inflammation
plaques may conjoin
rectum and sigmoid most common
may progress to fulminant colitis
Fulminating Disease
 Five Alerts
Abdominal distension and tenderness
High (very high) WCC
( can be 40-50 x109/l)
Raised CRP/ drop in Hb
Non response
To oral metronidazole/vancomycin
Low albumin
 all these features could denote the presence of Toxic
Mega Colon - IMMEDIATE senior review, abdominal
Xray and surgical referral
Management of C.difficile
Treatment
resuscitation
stop causative antibiotic (if possible)
antibiotics
restore normal gut flora
Surgery
Mortality from surgery 25-100%
Low Serum Albumin a good predictor of certain
death (<25g/L) or a fall by 11g/L at the onset of
infection
Saccharomyces boulardii
Produces a protease that inhibits effect of
toxins A and B in human colonic mucosa
colonisation by 72 hours 107-108 cfu
cleared when therapy discontinued
not absorbed
Expensive
Different preparations have differing activity
Other options?
Brewers yeast
Saccharomyces cerevisae
less expensive than S.boulardii
but distinct and not equivalent
Faeces from related donors
Given as enema or via Nasogastric Tube
Not very acceptable to staff or patients
Immunoglobulin
Transmission
Faecal-oral route
Environment becomes contaminated by spores
Hands become contaminated by spores
Vulnerable patients acquire spores after contact with
contaminated staff and the environment
And then they eat them..
What is Critical?
Prevent environmental contamination
Consider faecal containment if liquid stool
Rapid isolation of the patient
Simple things
Pulling back the sheets
Commode cleaning
Side room with toilet
No exposed food
Careful with that bedding
C.difficile spores
 Environment
floors
toilets
bedpans
bedding
mops
scales
 Health Care
professionals
hands
rings
stethoscopes
faecal carriage rare
Am J Epidemiology 1988
127:1289-94
Am J Med 1981;70:906
Just how important IS the environment?
Samore et al
presence on hands correlates with density of
environmental contamination (AmJ Med 1996)
0-25%sites +
0% hands +
26-50% +
8% hands +
>50% +
36% hands +
Fawley (Epid Infect 2001)
incidence correlates significantly with level of
environmental contamination
Isolation Wards
They work
They also free up isolation capacity elsewhere
in the organisation
They ensure consistency of care for all
patients, whose primary diagnosis should now
be considered to be the infection
They are not permanent
They do allow you to get the situation back under
control and draw breath
Cross-infection risks
Is it only the symptomatic patient?
One paper recently published in Clinical
Infectious Diseases in October 06 says not
56% of skin tests were positive for C. difficile
in the asymptomatic patient
Spores present on the skin can be effectively
transmitted to HCW hands and the environment
Hands must be washed with soap and water
after dealing with faecal matter for every
patient
Efficacy of Alcohol Hand Sanitizers
Provide an overall 3-4 log10 (99.9-99.99%)
reduction in most bacterial and viral pathogens
with a contact time of 15 seconds
NOT C. difficile spores
NOT Norovirus
Norovirus are reduced by only 1-2 log10
(90-99%) with a 30 second contact time
C. difficile in the over-65s
Quarterly Cases - England, 2006-8
C’est tres difficile
Increasing elderly population
Average age of inpatients up 1.5 years each year
Acute beds falling in numbers
Creates a filtered inpatient population
Expectation to treat
Have sympathy for the poor house officer
The ‘old man’s friend’ is now his greatest
enemy