Infectious disease & CDI

Question 1

Definition of Acute Infectious Disease

Answer 1

Acute: Increased freq of defecation lasting < 14 days
Diarrhoea: >= 3 loose/liquid stools OR
More frequent than normal
- Caused by 1/more micro-organisms

Question 2

LO1: Microbiology of Acute Infectious Disease

Answer 2

1) Bacterial
- C.difficle, Vibrio cholera, E.coli, Shigella spp,
Salmonella typhi, Campylobacter jejuni

2) Protozoal
- Giardia intestinalis, Entamoeba histolytica, Cryptosporidium parvum

3) Viral (Most common)
- Noravirus, rotavirus, adenovirus

Question 3

Methods to diagnose Acute Infectious Disease

Answer 3

1) Fecal occult blood - Non-specific, look for blood
in stools
2) Ova & parasite - By microscopy
3) Stool cultures - Takes few days, so not commonly done
4) PCR - More rapid, can look for multiple targets @ once
Quite ex

Question 4

Who are diagnostic tests for Acute Infectious Diseases reserved for?

Answer 4

• Severe illness
• Persistent fever
• Bloody stools
• Immunosuppression
• Unresponsive to treatment
• Usually not indicated, most cases are self-limiting

Question 5

How to prevent Acute Infectious Diseases?

Answer 5

1) Good hand & food hygiene practices
2) Vaccinations
- For travellers to endemic areas: Cholera, typhoid
- 6months-5y/o: Rotavirus

Question 6

Treatment of Acute Infectious Diseases

Answer 6

Non-pharmacological:

• Early re-feeding as tolerated
• Easily digestible food (eg. cereal, bananas)

Pharmacologic

• Self-care: Oral rehydration therapy, anti-peristaltics, adsorbents, probiotics
• Antibiotics (for PR3124) [MOST cases self-limiting]

Question 7

Indications for antibiotics for Acute Infectious Diseases

Answer 7

1) Severe disease
- Fever with bloody diarrhoea/ mucoid stools/ severe abdominal pain

2) Sepsis
3) Immunocompromised

Question 8

Clinical benefits of antibiotics for Acute Infectious Diseases

Answer 8

1) Decrease duration of symptoms (1-2 days)

2) Decrease morbidity & mortality

Question 9

Antibiotic regimen for Acute Infectious Diseases

Answer 9

1) IV Ceftriaxone 2g Q24h
2) PO Ciprofloxacin 500mg BD (if can’t tolerate B-lactam)

Duration of therapy: 3-5 days

• May be extended in bacteremia/ extra intestinal infections/ immunocompromised
• Rarely need to think about stepping down to PO

Question 10

What is Clostridioides difficile?

Answer 10

• Gram (+), spore-forming anaerobic bacillus
• -> Produces toxins A & B
• Most common cause of nosocomial diarrhoea
• Increases duration of hospitalization & healthcare cost

Question 11

How is Clostridioides difficile transmitted?

Answer 11

• Fecal-oral route
• Contaminated environmental surfaces
• Hand carriage by healthcare workers

(Often within hospital envt, C.diff form spores hence infected persons can be asymptomatic)

Question 12

Pathogenesis of Clostridioides difficile

Answer 12

• Normal gut flora is altered by broad-spectrum antibiotics
• C. difficile contains endospores that can survive acidity of stomach & reach the large intestine
• C. difficile flourishes in colon, produces toxins A & B that cause mucosal damage
• -> Bleeding, symptoms of C. difficile like fever, crampy abdominal pain, diarrhoea

Question 13

Risk factors for C. difficle

Answer 13

1) Healthcare exposure
- Prior hospitalisation
- Duration of hospitalisation
- Long-term care facilities/ nursing homes

2) Pharmacotherapy
- Systemic antibiotics (no. of agents, duration)
- High risk Abx: Clindamycin, fluoroquinolones
2nd gen Cephalosporins
- Use of gastric acid suppressive therapy
(Easier for spores to get into colon)

3) Patient-related factors
- Multiple/severe comorbidities
- Immunosupression
- Advanced age > 65yo
- History of CDI (May have recurrence)

Question 14

Clinical presentations of C. difficile

Answer 14

1) Mild
- Loose stools, abdominal cramps

2) Moderate
- Fever, nausea, malaise
- Ab cramps & distension
- Leukocytosis
- Hypovolemia

