Clostridioides difficile Infection Flashcards
(29 cards)
Problems with Antibacterial Therapy
- Superinfection
- Bacterial
- Fungal
- Alteration of Normal Flora
- Overgrowth of commensal / opportunistic organisms
- Skin / Mucous membranes - Candida
- Candida Vaginitis
- Oral Thrush
- Candida Skin Infections
- Candida in Blood Stream
• GI Tract
• Diarrhea (3.2 - 29%)
• Clostridioides Difficile-Associated Diarrhea (CDAD)
(Pseudomembranous Colitis)
What is Clostridioides difficile?
• Gram-positive anaerobe
• Produces spores and toxins
• Ubiquitous in nature
• Important transmissible nosocomial pathogen
• Spreads primarily through person-to-person transfer
via fecal-oral route and environmental contamination
of surfaces with C. difficile or its spores
______is the primary pathogen
causing antibiotic-associated colitis
• Can result in significant morbidity and mortality
Toxin-producing C. difficile
Epidemiology
Colonization found in ~ 1-3% of healthy people (3-26% of adult
inpatients in acute care hospitals)
• 43% ↑ in incidence of CDI and 189% ↑ in multiple recurrent CDI in the
United States from 2001-2012
▫ 0.63 per 1,000 person years in 2012
• Incidence of healthcare-associated CDI in Canada 4.3 per 10,000
patient-days in 2015 (down from 5.9 in 2009)
C. difficile-associated Diarrhea (CDAD)
• Normal flora in colon is disrupted
• All antibacterials implicated
• Fluoroquinolones, clindamycin, and 3 rd generation
cephalosporins particularly troublesome
• C. difficile attaches to receptors in the gut epithelial cell, proliferate and toxogenic strains may release toxins
(Toxins A and B)
• Toxin B highly pathogenic, essential for virulence
• Toxins cause inflammation and vasoconstriction, leading to the development of pseudomembranous colitis ± necrosis
• Symptoms - diarrhea, fever, abdominal pain, dehydration etc.
Clinical Manifestations of CDAD
• Onset typically 5 -10 days after start of antibacterial therapy, but may occur as long as 10 -12 weeks following antibacterials (index of suspicion)
• Unformed stools (i.e., watery diarrhea that takes the
shape of the container)
• *≥ 3 episodes in 24 hrs may be brief and self-limited orcholera-like with > 20 very liquid stools /day.
- Blood in stools is rare
- Fever (30 - 50%)
- Leukocytosis (50 - 60%) (>15 x 109/L)
- Abdominal pain or cramping (20 - 33%)
- Asymptomatic carriage (possibly protective)
Complications of CDAD
- Dehydration
- Electrolyte disturbances
- Hypoalbuminemia
- Toxic megacolon
- Bowel perforation
- Hypotension
- Renal failure
- Sepsis, septic shock
- Death
Risk Factors for CDAD
• Age – Older adults (> 65 yrs)
• Antimicrobial Tx (>90% occur post-Abx Tx)
- the more abx received, the higher ther risk
- the longer duration of tx, the increased risk
(ceph 2nd gen or higher, fluoroquin high risk) (mod risk with penicillins)
• Hospitalization
• Cancer chemotherapy
• Severe underlying illness
• Manipulation of GIT
• ?H2 Receptor Blockers / Proton Pump Inhibitors
risk management
Infection Prevention and Control
Contact precautions (gloves (Strong, High) and gown (Strong, Moderate))
• Private room and washroom for patient (Strong, Moderate)
• Wash hands with SOAP & WATER (Weak, Low)
• Alcohol rubs do not inhibit/remove spores
• Proper disinfection of surfaces with approved
disinfectants (Strong, Moderate)
• >5,000 ppm Chlorine-containing solutions one of the most effective disinfectants
• Spores may persist for weeks-months on surfaces
MOXIFLOXACIN IS WORST FOR C DIFFICILE (GUT ANAEROBES WIPED OUT AND LEADS TO C DIFF TAKING OVER) > CIPRO > LEVO
Pharmacists CAN have an impact! Antimicrobial stewardship (Good practice)
• Minimize frequency, duration, and number of
antimicrobials prescribed (Strong, Moderate)
• Restriction of
• 3rd generation cephalosporins,
• fluoroquinolones, and
• clindamycin use may be particularly useful
(Strong, Moderate)
• Discontinue inciting antimicrobial therapy as soon as
possible (Strong, Moderate)
Diagnosis of CDAD
• Diarrhea
• ≥ 3 unformed stools (that take the shape of the
container) in ≤ 24 hours
AND ≥1 of the following:
• Positive stool test for C. difficile or its toxins
• Evidence of pseudomembranous colitis
• This criteria should be used for diagnosing initial and recurrent episodes (unless paralytic ileus is present)
start clock when ceftriaxone ends, vanco start
Diagnosis of CDAD
tests
- Stool Culture (72 hrs) – GOLD STANDARD
- Not practical to use routinely
- NAATs such as PCR to detect toxin genes the preferred test (are superior to the enzyme immunoassays for toxins A+B)
- Glutamate dehydrogenase (GDH) is a newer screening test for C. difficile that can be used with 2 or 3-step testing along with testing for toxins A + B (has a high sensitivity, but low specificity)
Approach to CDAD Patient
dont give loperamide, let toxins out
