C Diff Flashcards
C Difficile is defined as greater than or equal 3 unformed stools in 24 hours with:
A stool test positive for C diff toxins or detection of toxin C diff
OR
Colonoscopic or histopathologic findings revealing pseudomembranous colitis.
-Pseudomembranous colitis – severe inflammation of the inner lining of the bowel
Healthcare facility-onset (HO) CDI
laboratory identified event collected >3 days after admission to the facility
Community-onset, healthcare facility-associated (CO-HCFA) CDI
CDI that occurs within 28 days after discharge from health-care facility
Community-associated (CA) CDI
onset of symptoms within 48 hours of admission to hospital or more than 12 weeks after discharge
C-Diff can exist in spore and vegetative forms
Spore form – resistant to heat, acid, and antibiotic
Vegetative form – active, fully functional, toxin producing and become susceptible to killing antimicrobial agents
Spore C Diff
resistant to heat, acid, and antibiotic
Vegetative form
active, fully functional, toxin producing and become susceptible to killing antimicrobial agents
Produces two potent exotoxins, toxin A and toxin B
Toxin A – causes inflammation leading to interstitial fluid secretion and mucosal injury
Toxin B – 10 times more potent than toxin A
Pathogenesis of C Diff
- ) Antibiotic use
- ) Disruption of colonic microflora
- ) C diff exposure and colonization
- ) Release of toxin A and toxin B
- ) Mucosal injury and inflammation
Clinical Manifestation of C-Diff
new onset of ≥ 3 unformed stools in 24 hrs (May be associated with mucus or occult blood)
Low grade fever Nausea Unexplained leukocytosis Hypovolemia Lactic acidosis Hypoalbuminemia Pseudomembranous colitis
Risk Factors
Mainly divided into 3 categories: advanced age, underlying illness and medical history, and immunosuppression
Significant risk factors: antibiotic use and age.
All antibiotics can be associated with CDI
Age: one study demonstrated that the risk of contracting CDI during an outbreak was 10x as high among persons older than 65 years of age as among younger inpatients.
Very common medications that Associated to C-Diff
**Clindamycin Ampicillin Amoxicillin Cephalosporins **Fluroquinolones
Somewhat common medications associated with C-Diff
Other Penicillins Sulfonamides Trimethoprim Bactrim Macrolides
Ticket to test
Lab Test Recommendations
Submit stool samples only from patients with unexplained and new onset > 3 unformed stool in 24 hrs
DO NOT submit stool samples on patients who have been receiving laxatives
Lab Test Recommendations
Nucleic acid amplification test (NAAT) alone OR with stool toxin test as part of a multiple step algorithm (GDH + toxin, GDH + toxin, arbitrated by NAAT, or NAAT + toxin) rather than toxin test alone
Glutamate dehydrogenase (GDH)
Sensitivity - High
Specificity - Low
Availability - Widely
Toxin A + B enzyme immunoassay (EIA)
Sensitivity - Low
Specificity - High
Availability - Widely
Nucleic acid amplification test (NAAT)
Sensitivity - High
Specificity - High
Availability - Widely
Multistep algorithm for C-Diff Diagnosis
Perform 2 rapid diagnostic stool tests in a symptomatic patient
Concordant results –> Final results
Discordant results –> Perform a third test on discordant samples –> Check results of the test –> Final results
Detailed Diagnostic
- ) Perform Enzyme Immunoassay for Glutamate Dehydrogenase in stool sample
- ) Perform Enzyme Immunoassay for Toxin A and B in stool samples
- ) Perform Enzyme Immunoassay for Glutamate Dehydrogenase in stool sample
- ) Perform Enzyme Immunoassay for Toxin A and B in stool samples
If GDH+a / toxin+ testing consistent with C-Diff
If GDH+ / Toxin-a OR If GDH- / Toxin+a perform PCR for tcbdB Gene (if + consistent with C-Diff / if - not consistent with c-diff)
