C. Diff Microbiology and Management Flashcards

1
Q

C Diff microbiology
Aerobic/anaerobic
Spore forming/non-spore forming
Gram-pos/Gram neg
Shape?

A

Anaerobic
Spore forming
Gram-pos
Shape? Bacillus

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2
Q

What are C. Diff spores resistant to? What are vegetative cells resistant to?

A

Resistant to
- oxygen
- heat
- acidity
- drying
- alcohol
- Antimicrobials

Vegetative cells
- most are killed in the stomach

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3
Q

How is C. diff transmitted? What can kill C. Diff

A

Hospitals: fecal-oral route

Must use soap and water to kill C.diff.
- Alcohol-based hand sanitizer is not sufficient

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4
Q

What is the pathophysiology of C diff after most vegetative cells are killed in the stomach and spores remain? (3)

A
  1. Spores germinate into vegetative cells when exposed to bile acids in SI and multiply
  2. Once in colon, bacteria adheres to epithelium and produce toxins
  3. Toxins bind receptors in the colon, resulting in fluid secretion, mucosal damage, and inflammation
    - Toxin A: unable to cause disease alone
    (disrupts neuron function with toxin B)
    - Toxin B: induces leukocytes to release inflammatory mediators
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5
Q

What are symptoms of C. diff?

A
  • watery diarrhea
  • painful cramps
  • colitis
  • pseudomembrane formation
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6
Q

What is the main deciding factor if C. Diff is ingested that will cause infection? (4)

A
  • Underlying health status
  • immune response
  • size of inoculum
  • virulence of the strain

Disruption of normal flora

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7
Q

Explain asymptomatic shedders

A
  • Have high serum antibody to toxin A
  • mild underlying disease (pretty healthy otherwise)
  • Can still spread it in environments
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8
Q

What are the 4 major risk factors of c.diff from strongest to least strongest

A
  1. Antimicrobial exposure
  2. Hospital/LTC home resident
  3. Age 65+
  4. on acid-supression therapy (PPI> h2ra)
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9
Q

Why is antimicrobial exposure the strongest risk factor? How long does the risk last for?

A

When C.diff arrives in colon, it has to compete with the normal flora
- lack of a robust normal flora, due to collateral damage from antimicrobials

Greatest risk during antibiotic use and 1 month later (highest risk right after antibiotic use)

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10
Q

What are the highest risk antimicrobials? (5)

A
  • fluoroquinolones
  • clindamycin
  • blactam + blactam inhibitor combo
  • broad spectrum cephalosporins (3rd gen +)
  • carbapenems
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11
Q

What are low risk antimicrobials for CDI

A
  • Tetracyclines
  • Aminoglycosides
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12
Q

Does absence of antimicrobial use rule out C.diff

A

No

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13
Q

Why is age a risk factor?

A
  • more likely to be in environments with C. diff
  • more likely to receive antibiotics (due to underlying issues)
  • gradual deterioration of immune system
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14
Q

What are other minor risk factors of C. diff (4)

A
  • enteral feeding (g-tube)
  • chemotherapy
  • GI surgery
  • Severe underlying illness
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15
Q

Can CDI occur in patients with no identifiable risk factors?

A

Yes

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16
Q

What is the most important of C. Diff symptom? what is the requirement (4)? What are other symptoms you can experience (4)? What is unusual (2)?

A
  1. Diarrhea (3+ times/24 hrs)
    - must be liquid
    - may have mucus
    - profoundly and uniquely foul-smelling
  2. Leukocytosis
    - (40+ x 10^3)
  3. Have some degree of dehydration
    - inc Scr, decreased urine output
  4. Pseudomembranes

Other symptoms
- lower abdominal pain, tenderness, cramping, or low-grade fever

Unusual
- melena (tar-looking)
- BRPR (bright red)

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17
Q

Explain pesudomembranes

A

Pathognomonic for CDI
- can be diagnosed on its own

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18
Q

What are the 3 stages of complications of CDI

A
  1. ileus
  2. toxic megacolon
  3. Bowel perforation –> colectomy or death
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19
Q

What occurs during ileus? What are symptoms you can see

A

Intestinal paralysis due to inflammation of the smooth muscle layer
- opioids can cause this

Symptoms
- abdominal distension (things build)
- diarrhea SLOWS DOWN or stops
- can develop vomiting (no where else to go)

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20
Q

What occurs during Toxic Megacolon?