• Discontinue all unnecessary antimicrobials
• Discontinue and avoid antiperistaltics
• Determine if this is an initial or recurrent episode
• Patient care with severe CDAD should include
• Intravenous fluid and electrolyte resuscitation
• Venous thromboembolism prophylaxis
• Oral or enteral feeding should be continued unless patient has a paralytic ileus (fermentable carbohydrates useful for normalizing
the microbiota)
• Use of probiotics not currently recommended (limited data of effectiveness and potential risk of bloodstream infection)
Initial Episode
Criteria
- Symptoms of CDAD
* NO positive C. difficile test results in the last 8 weeks
Recurrent Episode
- Up to 25% of treated CDAD patients have a recurrence
- Recurrences may be due to relapse with original strain or re-infection with new strain
- Criteria:
- Symptoms of CDAD
- ≥ 1 positive C. difficile test result in the last 8 weeks
approach to cdad pt
• If this is an initial episode or the patient’s 1st recurrence,
determine the severity of the episod
- Mild-moderate:
- Leukocytosis (WBC <15.0 x 109 cells/L) AND
- SCr < 130 µmol/L
- Severe:
- Leukocytosis (WBC >15.0 x 109 cells/L) or
- SCr ≥ 130 µmol/L
- Severe, complicated (fulminant):
- Hypotension, shock, ileus, and/or megacolon
Therapeutic Options
Metronidazole
Metronidazole -≥ 85% abs following oral dose • Affects other gut bacteria •AE: Peripheral neuropathy (uncommon), Darkened urine Initial Treatment Response ++ Recurrence Risk ++
Vancomycin
• Negligible abs following oral dose • Affects some gut bacteria • Minimal systemic AE Initial Treatment Response ++ + Recurrence Risk ++
capsules now a regular benefit
Fidaxomicin
• Minimal abs following oral dose • Limited activity against other gut bacteria • Minimal systemic Initial Treatment Response ++ + Recurrence Risk ++
• A new macrocyclic antibacterial
• Not absorbed from GI tract
• Bactericidal against C.difficile
• Prolonged post-antibiotic effect against C. difficile
• Limited activity against normal gut flora
• Preserves Bacteroides groups in fecal flora
• Already seeing elevated MIC to fidaxomicin due to a
mutation in RNA polymerase B
• Expensive
Treatment Recommendations: Initial Episode
mild-mod
severe, uncomp
severe, comp
Mild to moderate (non-severe)
• Vancomycin 125 mg po QID x 10 days (Strong, High), or
• Fidaxomicin 200 mg po BID x 10 days (Strong, High), or
• If above two not available (or cost prohibitive):
▫ Metronidazole 500 mg po TID x 10 days (Weak, High)
Severe, uncomplicated
• Vancomycin 125 mg po QID x 10 days (Strong, High), or
• Fidaxomicin 200 mg po BID x 10 days (Strong, High)
Severe, complicated (fulminant)
• Vancomycin* 500 mg po/NG QID x 10-14 days (Strong, Moderate), AND
• Metronidazole 500 mg IV Q8H (Strong, Moderate)
* If ileus present, consider additional rectal instillation of vancomycin (Weak, Low)
Treatment Recommendations: Recurrence
First Recurrence
Second or Subsequent Recurrence
First Recurrence
• Vancomycin 125 mg po QID x 10 days if metronidazole was used for initial episode (Weak, Low), or
• Prolonged tapered and pulsed vancomycin regimen if a standard regimen was used for initial episode (e.g., 125 mg po QID x 10-14 days, then BID x 7 days, then daily x 7 days, then q48-72h for 2-8 weeks) (Weak, Low), or
• Fidaxomicin 200 mg po BID x 10 days if vancomycin was used for the initial episode (Weak, Moderate
DO NOT USE METRO FOR MORE THAN 2 RECURRENCES
Second or Subsequent Recurrence
• *Vancomycin in a tapered and pulsed regimen (Weak, Low), or
• Vancomycin 125 mg po QID x 10 days, followed by rifaximin 400 mg po TID x 20 days (Weak, Low), or
• Fidaxomicin 200 mg po BID x 10 days (Weak, Low), or
• Fecal microbiota transplantation (Strong, Moderate)
Not Recommended
• Repeat testing (within 7 days) during same episode of
diarrhea (Strong, Moderate)
• Routine identification of asymtomatic carriers (Strong, Moderate)
• Probiotics (limited data to support and may cause blood stream
infection) (No recommendation)
• Adding cholestyramine or rifampin to ↓ risk of recurrence
• Use of antiperistaltic agents
Vancomycin vs Metronidazole
• Systematic review – 4 trials (872 patients) comparing
vancomycin 125 mg QID to metronidazole 250-375 mg QID
• Metronidazole associated with lower sustained symptomatic
cure
Fidaxomicin vs Vancomycin
• Fidaxomicin dose 200mg q12h x10days
• Vancomycin 125mg q6h x 10days
• Rates of clinical cure with fidaxomicin noninferior to
vancomycin (Intention to treat analysis 88.2%vs
85.8%), per-protocol (92.1% vs 89.8%)
• Fewer recurrences with fidaxomicin group 15.4% vs
25.3% P=0.005 (but not followed to 90 days)
• Fidaxomicin significantly lower rate of recurrence of
C.difficile diarrhea with non-North American Pulsed
Field type 1 strain
• Adverse event profile similar
