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• 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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• 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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• 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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• 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
• 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.
Dr.T.V.Rao MD 6
• 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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• 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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• 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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• Disruption of normal colonic flora • Colonisation with C. difficle • Production of toxin A +/- B • Mucosal injury and inflammation
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• Microflora of gut:
– 1012 bacteria/gram – 400-500 species – colonisation resistance
• Transmission faecal/oral
• 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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• 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
• 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 – 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)
Clindamycin Other penicillins
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• Endoscopy (pseudomembranous colitis) • Culture • Cell culture cytotoxins test • ELISA toxin test • PCR toxin gene detection
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• 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
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.
• 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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• 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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