A
  • very dilated colon with pseudomembranes (systemic toxicity)
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21
Q

Explain enzyme immunoassay (EIA) test for glutamate dehydrogenase (GDH) antigen
- What does it test for?
- What are limitations?
Highly sensitive/specificity

A

What does it test for?
- C. diff

What are limitations?
- does not differentiate between toxic and non-toxic strains

Highly sensitive (negatives are usually negatives)

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22
Q

Explain EIA test for toxin B
What does it test for?
What are limitations?
Highly sensitive/specificity

A

What does it test for?
- if toxin present

What are limitations?
- risk for false negatives if not enough toxins are present

Highly specificity (positives are usually positives)

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23
Q

Explain PCR toxic gene
What does it test for?
What are limitations?
Highly sensitive/specificity

A

What does it test for?
- looks for C. diff toxic gene

What are limitations?
- does not indicate if the strain is active or not
- just says that its able to produce the toxin

Highly sensitive and specificity

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24
Q

Interpret the result:
Antigen negative

A
  • No c. diff present
  • Patient does not have CDI
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25
Q

Interpret the result:
Antigen positive, toxin positive

A
  • C. diff + toxin present
  • Patient HAS CDI
26
Q

Interpret the result:
Antigen positive, toxin negative

A
  • C. diff present
  • Either toxin not present or toxin is present in low amount (false negative)

**must perform a PCR

27
Q

Interpret the result:
PCR negative

A
  • C diff present but NOT toxigenic
  • Patient does not have C. diff
28
Q

Interpret the result:
PCR positive

A
  • C diff present and toxigenic (don’t know if making toxin or not)
  • could either have CDI or not +/-
29
Q

Does a positive culture of C. diff suggest diagnosis?

A

No

30
Q

If stool test is positive and symptoms resolve before what do you do?

A

No need to treat

31
Q

If patient has severe symptoms but still waiting for stool test results what should you do?

A

Start ABX

32
Q

What are 4 goals for CDI

A
  1. Prevent spread to others
  2. Cure infection
  3. Prevent complications
  4. Prevent recurrence
33
Q

How do we usually manage CDI (5)

A
  1. infection control
  2. Address risk factors (stop PPI if possible)
  3. Supportive measures (rehydration)
  4. Simplify bowel assessments (stop meds such as laxatives, opioids, antiperistaltics)
  5. Start ABX therapy
34
Q

What type of therapy is treating C. dif

A

Targeted

35
Q

Is there resistance with C. diff

A

No

36
Q

What are risk factors for C. diff (7)

A
  • 65+
  • immunocompromised
  • Fever 38+
  • increase in Scr greater than 50% OR significantly reduced urine output
  • WBC greater than 15 x 10^9
  • Albumin less than 30 g/dL
  • Abdominal examination consistent with peritonitis
37
Q

What do signs of shock look like? (4)

A
  • systolic BP less than 90 or 40 above normal
  • urine output less than 0.5L/kg/h
  • Decreased level of concousness
  • serum lactate greater than 2 mmol/L
38
Q

Define mild to moderate CDI

A

Patient has less than 2 risk factors + no signs of shock

39
Q

Define severe CDI

A

Patient has 2+ risk factors + no signs of shock

40
Q

Define complicated/fulminant disease

A

Patient is in shock OR has ileus/toxic megacolon

41
Q

What is the preferred treatment for mild-moderate CDI and alternative options. Give dosing

A
  1. Vancomycin 125mg PO QID x 10-14 days
  • Fidaxomicin 200mg PO BID x 10 days
  • Metronidazole 500mg PO TID x 10-14 days
42
Q

What is the preferred treatment for severe uncomplicated CDI and alternative options. Give dosing

A
  1. Vancomycin 125 mg PO QID x 10-14 days
  • Fidaxomicin 200mg PO BID x 10 days
43
Q

What is the preferred treatment for complicated CDI and alternative options. Give dosing.
What if ileus is also present?

