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Thera VII > 30 Clostridium difficile Infection Tran > Flashcards

30 Clostridium difficile Infection Tran Flashcards

1
Q

What is Clostridium difficile?

A

Gram (+) bacillus, obligate anaerobic, spore-forming, toxigenic, grows best at 37 C. CDI - toxin mediated intestinal disease

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2
Q

What are the toxins released by C. difficile?

A

Toxin A: enterotoxin, intestinal fluid secretion, inflammation, causes diarrhea. Toxin B: cytotoxin, 10x more potent, mucosa cell death

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3
Q

What are the two forms that C. difficile can take?

A

Vegetative (growth) form. Spores (dormant) form

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4
Q

What is the Vegetative (growth) Form of C. difficile?

A

Found in gut, survive < 24hr in environment, susceptible to gastric acid, antibiotics

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5
Q

What is the Spores (dormant) Form of C. difficile?

A

Survive years in environment, resistant to gastric acid, heat, radiation, chemicals, germinate into vegetative bacteria in gut

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6
Q

What are the characteristics of the Hypervirulent strain of C. difficile?

A

Increased rate/production of Toxin A & B from tcdC gene dysfunction. Binary toxin, possible synergism with Toxin A and B in causing severe colitis

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7
Q

What are the two routes of pathogenesis for CDI (C. difficile infection)?

A

Person to person contact. Fecal-oral contamination

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8
Q

What are the key steps in the pathogenesis of CDI?

A

1) Ingestion of spore, vegetative cells. 2) Colonization with toxigenic C. difficile. 3) Disruption of normal colonic flora. 4) Toxin mediated cellular damage. 5) Tissue edema, inflammation

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9
Q

What are the risk factors for CDI?

A

Antibiotic exposure (most important modifiable risk factor). Advanced age (5x higher aged > 65yo). Hospitalization or long term care facility (LTC). Acid-suppressing agents (2x increased risk for CDI pts receiving PPI). GI surgery or GI procedures

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10
Q

Which antibiotics MORE frequently cause CDI?

A

Clindamycin, 2nd/3rd Gen CEPHs, B-Lactams, FQ, Macrolides, TCN

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11
Q

What are some antibiotics that less frequently cause CDI?

A

AG, Vancomycin, Rifampin, Chloramphenicol

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12
Q

What is the definition of CDI?

A

3+ unformed stools in 24 hrs and stool (+) C. difficile toxins or colonoscopic/histopathologic demonstrating PMC

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13
Q

What is Mild-Moderate CDI?

A

Non-bloody, watery diarrhea (5-10 stools/day). Fever, abdominal cramp. WBC < 15,000, serum creatinine < 1.5x premorbid level

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14
Q

What is Severe CDI (Including PMC)?

A

Blood in stool, profuse watery diarrhea (> 10 stools/day). High fever (102-104), severe abdominal pain and tenderness. WBC > 15,000, serum creatinine > 1.5x premorbid level (WBC > 20,000, SCr > 2 associated with 25% mortality 30-day)

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15
Q

What are the complications associated with Severe CDI?

A

Hypotension or shock, bowel perforation, megacolon, ileus

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16
Q

What is the last stage in the progression of CDI?

A

Toxic megacolon (~30-60% mortality)

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17
Q

When should CDI testing be done?

A

Should be performed only on diarrheal (unformed) stool (testing of asymptomatic patients not recommended)

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18
Q

What is the Testing Strategy to Diagnose CDI?

A

Stool culture is most sensitive, but not practical (turnaround time 2-3 days; can’t determine if toxins being released). Cell cytotoxicity assay is highly sensitive but labor intensive. Ezyme immunoassay (EIA) for Toxin A & B, often used in CONJUNCTION with another test. PCR is rapid, sensitive and specific (expensive)

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19
Q

What is NAAT like for CDI?

A

Stand alone test (to date PCR is most sensitive and specific). Positive = Positive for Toxigenic C. difficile. Negative = Negative for Toxigenic C. difficile

20
Q

What are the General Treatment Principles for CDI?

A

Asymptomatic disease does not require treatment. Discontinue offending antibiotic if possible. Avoid antiperistaltic agents. Supportive care (hydration, electrolyte replacement). Diarrhea may be self-resolving (mild disease). Surgical intervention (increase mortality with lactate > 5, WBC > 20,000). Antibiotics only kill or inhibit vegetative form (actively growing): spores represent survival strategy

21
Q

What are the treatment options for CDI for a First Episode?

A

Metronidazole. Vancomycin

22
Q

What are the treatment options for Recurrent CDI?

A

Metronidazole. Vancomycin. Fidaxomicin. Rifaximin

23
Q

What are the alternative/adjuvant strategies for CDI?

