Flashcards in 30 Clostridium difficile Infection Tran Deck (47):
What is Clostridium difficile?
Gram (+) bacillus, obligate anaerobic, spore-forming, toxigenic, grows best at 37 C. CDI - toxin mediated intestinal disease
What are the toxins released by C. difficile?
Toxin A: enterotoxin, intestinal fluid secretion, inflammation, causes diarrhea. Toxin B: cytotoxin, 10x more potent, mucosa cell death
What are the two forms that C. difficile can take?
Vegetative (growth) form. Spores (dormant) form
What is the Vegetative (growth) Form of C. difficile?
Found in gut, survive < 24hr in environment, susceptible to gastric acid, antibiotics
What is the Spores (dormant) Form of C. difficile?
Survive years in environment, resistant to gastric acid, heat, radiation, chemicals, germinate into vegetative bacteria in gut
What are the characteristics of the Hypervirulent strain of C. difficile?
Increased rate/production of Toxin A & B from tcdC gene dysfunction. Binary toxin, possible synergism with Toxin A and B in causing severe colitis
What are the two routes of pathogenesis for CDI (C. difficile infection)?
Person to person contact. Fecal-oral contamination
What are the key steps in the pathogenesis of CDI?
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
What are the risk factors for CDI?
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
Which antibiotics MORE frequently cause CDI?
Clindamycin, 2nd/3rd Gen CEPHs, B-Lactams, FQ, Macrolides, TCN
What are some antibiotics that less frequently cause CDI?
AG, Vancomycin, Rifampin, Chloramphenicol
What is the definition of CDI?
3+ unformed stools in 24 hrs and stool (+) C. difficile toxins or colonoscopic/histopathologic demonstrating PMC
What is Mild-Moderate CDI?
Non-bloody, watery diarrhea (5-10 stools/day). Fever, abdominal cramp. WBC < 15,000, serum creatinine < 1.5x premorbid level
What is Severe CDI (Including PMC)?
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)
What are the complications associated with Severe CDI?
Hypotension or shock, bowel perforation, megacolon, ileus
What is the last stage in the progression of CDI?
Toxic megacolon (~30-60% mortality)
When should CDI testing be done?
Should be performed only on diarrheal (unformed) stool (testing of asymptomatic patients not recommended)
What is the Testing Strategy to Diagnose CDI?
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)
What is NAAT like for CDI?
Stand alone test (to date PCR is most sensitive and specific). Positive = Positive for Toxigenic C. difficile. Negative = Negative for Toxigenic C. difficile
What are the General Treatment Principles for CDI?
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
What are the treatment options for CDI for a First Episode?
What are the treatment options for Recurrent CDI?
Metronidazole. Vancomycin. Fidaxomicin. Rifaximin
What are the alternative/adjuvant strategies for CDI?
What is the supportive clinical data for mild or moderate CDI?
WBC < 15,000. SCr < 1.5x premorbid
What is the treatment regimen for mild or moderate CDI?
Metronidazole 500mg PO TID 10-14 days
What is the supportive clinical data for Severe CDI?
WBC > 15,000. SCr > 1.5x premorbid
What is the treatment regimen for Severe CDI?
Vancomycin 125mg PO QID 10-14 days
What is the supportive clinical data for Severe, Complicated CDI?
Hypotension or shock, ileus, megacolon
What is the treatment regimen for Severe, Complicated CDI?
Vancomycin 500mg PO QID + Metronidazole 500mg IV Q8h
What are some general characteristics of Metronidazole?
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)
What are the ADRs associated with Metronidazole?
GI, metallic taste, neurotoxicity (peripheral and central) with long term use
What are the general characteristics of Vancomycin?
Large glycopeptide, bacteriostatic against C. difficile; inhibits cross-linking of peptidoglycan in cell wall of Gram (+). Poorly absorbed, high fecal concentration (64-880)
What are the ADRs associated with Vancomycin?
Systemic absorption at higher doses +/- inflammation, emergence of VRE
What is the difference in Metronidazole and Vancomycin in CDI treatment?
Pretty similar in mild infection. Vancomycin superior in severe infection
What is 1st recurrence like for CDI?
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
What is 2+ recurrence like for CDI?
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)
What is Fidaxomicin (Dificid)?
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
How is Fidaxomicin dosed?
200mg PO BID x10 days
How do the studies compare Fidaxomicin vs. Vanco?
Fidaxomicin is only slightly better than vanco
What is Rifaximin like for CDI treatment?
Non-absorbable analog of rifampin. Binds RNA polymerase, block RNA transcription. 200mg PO TID. FDA approved for traveler's diarrhea and hepatic encephalopathy
What is Nitazoxanide like for CDI treatment?
Approved for Cryptosporidium and giardia, exact MOA unclear, also studied as antiviral. 500mg PO BID. Similar response/relapse rate compared to vanco
What is Tinidazole like for CDI treatment?
Nitroimidazole similar to metronidazole, approved for amebiasis, giardia, trichomoniasis. 500mg PO BID
What is IVIG like for CDI treatment?
Provides passive immunotherapy. Option in severe, complicated CDI at 150-400mg/kg/dose
What is Cholestyramine like for CDI treatment?
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
What are Probiotics like for CDI treatment?
Repopulation of normal flora. Cases of bacteremia, fungemia, by translocation from GI tract. Insufficient data recommended for routine treatment of recurrent CDI
What is Monoclonal Antibody treatment like for CDI?
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