CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA

Pseudomembranous Colitis
Dr.T.V.Rao MD

Dr.T.V.Rao MD

Clostridium difficile
Clostridium difficle (Greek cluster spindle, and Latin difficle difficult), is a species of Gram-positive bacteria of the genus Clostridium that causes diarrhea and other intestinal disease when competing bacteria are wiped out by antibiotics.
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Introduction
Clostridium difficle is a Gram-positive, spore-forming anaerobic bacillus. Most common cause of nosocomial diarrhea. Rate and severity of C. difficle-associated diarrhea (CDAD) increasing. New strain of C.difficile with increased resistance and virulence identified.
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History
1893 first case of pseudomembranous colitis reported as diphtheritic colitis. 1935 Bacillus difficle isolated. 1970s antibiotic-asociated colitis identified. 1978 C. difficle toxins identified in humans. 1979 therapy with Vancomycin or metronidazole 2000 increased incidence and virulence
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Recent Developments
C difficle first described 1935 gram-positive anaerobic bacillus difficult clostridium-difficult to grow in culture Found in stool specimens from healthy neonates leading to misclassification as a commensal organism 1970s: clindamycin colitis pseudomembranous colitis in hospitalized patients 1978: C diffficle recognized as causative organism

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Introduction
Clostridium difficile is a Gram-positive, spore-forming anaerobic bacillus. Most common cause of nosocomial diarrhea. Rate and severity of C. difficile-associated diarrhea (CDAD) increasing. New strain of C.difficile with increased resistance and virulence identified.
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C.difficile
Clostridium difficile, often called C. difficile or "C. diff," is a bacterium that can cause symptoms ranging from diarrhea to lifethreatening inflammation of the colon. Illness from C. difficile most commonly affects older adults in hospitals or in long term care facilities and typically occurs after use of antibiotic medication
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Epidemiology
Present in environment. Hospital is major reservoir. Spores can be recovered from surfaces for months. Spread primarily on hands of HCW. Fecal-oral transmission. Transmission may occur from asymptomatic colonized persons.
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Epidemiology
Colonizes the colon of up to 3% of healthy adults. 15 25% of debilitated and antibiotic-treated hospitalized adults colonized. Toxigenic strains may cause disease in colonized patients. Implicated in approx. 25% of cases of antibiotic- associated diarrhea
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The antibiotics most likely to cause diarrhea

Cephalosporins, such as cefixime (Suprax) and cefpodoxime (Vantin) Clindamycin (Cleocin) Erythromycin (Erythrocin, E.E.S., others) Penicillins, such as amoxicillin (Larotid, Moxatag, others) and ampicillin Quinolones, such as ciprofloxacin (Cipro) and levofloxacin (Levaquin) Tetracyclines, such as doxycycline (Vibramycin, Periostat, others) and minocycline (Minocin, Solodyn, others)
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Other predisposing factors

Previously experienced antibiotic-associated diarrhea while taking an antibiotic medication Are age 65 or older Have had surgery on your intestinal tract Have recently stayed in a hospital or nursing home Have a serious underlying illness affecting your intestines, such as colon cancer or inflammatory bowel disease
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Source of Infection
C. difficle bacteria can be found throughout the environment in soil, air, water, and human and animal feces. A small number of healthy people naturally carry the bacteria in their large intestine. But C. difficle is most common in hospitals and other health care facilities, where a much higher percentage of people carry the bacteria.
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Pathogenesis
Disruption of normal colonic flora Colonisation with C. difficle Production of toxin A +/- B Mucosal injury and inflammation
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Pathogenesis
Microflora of gut:
1012 bacteria/gram 400-500 species colonisation resistance

Transmission faecal/oral
spores

Late log / early stationary phase

toxin production
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Disruption of protective colonic flora (AB or AN)

Colonization with toxigenic C. difficle by fecal-oral transmission Toxin A and B production A/B: Cytoskeletal damage, loss of tight junctions. A: Mucosal injury, inflammation, fluid secretion.