3) Severe/fulminant (rare but serious)
- Eg. ileus, toxic megacolon, pseudomembrance colitis, perforation, death

Question 15

Process of diagnosis for C. difficle

Answer 15

1) Clinical suspicion (Don’t have to be hospitalised/ on antibiotics)
- Unexplained + new onset of diarrhoea (ie. >= 3 unformed stools in 24hrs) OR
- Radiologic evidence of ileus/ toxic megacolon

2) Confirmatory test/ finding
- (+) stool test result for C.difficle/ its toxins OR
- Histopathologic findings of pseudomembranous colitis

Question 16

Diagnostic tests for C. difficile

Answer 16

1) Nucleic acid amplification test (NAAT)
- i) Toxin enzyme immunoassay (EIA): Looks for toxin A/B
- ii) Glutamate dehydrogenase (GDH) EIA:
Looks for enzyme

2) PCR

(Both have fast turnaround)

• Cultures not routinely performed due to long turnaround time
• Do not test asymptomatic patients
  (Based on clinical suspicion)
• Do not repeat testing in < 7 days (waste time & money)
• Do not perform test of cure
  –> Only monitor resolution of symptoms, don’t need to ensure clear of C. diff

Question 17

Infection control of C. difficile

Answer 17

Healthcare setting:

• Practice hand hygiene
• Contact precautions recommended for 48hrs after diarrhoea resolves (gloves, gown, wash hands with soap & water)

At home:

• Wash hands with water & soap after bathroom
• Use separate bathroom if possible
• Clean toilets, linens, towels, clothing with bleach

Question 18

When to recommend empiric CDI treatment?

Answer 18

1) Fulminant CDI

2) Substantial delay (>48h) in diagnostics

Question 19

Antibiotic regimen for C. difficile (1st episode)

Answer 19

Non-Severe (WBC < 15, SCr < 133):
i) PO Vancomycin 125mg QDS or
ii) PO Fidaxomicin 200mg BD
(Alternative) PO Metronidazole 400mg TDS

Severe (WBC >= 15, SCr >= 133):

i) PO Vancomycin 125mg QDS or
ii) PO Fidaxomicin 200mg BD

Fulminant (Hypotension/ Ileus/ Megacolon):
i) IV Metronidazole 500mg Q8h +
PO Vancomycin 500mg QDS
(+/-) PR Vancomycin 500mg QDS

Duration: 10 days (May extend to 14 if symptoms not completely resolved)

Question 20

Why is Metronidazole still used locally?

Answer 20

• Cost & logistic consideration
  (PO Vanco is prepared by compounded IV form to oral syringes)
• Avoid repeated/prolonged courses

Question 21

Benefits & Drawbacks of Fidaxomicin

Answer 21

• Narrow spectrum
• Lower MIC vs Metronidazole/Vancomycin
• Significant PAE
• Less alteration of normal gut flora
• May improve cure in immunocompromised patients

HOWEVER…

• $$$
• Hence, limited to severe &/or recurrent cases non-responsive to max standard therapy

Question 22

Antibiotic regimen for C. difficile (Recurrence)

Answer 22

1st recurrence:
[Metronidazole initially]: PO Vanco 125mg QDS x 10days
[1st line initially]: PO Vanco taper/
PO Fidaxomicin 200mg BD x 10days

2nd/subsequent recurrence:
i) PO Fidaxomicin 200mg BD x 10days
ii) PO Vancomycin taper
iii) PO Vancomycin 125mg QDS x 10days, 
    followed by Rifaximin 300mg TDS x 20days
iv) Fecal microbiota transplant

Question 23

Monitoring of C. difficile therapy

Answer 23

• Clinical improvement: ~ 5-7days

Do not continue C. difficle for concurrent antibiotics:

• -> Assess for indication to continue systemic
• Stop systemic –> C. diff Abx –> Continue systemic
• SERIOUS (eg. DFI): No choice, use concurrently

Question 24

Probiotics (Role, guidelines)

Answer 24

Contain: Saccharomyces boulardii/ Lactobacillus spp

Proposed mechanism: Maintain/restore healthy gut flora

Guideline recommendations:

• Not recc for routine use to prevent/treat CDI
• No harm to try unless immunocompromised

Question 25

Role of Anti-mobility agents? | Eg. loperamide, atropine, diphenoxylate

Answer 25

To provide symptomatic relief for diarrhoea by inhibiting contraction of intestinal smooth muscle - Limited role in infectious diarrhoea