Clostridium Difficile Colitis. Anton Sharapov, PGY 5

Transcription

1 Clostridium Difficile Colitis Anton Sharapov, PGY 5

2 Outline Case Introduction Diagnosis Treatment New risk factor

3 Clostridium sp. 60 species, most saprophytic four major problems intestinal deep tissue supporative skin/soft tissue infection bacteremia

4 Clostridium GM +, obligate anaerobe oral-fecal route of transmission spore forming difficile grows slowly, difficult to culture

5 Discovered in 1935, Bartlett normal flora newborns PMC more prevalent in 1970s St. Aureus is blamed intitially

6 Nosocomial exposure to bugs/spores susceptibility of the host loss of protective colonic flora the right kind of bug toxin secreting

7 Basic epidemiology Superinfection occurs during abx treatment of other conditions 3 mln cases of diarrhea in US/year prevalent nosocomial infection up to 20% of inpatients test positive only 1/3 of these develop sxs

8 mild, self limiting rapidly progressive septic suspicion is the first step in therapy rule out other causes of diarrhea

9 Implicated culprits Antibiotics clindamycin many others even vanco and metro in NA, most common 1st gen cephalo Change in bacterial flora of the colon proliferation of toxin producing strains

10 C.Diff complicates course of IBD and AIDS 4-12% of all causes of diarrhoe in AIDS associated with antineoplastic agents methotrexate

11 Mechanism of Toxicity Toxin A enterotoxin elicit an acute inflammatory response in animals. Toxin B cytotoxin cause release of proinflammatory mucosal cytokines

12 Pathological picture Macro: inflammatory exudate on the mucosal surface yellow to gray pseudomembranes intervening areas of normal mucosa Micro: plaques of inflammatory cells, disrupted crypts, and cellular debris volcanos of inflammatory infiltrate that erupt from

13 Presentation Watery diarrhea voluminous, +/-blood, smell spectrum of sxs/signs fever leukocytosis abdominal pain tenderness

14 Natural History Highly variable sxs begin 4-10/7 into abx treatment 25% begin after abx d d/c d prophylaxis/single dose have been implicated prompt resolution when offenders d/c d

15 Natural History cont d protracted 8 weeks diarrhoe lytes/albumin disbalance toxic megacolon/perforation

16 Key to diagnosis Temporal relation of sxs and abx sometimes weeks-months prior Harrisons - within 4 weeks diarrhea 72 after admission to the hospital typical clinical picture tests

17 Tests Cytotoxic Immunocytochemistry Latex agglutination Other

18 Lab ID Cytotoxic enzyme assay (toxin B) gold-standard not 100% sens/spec takes time h no correlation btw level and severity Rapid enzyme immuno assay based assay (usually toxin A) less accurate fast

19 Tests cont d The latex agglutination test detects the presence of glutamate dehydrogenase produced by C difficile sensitivity of this test is 48-59%,specificity is 95-96% not recommended

20 fecal leukocytes present 50% of time imaging

21 Antibiotic associated diarrhoe - endoscopic view 1- normal mucosa 2- mild erythema/oedema 3- granular/friable/hemorragic mucosa 4 - pseudomembranes

22 Toxin recovery and stage C. Diff toxin recovery depends on stage 15-75% in three categories 95% in pseudomembranous other factors may be important

23 Carriers CF patients (50%) Pts < 2 yoa (7 60%) Pts > 2 yoa (<4%) Healthy adults given antibiotics (50%) Adults hospitalized >4/52 (50%) Elderly in chronic care 21% Elderly in acute care 14%

24 Normal Colonic Flora

25 Do we treat/eradicate carriers? Treatment of asymptomatic carriers is not recommended

26 Testing guidelines Test only diarrheal stool that which assumes the shape of the container. Do not perform tests of cure toxin tests can remain positive for long periods after treatment.) Test only patients who are older than one year due to the high carriage rate in infants. Test diarrhea that develops after three days of hospitalization for C. difficile sxs

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29 Treatment of 1st episode Stop offending abx start oral vancomycin or flagyl IV flagyl (not vanco) works as well 10-14/7 course improvement in 4/7 complete resolution in 2/52

