C L O S T R I D I U M D I F I C I L E A S S O C I AT E D D I A R R - - PowerPoint PPT Presentation

C L O S T R I D I U M D I F I C I L E A S S O C I AT E D D I A R R H E A

Janel Liane Bernardo Cala PGY1 Pharmacy Resident 8.29.17

CLOSTRIDIUM DIFICILE INFECTION

• Clostridium dificile- gram (+) ; anaerobic; spore forming rod
• CDI = diarrhea + positive stool sample +/- pseudomembranous colitis*

– Onset: median of 2-3 days – Hx of antimicrobial/antineoplastic tx within 8 wks in a majority of patients – Transmission: oral-fecal route; fomites (commodes, rectal thermometer) – Watery diarrhea, lower abdominal pain, systemic symptoms (fever, anorexia, nausea, malaise, leukocytosis, ↑CRP, ↓Alb, occult colonic bleeding) – Severely ill patients may have little or no diarrhea due to toxic megacolon and paralytic ileus (loss of colonic muscular tone)

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

CDI: RISK FACTORS

• Advanced Age (>/= 65 years)
• Exposure to antimicrobial agents
• Cancer chemotherapy
• Duration of hospitalization
• Degree of exposure to other patients with CDI
• Acid- suppressing medications: PPI’s, H2RA’s

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

Poutanen et al. (2004). Clostridium dificile Associated Diarrhea in Adults. Canadian Medical Association Journal. Retrieved from http://www.cmaj.ca/content/171/1/51.full.pdf+html.

CDI: VIRULENCE FACTORS

Toxins A and B – Trigger the attraction and adhesion of PMNs  inflammation of the mucosal lining and cellular necrosis, as well as increased peristalsis and capillary permeability, leading to diarrhea and colitis – Induce production of TNF-a and proinflammatory IL, contributing to the associated inflammatory response and pseudomembrane formation – Toxin B produces more potent damage to colonic mucosa compared to toxin A

Poutanen et al. (2004). Clostridium dificile Associated Diarrhea in Adults. Canadian Medical Association Journal. Retrieved from http://www.cmaj.ca/content/171/1/51.full.pdf+html.

NAP1/BI/027 Hypervirulent strain has been linked to several outbreaks of severe disease in North America and Europe 16 fold increase in toxin A production and 23 fold increase in toxin B production

CDI: PREVALENCE

• Asymptomatic colonization

– 7% – 26% (adult in acute care facilities) – 5% - 7% (elderly in LTCF) – Patients who were recently colonized with C. difficile and who have a high serum antibody response to C. difficile toxins were usually protected against diarrhea and remained asymptomatic carriers (Kyne et al, 2001)

• Clostridium difficile Associated Diarrhea (CDAD)
• Accounts for 20% - 30% of antibiotic associated diarrhea
• Most commonly recognized cause of infectious diarrhea in healthcare

settings

• Not a reportable condition- few surveillance data
• Incidence rates range from 3.8 to 9.5 cases per 10 000 patient- days

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

CDI: DIAGNOSIS

• Test Sample: diarrheal (unformed) stool, unless (+) ileus
• Asymptomatic patients- testing not recommended
• IDSA and SHEA proposed a two-step testing process for CDI:

 Initial Screen : GDH (Glutamate Dehydrogenase) test

• GDH - constitutive enzyme produced in large amounts by all strains of CDI
• Very sensitive, but not very specific for toxigenic C. dificile
• Detects if C. dificile is present but not if bacteria is producing toxins

 Confirmatory tests:

• Cell cytotoxicity test
• T
• xigenic stool culture
• PCR assays

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

CDI: DIAGNOSIS

 CONFIRMATORY TESTS:

• Cell Cytotoxicity test
• Tissue culture to detect C. difficile toxin
• Looks for effects of cytotoxin in human cells
• time consuming- takes 24- 48 hrs for results
• excellent specificity; decreased sensitivity
• Toxigenic Stool Culture
• Growing C. difficile in culture
• Excellent specificity & sensitivity; GOLD STANDARD
• Takes 2- 3 days for results
• Polymerase Chain Reaction (PCR)
• Rapid, sensitive, expensive

Poutanen et al. (2004). Clostridium dificile Associated Diarrhea in Adults. Canadian Medical Association Journal. Retrieved from http://www.cmaj.ca/content/171/1/51.full.pdf+html.