Colitis and Diarrhea

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Clinical features
Mild disease mild abdominal cramping pain. - endoscopic findings of diffuse or patchy, nonspecific colitis. Moderate disease fever, dehydration, nausea, anorexia, malaise, profuse diarrhea, abdominal distention and cramping pain. - moderate leukocytosis, fecal leukocytes. - diffuse, patchy colitis on endoscopy

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Clinical Manifestations
Fulminant colitis:
Rare, 2-3% of patients, esp elderly Serious: ileus, perforation, mega colon, death High fever, chills, marked leukocytosis (>40K) May not have diarrhea if ileus or mega colon Risk of perforation w/ sigmoid/colonoscopy Treatment surgical

Unusual presentations:
Long latency period (1-2months) Absence of antibiotic exposure
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Severe disease
Severe disease usually profuse diarrhea, may be little or no diarrhea. - abdominal pain - fever - volume depletion - marked leukocytosis peritoneal signs - radiologic signs include ileus, dilated colon and edematous colonic mucosa - endoscopic findings of adherent yellow plaques
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Complications of CDAD
Pseudomembranous colitis

Toxic mega colon Perforation of the colon Sepsis Death

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Patients at increased risk for disease

ANTIBIOTIC EXPOSURE Gastrointestinal surgery or manipulation Long length of stay in healthcare setting Infected roommate Co-morbid illnesses Immunosuppression Advanced age Proton-pump inhibitors and H2-blockers?
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Predictors of Severe Disease Leukocytosis > 20,000 Increased creatinine above the baseline
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Traditional list of Antibiotics associated with CDAD

MORE FREQUENT LESS FREQUENT

Cephalosporins (3rd and 4th generation)

Ticarcillin-clavulanate

Ampicillin/Amoxicillin
Clindamycin Other penicillins

Metronidazole
Fluoroquinolones Rifampin

Macrolides
Tetracycline's Trimethoprim-Sulphmethoxazole

5-Fluorouracil
Methotrexate Cyclophosphamide
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DIAGNOSIS
Endoscopy (pseudomembranous colitis) Culture Cell culture cytotoxins test ELISA toxin test PCR toxin gene detection
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Laboratory Diagnosis
Stool culture Latex agglutination to detect antigen in stools Tissue culture assay for cytotoxicity of toxin B Enzyme-linked ImmunoSorbant assay (ELISA) for toxins A and B

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A new strain of C. difficle (NAP-1)

Toxin type III

Unsuppressed production of toxins A and B

Associated with presence of binary toxin. Increased resistance to clindamycin and fluoroquinolones. Potential for increased complications and adverse outcome.
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Management
Enhanced infection control measures. Targeted antibiotic restriction Appropriate antibiotic therapy Adjunctive therapy probiotics, IVIG, toxin binders
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Important supporting approaches

Surgery Avoid ant peristaltic and opiate drugs. Experimental therapy rifaximin, tolevamar, corticosteroids, vaccine, monoclonal antibodies to toxins A and B, non-toxigenic C,difficile
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Antibiotic Therapy
Oral therapy Vancomycin, metronidazole Unable to tolerate oral therapy IV metronidazole, Vancomycin via NG tube or enema. Vancomycin + rifampin Less frequently used Bacitracin, fluidic acid
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Indications for Vancomycin therapy

No response to metronidazole Metronidazole intolerance Pregnancy and child < 10 yrs. Severe/fulminant CDAD
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CDAD continues to be a Important Topic in Clinical Practice Increasing numbers and severity of CDAD. Active surveillance recommended. Early diagnosis and treatment are important for reducing severe outcome. Judicious use of antibiotics may reduce incidence of CDAD Strict infection control practices essential.
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 Programme created by Dr.T.V.Rao MD for Medical and Health Care Professionals in the Developing World
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