30 Antibiotics of choice Metronidazole (Flagyl) mg PO tid or qid X days Vancomycin HCl (Vancocin, Vancoled) 125 mg PO qid X days

31 Adjuncts avoid antidiarrheal agents cholestyramine & colestipol anion exchange resins effectve for mild cases only bind toxin (and abx) Prevention is key

32 Recurrent 20-25% experience recurrence within 1 week - 2 months usually more severe repeat course metro/vanco

33 Why recurrence? Unclear mechanisms not related to bacterial resistance to standard antimicrobial therapies breakdown of the normal flora barrier of the colon after antibiotic treatment repeated use of antibiotics disrupts normal colonic bacteria predisposes to recurrent C difficile infection

34 Vancomycin and metronidazole kill the vegetative form of C. difficile do not kill the spores can germinate and eventually produce toxins can exist in the local environment for up to 6 months

35 5 Risk factors previous C. difficile diarrhea onset of disease in spring exposure to additional antibiotics for treatment of other infections infection with immunoblot type 1 or type 2 strains of C difficile female gender

36 goal initial treatment to eliminate the bacteria and vegetative spores. Tapering the dose of vancomycin or metronidazole over 4 to 6 weeks has been shown to be effective. works to kill viable C difficile bacteria destroys the spores while enabling the normal colonic flora to re-grow

37 Regimen Tapering oral antibiotic dose Vancomycin, 125 mg qid X 7 days, then bid X week, then OD X week, then alternate days X week, then q3d X 2 weeks

38 Alternative Anion-binding resin Cholestyramine (LoCHOLEST, Prevalite, Questran), 4 g PO tid or qid X 14 days plus... Vancomycin, mg PO qid X 14 days

39 Other combinations of antibiotics Vancomycin, mg PO qid X 14 days plus Rifampin, mg PO bid X 14 days or Bacitracin, 25,000 U PO qid X 14 days

40 Teicoplanin a glycopeptide antibiotic similar to vancomycin 4 times more potent than vancomycin in vitro no more effective than vancomycin (as demonstrated in a prospective study) expensive may lead to the development of resistant enterococcal strains

41 Probiotics repopulate or restore colonic bacteria as an adjunct to antibiotic therapy Saccharomyces boulardii nonpathogenic yeast releases a protein that interferes with the binding of toxin A to its receptor In a randomized placebo-controlled trial S boulardii plus vancomycin or metronidazole reduced the relapse rate by 50%

42 probiotic lactobacillus GG effective against relapsing C difficile infection it inhibits proliferation of the bacteria A combination of pooled human IgG antibodies and antitoxin A shown to increase serum antibody levels and help resolve the infection

43 Bacteriotherapy taken to the limit % of patients will have multiple relapses despite repeated, prolonged courses of antibiotics fecal enemas has been tried The first published account 1958 by Eiseman limited by the risk of hepatitis and retrovirus transmission galon of GOLYTELY washout 500 ml stool/ns suspension following

44 Human probiotic infusions (HPI) Matter of semantics several reports hey, this S#!^ works! It s all in Flora Power restores the balance short chain fatty acids

45 No response to treatment? Rethink diagnosis scope/cytotoxic assay

46 Prevention Don t you be a phomite hands stethoscopes, sphygmomanometers, or commodes

47 Toxic megacolon 3% of all cases elderly, debilitated, comorbid High mortality rate emergent surgery % Limited proctoscopy minimal air insufflation, may be a useful diagnostic tool

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49 Montreal adventure Cohort study study of PPI and incidence of C.Diff infection PPI increase rates of infection 6.8% in abx 9.3% in abx plus PPI H2 are still the good guys

50 Case-control study not ideal match up cases had more comorbidities PPIs shown RR 2.1 for development of diarrhea no more risk if >1 abx/high risk abx Single use ABX: quinolone, vanco, 2 & 3 gen ceph RR spread crosses 1.0 cefazolin RR 9.2 ( )

51 Did PPIs affect mortality? Difficult to assess mortality RR prolonged use of PPI (especially >6 months) increases RR female gender a risk factor

52 Effects of PPI Elevated gastrin levels trophic effect on colonic/gastrics mucosa decreased gastric acidity inadequate sterilization of ingested bugs colonization of upper GI unclear effect on colon

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55 Sharapova Rules!!!

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