CDI: PREVENTION

• Contact precautions, gloves and gowns
• Hand washing- antimicrobial soap + water
• Environmental disinfection- chlorine-containing agents; sporicidal agents
• Antimicrobial Use: choice, duration, switching IV to PO

– Decrease (11.5 cases/mo to 3.33 cases/mo) of CDI incidence after decreasing use

• f Clindamycin (Climo et al)
• Restrict use of clindamycin and cephalosporins (except for surgical ppx)
• Probiotics- limited data

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

CLINICAL DEFINITION SUPPORTIVE CLINICAL DATA RECOMMENDED TREATMENT ADVERSE EFFECTS INITIAL EPISODE (MILD TO MODERATE) WBC <15K SCr < 1.5 x premorbid level Metronidazole 500mg PO TID Neurotoxicity- seizures, neuropathy, encephalopathy Metallic Taste INITIAL EPISODE (SEVERE) WBC >15K SCr > 1.5 x premorbid level Vancomycin 125mg PO QID Nephrotoxicity Ototoxicity Infusion reaction (Redman Syndrome) INITIAL EPISODE (SEVERE, COMPLICATED) Hypotension, shock, ileus Vancomycin 500mg PO/NGT QID + Metronidazole 500mg IV TID Complete ileus: Vancomycin Retention Enema Vancomycin 500 mg / 100 ml NS Q6H Same as initial episode SECOND RECURRENCE Vancomycin tapered/pulsed regimen

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

ANTIBIOTIC COST PER DOSE REGIMEN COST PER 10 DAY REGIMEN Metronidazole 500 mg $ 0.73 500 mg TID $ 22 Vancomycin 125 mg pills $ 17 125 mg QID $ 680 Vancomycin 125 mg IV (compounded for oral) $ 2.50 - $10 125 mg QID $ 100 - $ 400 Fidaxomicin 200 mg $ 140 200 mg BID $ 2800

Surawicx, CM et al. (2013). Guidelines for Diagnosis, Treatment, and Prevention of Clostridium dificile Infections. American College of Gastroenterology. Retrieved from https://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/

Fidaxomycin - binds to and prevents movement of the "switch regions" of bacterial RNA polymerase

• recurrent CDAD; failure from Metronidazole/

Vancomycin

• 200 mg PO BID x 10 days
• no renal adjustment needed
• high cost
• minimal systemic absorption; narrow spectrum of activity
• ADV: N/V/ abdominal pain

CDI: TREATMENT

• DC causative antimicrobial ASAP
• Supportive tx : hydration, correction of electrolyte imbalance
• Antiperistaltic agents: not recommended; precipitate toxic megacolon
• Colectomy: for severely ill patients (toxic megacolon)

↑ perioperative mortality: Serum lactate >5 mmol/L; WBC ~50 000

• 1st Recurrence: same as initial episode
• 2nd recurrence:

Vanc pulse dosing; avoid metronidazole (cumulative neurotoxicity)

• Fecal transplant: NGT/ enema; consider after 3 recurrences
• IVIG: used with success in a small number of patients with fulminant disease

Cohen, SH et al. (2010). Clinical Practice Guidelines for Clostridium dificile Infection in Adults. Infectious Disease Society of America. Retrieved from https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf

CDI: RECURRENCE

• Risk Factors:

– Age > 65 – Increased severity of underlying disease – Exposure to additional antibiotics after treatment – Compromised immunity; Low serum antibody response to C. dificile toxin

• Multiple relapses: Rifaximin; Rifampin +

Vanc; Rifampin + Colestipol/ Cholestyramine

• Circulating antitoxin antibodies are protective against primary and recurrent CDI

(Leav et al, 2010)

Poutanen et al. (2004). Clostridium dificile Associated Diarrhea in Adults. Canadian Medical Association Journal. Retrieved from http://www.cmaj.ca/content/171/1/51.full.pdf+html.