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38 Cards in this Set
- Front
- Back
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Clostridium difficile
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Spore-forming, Gram-positive bacteria that causes diarrhea and colitis
Identified in the late 1970s Accounts for 15% to 25% of all episodes of antibiotic-associated diarrhea Suspect C. difficile n any patient withdiarrhea who has been hospitalized and has recently received antibiotics |
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since c diff is spore forming what does that mean
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that is goes dormant and when in a sutiable enviroment will grow and replicate
it is very hard to kill and spreads easily it is encapsulated making it very resistant |
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what has happened to the rate of C.diff over the last 6 years
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it has tripled
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Economic Impact of C. difficile
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CDI costs at tertiary care hospital in Missouri
$5,042 attributable inpatient costs per patient over 180 days (53% increase in costs) Massachusetts hospital discharge data CDI principal diagnosis: Mean length of stay, 6.4 days Mean cost per stay, $10,212 >$25 million per annum for CDI management in MA Johns Hopkins Hospital CDI associated with increased LOS of 5.5 days and $6,326 increased cost |
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Risk Factors for CDI
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Recent antibacterial use
Clindamycin, cephalosporins, ampicillin (most notorious) Recent data identify fluoroquinolone use as a prominent risk factor Length of stay in a healthcare facility Increasing age Serious underlying illness Proton pump inhibitors (PPIs) May play a role in predisposing to CDI although conflicting data exist to date |
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CDi
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C. Diff infection
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are the c. diff spores killed in the stomach
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nope
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does everyone get c diff if exposed
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nope
a patient can be hospitalized and have multiple exposures and not get infected they can be asymptomatic with a c. diff colonization and it will go away some of the people exposed do get the c. diff associated disease (this is actually a small subset of those exposed) |
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Antibiotics and Other Drugs Associated with CDI
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common
clindamycin Amp/amox cephlosporins FQ less common chloramphenicol cotrimoxazole macrolides other PENS tetracyclines least common bacitracin cisplatin doxorubicin FU MTX AG vanco rifampin sulfonamides tacrolimus |
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Clostridium difficile Virulence Factors
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2 large protein exotoxins
Toxin A (enterotoxin) Toxin B (cytotoxin) Some strains of C. difficile (BI/NAP1/027) also produce binary toxin Found in ~6% of isolates in U.S. and Europe Structure and function similar to C. perfringens toxin Severity, complications known to be increased in patients infected with strains producing binary toxin |
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toxin a of c. diff
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causes hypersecretions of the cells in the colon resulting in diarrhea
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toxin b of c. diff
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cytotoxin
produces damage to the cells and creates a pseudomembrane |
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is toxin a of c. difff a cytotoxin or enterotoxin
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enterotoxin
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Some strains of C. difficile (BI/NAP1/027) also produce binary toxin
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Found in ~6% of isolates in U.S. and Europe
Structure and function similar to C. perfringens toxin Severity, complications known to be increased in patients infected with strains producing binary toxin the b and a toxins together with this other one YUCK |
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Changing Epidemiology of CDI
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Rates of complications, mortality have increased over recent years
Possibly caused by changes in Antimicrobial use Other drug prescribing practices Infection control practices Emergence of a new strain of C. difficile Increased virulence Antimicrobial resistance Aging of the overall population and, specifically, of the hospital inpatient population (carrying multiple risk factors) |
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Clostridium difficile Infection (CDI)
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Presence of symptoms (usually diarrhea) (because of the enterotoxin)
≥ 3 unformed stools per 24 hours for 2 days Ileus (rarely can develop in the absence of diarrhea in severe disease) Positive stool test for toxigenic C. difficile or its toxins Recent antibacterial use is frequent but not universal |
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when testing for c. diff are you testing for the bacteria or the toxins
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the toxins, because c. diff is hard to culture
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CDI: Clinical Presentation mild
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Lower abdominal cramps
Diarrhea (>3 bowel movements/day) Endoscopy: diffuse or patch, nonspecific colitis |
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CDI: Clinical Presentation moderate
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Fever
Nausea, anorexia, malaise Abdominal distention and cramps Profuse diarrhea Fecal leukocytes Endoscopy: diffuse or patchy, nonspecific colitis |
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CDI: Clinical Presentation
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High fever
Marked leukocytosis (>15,000), albumin <2.5 Severe abdominal pain, distention, ascites Profuse diarrhea (>10 bowel movements/day Fecal leukocytes X-ray: paralytic ileus, dilated colon Hemodynamic instability, renal dysfunction, mental status changes Endoscopy: adherent yellow plaques |
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Diagnosis of CDI
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Clinical suspicion (risk factors with new onset of diarrhea)
Epidemiologic characteristics (older?, in hospital?, underlying comorbidities?) Commonly used laboratory tests Toxin testing Antigen detection assays Stool cultures (rarely) Colonoscopy (more severe cases) Abdominal computed tomography (CT) scan (the last 2 are not all that common or sensitive |