GDH - / Toxin -1 not consistent with C-Diff
Initial episode, non severe C-Diff diagnosis
Leukocytosis with a white blood cell count of ≤15,000 cells/mL
AND
Serum creatinine level <1.5 mg/dL
Initial episode, severe C-Diff diagnosis
Leukocytosis with a white blood cell count ≥15,000 cells/mL
OR
Serum creatinine level >1.5 mg/dL
Initial episode, fulminant
clinical presentation:
Hypotension or shock
Ileus
Toxic megacolon
First recurrence
Reappearance of symptoms AND positive assay within 2-8 weeks after treatment has been stopped
Second or subsequent recurrence
Reappearance of symptoms and positive assay within 2-8 weeks after treatment for the first recurrence has been stopped
CDI recurrence defined by
resolution of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms and positive assay within 2-8 weeks after treatment has been stopped
Prevention of C-Diff
Improve antibiotic Prescribing Use best test for accurate results Rapidly identify Wear gloves and gowns Hand sanitizer does not kill C-Diff Use EPA approved agents (spores)
Treatment Medications
Metronidazole Vancomycin Fidaxomycin Fecal microbiota Bezlotuxumab
Treatment of Non-severe C-Diff
Vancomycin 125 mg PO four times a day for 10 days
Fidaxomicin 200 mg PO twice a day for 10 days
Metronidazole 500 mg PO three times a day for 10 days
Treatment of Severe C-Diff
Vancomycin 125 mg PO four days a week for 10 days
Fidaxomicin 200 mg PO twice a day for 10 days
Treatment of fulminant C-Diff
Vancomycin 500 mg PO or via nasogastric tube four times a day
If ileus, consider adding vancomycin 500 mg in approximately 100 mL normal saline per rectum Q6H as a retention enema.
Present ileus, add metronidazole 500 mg IV Q8H with oral or rectal vancomycin
Treatment of first recurrence C-Diff
If metronidazole was used for the initial episode, administer vancomycin 125 mg PO QID for 10 days
If vancomycin was used for initial episode, administer fidaxomicin 200 mg BID for 10 days
Prolonged tapered and pulsed vancomycin regimen
Second or subsequent recurrence treatment
Vancomycin in tapered and pulsed regimen
Vancomycin 125 mg PO QID for 10 days followed by rifaximin 400 mg PO TID daily for 20 days
Fidaxomicin 200 PO BID for 10 days
Fecal microbiota transplantation (FMT)
Metronidazole MOA and AE
After diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms
Metallic taste
“Furry” tongue
Nausea
Disulfiram reaction (vomiting, nausea, flushing, tachycardia, and dyspnea) when taken in combination with alcohol
Vancomycin - MOA
Bactericidal
Binds to the D-Ala-D-Ala terminal of the nascent peptidoglycan pentapeptide side chain and inhibits transglycosylation, interfering with cross-linking and preventing the elongation of peptidoglycan chain
Vancomycin Oral AE:
Hypokalemia (13%)
Abdominal Pain (15%)
Nausea (17%)
Vancomycin hydrochloride (Firvanq®)
Oral solution
Indicated in adults and pediatric patients less than 18 years of age for:
C.difficile-associated diarrhea
Enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains)
Vancomycin hydrochloride (Firvanq®)
Oral solution Dose for C.difficile – associated diarrhea:
Adults: 125 mg PO 4 times daily for 10 days
Pediatric (<18 years of age): 40 mg/kg in 3 or 4 divided doses for 7-10 days
Fecal microbiota transplantation
Reintroduction of normal bacteria via donor feces will correct the imbalance of colon microbiota; thus restoring phylogenetic richness and colonization resistance
Bezlotuxumab (Zinplava) is a human monoclonal antibody that binds to C.difficile toxin B
Indication:
Indicated to reduce recurrence of CDI in patients >18 years of age who are receiving antibacterial drug treatment of CDI and are at high risk for CDI recurrence
Should only be used in conjunction with antibacterial drug treatment of CDI
