Clostridium Difficile Infection

Transcription

1 This has been a year of annus horribilis Nov 24, 1992 HRM Queen Elizabeth Clearly Most Patient s feel this way as well #1 cause of diarrhea in health care setting 500,000 cases per year 3.2 billion dollars in excess cost ICU admissions - 10% Colectomy - 2.5% Mortality range of 2-16% : 10-30,000 deaths/year Increasing cause of community acquired diarrhea 5% The beginning Diptheroid Colitis 22 yo with hemmorrhagic diarrhea 10 days after gastric surgery.. psuedomembrane Finney J Johns Hopkins Hosp Bull 1893:4;

2 What s in a name? Bacillus Difficilis Hall JC, Otoole E Am J Dis Child 1935:45; Intestinal Flora in new born Infants The long journey 1950 s: 8-10% patients on antibiotics.diarrhea 3% had psuedomembranes? Staphylococcus aureus enterocolitis 1970 s : Golden Syrian Hamsters Clostridium Sordelli anti toxin 2

3 The Cause Patient with diarrhea & pseudomembranes was found to have a toxin neutralized by clostridium sordelli anti-toxin. She responded to oral vancomycin Her stool cultured for clostridium difficile Rifkin GD, Fekety FR et al Lancet 1977:2; Where can we find Clostridium Difficile? New Born Infants 60-70% JH Batts,, J Pediatrics 1980;92: Healthy Adults 3-8% S Nakamura, Micro Immuno 1981;25: House cats/dogs 20-40% SP Borriello,, J Clin Path 1983;36: Farm animals 40-50% Jhun, Emerg Inf Dis 2008;14:

4 C. Difficile can also be found in Food Bratswurst 6/10 60% Ground beef 13/26 50% Ground turkey 4/9 44% Ground pork 3/7 43% Chorizo 3/10 30% JG Songer, Emerg Inf Dis 2009, 15: Clostridium difficile Infection C. difficile can also be found on vegetables Mixed veggies 2.3 Mixed green salad 7.5% N Saif, J Med Microb 1996;45: M Bakri, Emerg Inf Dis 2009;15: If it is everywhere how come we all don t get sick? Normal Colonic Flora 1200 different species of bacteria 10,000,000,000,000 bacteria / gram of feces Renders us resistant to colonization by clostridium difficile KH Wilson, Infect Immunity, 1986;54:

5 Pathogenesis Hospitalized Ingest Spores Survives Gastric Acidity Germinates in the Small Bowel Colonizes the Large Bowel Antibiotics IgG to Toxin A (+) IgG to Toxin A (-) Colonization Infection s Alteration of normal colonic flora Antibiotics 96% had exposure within prior 14 days Enemas RR 3.26 Reglan RR 3.06 Tube Feeds 18% vs11% Antacid/ Anti-ulcer meds Chemotherapy GI surgery MM Olson Inf Cont Hosp Epid;1994:15; McFarland Jour Inf Dis, 1990;160: VG Loo NEJM, 2005;353(23); Role of the Hospital N=428, Period=11 months, Location=1medical ward Cultures Rectal swabs for Cdiff Culture (+) on Admission 7%. 59% Asymptomatic Culture (+) after 48 hours 21%.. 63% Asymptomatic Environmental carriage Bedrail 39% Commode 38% Floor 36% Call Button : 30% Mcfarland LV NEJM:1989;320;

6 Role of the Hospital Private vs Semi-private Room N=299 : Patients with negative Cdifficle culture on admission 92 were exposed to room mate with cdifficile RR 2.23 acquiring cdifficile in 48 hours 20/23 isolates were identical to cohort 61% of room mates were asymptomatic Private Room Semi private Room 7/100 admissions 17/100 admissions Mcfarland LV, NEJM:1989;320: Role of the Hospital Health Care Personnel N=35 Health Care Workers Method: Cultured hands before & after contact with CDI patients No gloves 20/35 acquired C.difficile 14/16 nondisinfectant soap 1/7 - disinfectant soap Wore gloves 0/4 acquired C.difficile Mcafarland LV NEJM 1989;320; The long steady march forward Incidence rates per population 1980 s 20/100, s 30/100, /100, > 84/100,000 **Age >65 867/100,000 Kelly CP NEJM 2010;359:

7 Annual Incidence (per 100,000 Population) of C. difficile Infection in Sherbrooke, Quebec, Kelly C, LaMont J. N Engl J Med 2008;359: The Role of the Bacteria? J strain : R- Clindamycin NAP1/ > strain The Role of the Bacteria? 078 strain N=385 Not hospitalized in previous year Younger age 50 year : median age Female Less exposure to antibiotics Less exposure to antacid Khanna S Am J Gastro 2012:107:89 Chitris AS, JAMA Int Med 2013;273:1359 7

8 The Role of the Bacteria NAP1/027 strain Exponentially higher production of Toxins A & B x toxin levels Lack of tcd R gene : up-regulates toxin production Resistance to Fluoroquinolones Production of 3 rd toxin binary toxin 8

9 Classic Profuse watery or mucoid green, foul smelling stool,crampy, abdominal pain Severe Similar diarrhea fever > 38.3C, albumin < 2.5 gm, leucocytosis(>15k), hypotension on presentation, renal failure with creatinine > 1.5 x baseline, Age > 65 years. No diarrhea, abdominal distention and severe pain. Atypical Unexplained leucocytosis in the hospital (>15k 58% had cdiff) Treatment Metronidazole vs Vancomycin N=150, MTZ 250 mg q6h vs Vancomycin 125 mg q6h Rate of Cure MTZ VAN P Mild 90% 98% 0.36 Severe 84% 97% 0.02 Rate of Relapse Mild 8% 5% 0.67 Severe 21% 10% 0.30 Zar, FA CID;2007:45:302-7 Treatment Fidaxomycin(dificid) vs Vancomycin N=548 Fidaxomycin Vancomycin Cure Rate 88.2% 85.8% Relapse rate 15.4% 25.3% p Louie TJ, NEJM, 2011 sept 15 9

10 Treatment Antibiotics Metronidazole mg oral or iv q8 hours Oral Vancomycin mg oral q 6 hours Rectal Vancomycin 500 mg in 100 ml saline q 6 hours Rifaximin 400 mg po q 8 hours Dificid 200 mg po q 12 hours Nitazoxanide Tigecycline Why does it keep coming back? Antibiotics kill the clostridium difficile bacteria. It does not repopulate normal bacteria in colon It does not restore local immunity in colon Rationale for fecal transplant It restores the normal bowel flora thus preventing growth of C.difficile. By restoring normal bowel flora, you improve colon immune function to deal with C.difficile. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Eiseman B, Silen W.Surgery 1958;44:

11 Duodenal Infusion of Donor Feces for Recurrent Clostridium Difficile University of Amsterdam Groups Infusion of donor feces via nasoduodenal tube Vancomycin 500 mg for 14 days Vancomycin + bowel Lavage Follow up of 10 weeks Fecal transplant 13/16 (81%) Vancomycin alone 4/13 (31%) Vanco +Lavage 3/13 (23%) NEJM Jan 16, 2013 Els Van Nood Summary Results of Mean Laboratory Values at 72 hours post FMT N=20 FMT via enema (9),colonoscopy(9),ng tube (2) 15/20 had dramatic improvement at 72 hours and symptom fee at 6 weeks Pre FMT Post FMT p-value WBC(cells/mm3) <0.001 HCO3(mmol/L) <0.001 Creatinine cl (ml/min) Weinberg A, Zachariah J Diversity of fecal microbiota & fecal transplant Simpson s Reciprocal Index Pretransplant 57 Posttransplant 179 Donor 172 NEJM, Jan 16, 2013 Els van Nood 11

12 How do we prevent transmission? Contact precautions Private rooms Gloves Gowns Hand hygiene Wash with water & disinfectant soap for 30 seconds Environmental Cleaning Hypochlorite solutions (1:10)/5000pt/million Bleach (1pt/10 pt water) Conclusions Strains will vary from decade to decade. Reoccurrence of disease is likely determined by host factors. Judicious use of antibiotics is the most critical element. Environmental decontamination is crucial. Always, always wash hands with disinfectant soap & water for 30 seconds. 12