A

IVIG. Cholestyramine

24
Q

What is the supportive clinical data for mild or moderate CDI?

A

WBC < 15,000. SCr < 1.5x premorbid

25
Q

What is the treatment regimen for mild or moderate CDI?

A

Metronidazole 500mg PO TID 10-14 days

26
Q

What is the supportive clinical data for Severe CDI?

A

WBC > 15,000. SCr > 1.5x premorbid

27
Q

What is the treatment regimen for Severe CDI?

A

Vancomycin 125mg PO QID 10-14 days

28
Q

What is the supportive clinical data for Severe, Complicated CDI?

A

Hypotension or shock, ileus, megacolon

29
Q

What is the treatment regimen for Severe, Complicated CDI?

A

Vancomycin 500mg PO QID + Metronidazole 500mg IV Q8h

30
Q

What are some general characteristics of Metronidazole?

A

Synthetic nitroimidazole, cidal against anaerobic bacteria, protozoa, ameba. Disrupt DNA structure –> cell death. Fecal concentration reflects secretion from colon (9.3 watery stool, 1.2 formed stool)

31
Q

What are the ADRs associated with Metronidazole?

A

GI, metallic taste, neurotoxicity (peripheral and central) with long term use

32
Q

What are the general characteristics of Vancomycin?

A

Large glycopeptide, bacteriostatic against C. difficile; inhibits cross-linking of peptidoglycan in cell wall of Gram (+). Poorly absorbed, high fecal concentration (64-880)

33
Q

What are the ADRs associated with Vancomycin?

A

Systemic absorption at higher doses +/- inflammation, emergence of VRE

34
Q

What is the difference in Metronidazole and Vancomycin in CDI treatment?

A

Pretty similar in mild infection. Vancomycin superior in severe infection

35
Q

What is 1st recurrence like for CDI?

A

Up to 25% after treatment of 1st episode of CDI. Similar risk between vancomycin or metronidazole. Per IDSA guideline, either metronidazole or vancomycin can be used

36
Q

What is 2+ recurrence like for CDI?

A

50-65% after 2+ episodes. Metronidazole is discouraged after 2 courses of therapy (risk of peripheral neuropathy d/t cumulative neurotoxicity). Pulse or taper vancomycin PO (Taper: 125mg PO BID x 7d, then QD x7d, then Q2-3 day x2-8 weeks. Pulse: 125, 250, or 500mg Q3d x4-6 weeks)

37
Q

What is Fidaxomicin (Dificid)?

A

1st in new class of macrocyclic, highly selective/cidal against C. difficile, minimal effect on normal flora. High fecal concentration (639-2710). Inhibits spore formation, unlike vanco or metro. VERY expensive

38
Q

How is Fidaxomicin dosed?

A

200mg PO BID x10 days

39
Q

How do the studies compare Fidaxomicin vs. Vanco?

A

Fidaxomicin is only slightly better than vanco

40
Q

What is Rifaximin like for CDI treatment?

A

Non-absorbable analog of rifampin. Binds RNA polymerase, block RNA transcription. 200mg PO TID. FDA approved for traveler’s diarrhea and hepatic encephalopathy

41
Q

What is Nitazoxanide like for CDI treatment?

A

Approved for Cryptosporidium and giardia, exact MOA unclear, also studied as antiviral. 500mg PO BID. Similar response/relapse rate compared to vanco

42
Q

What is Tinidazole like for CDI treatment?

A

Nitroimidazole similar to metronidazole, approved for amebiasis, giardia, trichomoniasis. 500mg PO BID

43
Q

What is IVIG like for CDI treatment?

A

Provides passive immunotherapy. Option in severe, complicated CDI at 150-400mg/kg/dose

44
Q

What is Cholestyramine like for CDI treatment?

A

Polymer resin, exchanges Cl ions for toxin forming non-absorbable complex. Generally safe but effectiveness unproven. 2-4g PO 2-3x/day, separate 2-3hr from vanco dose

45
Q

What are Probiotics like for CDI treatment?

A

Repopulation of normal flora. Cases of bacteremia, fungemia, by translocation from GI tract. Insufficient data recommended for routine treatment of recurrent CDI

46
Q

What is Monoclonal Antibody treatment like for CDI?

A

CDI recurrence associated with lower concern anti-toxin A & B. MAB against Toxin A & B reduced CDI recurrence compared to vanco and metronidazole. No difference in length of stay

47
Q

What can be done for Infection Control & Prevention of CDI?

A

Hand hygiene with SOAP AND WATER (alcohol doesn’t work). 1:10 household bleach works. Decrease duration of exposure and number of antibiotics. Acid suppressive therapy may increase risk of CDI

Thera VII (37 decks)

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