A

Vancomycin 125-500mg PO QID + metronidazole 500mg IV q8h

  • fidaxomicin 200mg PO BID + metronidazole 500mg IV q8h

What if ileus is also present?
- consider adding Rectal vancomycin 500mg q6h

44
Q

What is the efficacy and safety and adherence of vancomycin?

A

Efficacy
- better efficacy than metronidazole
- lowers risk of recurrence

Safety
- well tolerated
- bad oral bioavialability so drug stays in the gut
- can increase colonization with vanco resistant enterococcus

Adherence:
- QID
- 200$ need LU outside of hospital

45
Q

What is the treatment for mild CDI if they are not in the hospital and do not wanna pay.

A

metronidazole TID for 10-14 days
- with mild diarrhea

To get vancomycin covered:
- Has to fail metronidazole

45
Q

What is the efficacy and safety and adherence of fidaxomicin? Why do we not use?

A

Efficacy
- same as vancomycin
- BEST for less risk recurrence

Safety
- well tolerated
- no oral biovailability so drug stays in gut
- minimal impact on normal flora

Adherence
- BID
- very expensive $1600 need EAP

45
Q

When can you give Fidaxomicin according to the criteria for EAP (4)

A
  • a third episode of C. Diff within 6 months
  • has experienced treatment failure with oral vancomycin (no improvement within 7 days)
  • has an IgE reaction to oral vanco
  • has experienced a severe adverse reaction or intolerance to vancomycin that resulted in D/C therapy
46
Q

What is the re-treatment criteria of Fidaxomicin for CDI?

A

re-lapse within 30 days
- 30 days+ go with vanco

47
Q

What is the efficacy and safety and adherence of metronidzole?

A

Efficacy
- not as good as vanco
- during diarrhea it is secreted in colon (when diarrhea is resolved, it decreases secretion to the colon–> ineffective)

Safety
- good oral bioavailability does not stay in gut
- may increase risk for colonization with vancomycin-resistant enterococcus

Adherence
- TID
- not expensive

48
Q

When do you give vancomycin 125mg vs 500mg in complicated CDI. How long does it take for ileus to resolve usually

A

125mg
- in complicated CDI

500mg
- in complicated CDI + ileus

ileus: resolves in 5-7 days

49
Q

How long do people have complete resolution by?

A

50% have complete resolution by day 9

50
Q

What do you do if there is no improvement 5 days?

A
  • consider alternative diagnosis for diarrhea
  • ensure adequate concentrations at site of infection
51
Q

Why should we not repeat stool testing at the end of therapy?

A

toxins can be detected up to 30 days following cure

52
Q

Define Recurrent CDI. What is timeline? why does it occur?

A

Presence of symptoms AND toxins within 8 weeks of effective therapy

Normal flora has not returned to normal yet
- relapse from persistent spores in gut or reinfection from environment

53
Q

What are risk factors of recurrent CDI

A
  • age 65+
  • initial infection with NAP1 strains
  • impaired immune response
  • using METRONIDAZOLE for treatment of initial episode
  • using PPI during CDI therapy
  • use of other ABX during CDI therapy

***Risk increases with each recurrence

54
Q

When diagnosing for rCDI, what can differentiate between IBS and rCDI following resolution of CDI

A

More likely when diarrhea is alternating with constipation

55
Q

What is the difference in treatment for rCDI for first recurrence, mild to moderate?

A

Vancomycin 125mg PO QID x 14 DAYS

56
Q

What is the difference in treatment for rCDI for first recurrence, severe uncomplicated?

A

Vancomycin 125mg PO QID x 14 days

57
Q

How to treat second or subsequent Recurrence of CDI

A

Vancomycin taper, then consider fecal microbiota transplant (FMT)

58
Q

What is the benefit of vancomycin tapering (2)

A
  • Drug-free period allow spores to germinate then be susceptible to ABX
  • lower drug exposure to allow restoration of normal flora
59
Q

What can we do to prevent CDI?

A
  • Antimicrobial stewardship
  • Avoid unnecessary use of PPI
  • Infection prevention and control
  • Vancomycin prophylaxis