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what is defining physical characteristic of c. diff
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pseudomembranes
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CDI: Treatment
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Isolate patient, contact precautions
Educate healthcare personnel Discontinue offending antibiotic (if possible) Avoid antidiarrheals or opiates Supportive care – fluid replacement (important cause can progress to renal dysfuntion) Confirm diagnosis |
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does alchol work against c. diff
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nope
have to use bleach solutions and good old soap and water |
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Initial Treatment Options CDI
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metronidazole
Oral administration preferred 500 mg PO TID for 10 – 14 days Historical first-line agent Vanco Effective in enteral (oral or rectal) form only 125 mg PO QID for 10 – 14 days (higher doses are not more effective just more expensive) Typically reserved for severe disease patients treated with metronidazole may take longer to respond then those taking vanco |
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is vanco given PO or IV for the treatment of c.diff
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oral because want high concentrations in the lumen of the colon
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Treatment of First Episode of CDI
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Mild CDI
Discontinue offending antibacterial agent Request stool testing but still treat Monitor course of disease Moderate or persisting CDI (or patients who must continue antibacterial therapy) As for mild plus: Oral metronidazole 500 mg TID for 10–14 days or 250 mg QID for 10–14 days Therapy by oral route is ALWAYS preferred Length of therapy: 10-14 days |
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Management of Severe CDI
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Early recognition is critical
Initiate therapy as soon as diagnosis is suspected Manage as for mild CDI plus: Oral vancomycin (125 mg QID x 10 to 14 days) as initial treatment If patient is unable to tolerate oral medication, consider intracolonic vancomycin instillation (by enema) 0.5–1 g vancomycin (IV formulation) in 0.5- to 2-L normal saline via rectal (or Foley) catheter Clamp for 60 minutes Repeat every 4–12 hours |
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Alternate Routes of Vancomycin Delivery for CDI
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Adjunctive treatment (anecdotal, no controlled trials)
Intracolonic instillation1 500 mg IV vancomycin in 100 mL of normal saline via Foley catheter Clamp for 60 minutes Repeat every 6 hours Insertion of long tube into small intestine2 Colonic decompression followed by guidewire positioning of a fenestrated tube and perfusion with a vancomycin solution3 |
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Recurrent CDI
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Recurrent CDI in ~20% of patients after first episode
Antibiotic resistance after treatment not reported Response to the same agent predicted Recurrences may be due to same or new strain Mean time to recurrence: Same strain, 14.5 10 days New strain, 42.5 39 days Treatment: same as first episode, according to disease severity (i.e., second course of metronidazole or vancomycin) |
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if the patient has a recurrent episode of c. diff do you treat with the same antiobiotic or a differnet one than used the first episode
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same
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Multiple Recurrent CDI
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Risk of subsequent episode after first recurrence = 45%
Many empirical regimens advocated Repeated, prolonged courses of metronidazole not recommended Most empirical regimens use vancomycin in tapering or pulsed protocols Combination regimens have also been advocated but few data (eg, vancomycin 125 mg QID + rifampin 600 mg BID x 7 days) |
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why can you not use metronidazole more than 2 times when treating c. diff
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neurotoxicity
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Multiple Recurrent CDAD: Vancomycin Taper Regimen
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125 mg QID x 7 days
125 mg BID x 7 days 125 mg daily x 7 days 125 mg every other day x 7 days 125 mg every 3 days x 7 days every hospital can do this differently |
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Unproven Adjunctive Therapies for Recurrent CDI
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Probiotics
Saccharomyces boulardii Lactobacillus GG May lower further recurrences in some patients when added to and continued after treatment with metronidazole or vancomycin Nitazoxanide Response demonstrated in patients (n=35) who failed prior metronidazole therapy and similar response and recurrence rates when compared with metronidazole for initial therapy (n=110) Rifaximin “chaser” Effective when used for 14 days after vancomycin therapy (n=8) |
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Recurrent CDAD: Fecal Transplantation
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Rationale: restoration of bacterial homeostasis
Preparation of donor specimen Fresh (<6 hours) ~30 g or ~2 cm3 volume Add 50 mL 0.9% normal saline, and homogenize with blender Filter suspension with paper coffee filter Refilter |
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F.B. is a 53 y.o. woman who was recently treated with ceftriaxone and azithromycin for CAP. Several days after completing antibiotic therapy she calls her PCP complaining of new fever, cramping abdominal pain, and severe diarrhea. She is presumptively diagnosed with C. difficile infection. The most appropriate initial treatment for F.B.’s infection would be:
Vancomycin 125 mg PO Q6H Metronidazole 250 mg PO Q6H Clindamycin 300 mg PO Q6H Metronidazole 250 mg IV Q8H |
Metronidazole 250 mg PO Q6H
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F.B. is treated with oral metronidazole for 7 days. However, two weeks later she experiences the same signs/symptoms and appears to have experienced a relapse of C. difficile infection. How should she now be treated?
Metronidazole 250 mg IV Q8H x 10-14 days Vancomycin 250-500 mg PO Q6H x 10-14 days Metronidazole 250-500 mg PO Q6H x 10-14 days Combination of both PO metronidazole + PO vancomycin in x 10-14 days was previously treated with metronidazole |
Metronidazole 250-500 mg PO Q6H x 10-14 days
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