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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
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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
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. difficileWilcox, 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
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
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 C.difficile spores
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 risksIs 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-65sQuarterly 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