Clostridium Difficile Diarrhoea Flashcards by Lin Weilin

What is defined as Acute Infectious diarrhoea?

Defined as passage of loose or watery stools ≥3 times in a 24‐hour period that lasts for <14 days
Noninflammatory (milder, usually viral) vs inflammatory (more severe, usually bacterial)

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How is acute infectious diarrhoea transmitted?

Fecal-oral route (likely)
– International travel
– Food or water borne
– Exposure infected animals or feces
– Recent antimicrobial use

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How is acute infectious diarrhoea usually managed?

Usually self-limiting disease (no abx)
Supportive care (ORT, anti-diarrhoeals, avoid spicy food etc...)

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How is diagnostic testing for acute infectious diarrhoea like?

– Recommended only in patients with diarrhea accompanied by fever, bloody or mucoid stools, severe abdominal cramping or tenderness, or signs of sepsis
– Test for Salmonella, Shigella, Campylobacter, Yersinia, Clostridium difficile, and Shiga toxin producing E. coli (STEC)

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When are stool cultures and PCR testing done for acute infectious diarrhoea?

Pts who have more invasive disease, unable to mount response, chemo, pts on immunosuppressive meds, persistent and non-responding diarrhoea

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When will abx therapy be recommended for acute infectious diarrhoea?

Patient has severe disease (fever with bloody diarrhea or mucoid stools ± severe abdominal cramping or tenderness)
or
Patient appears septic
or
Patient is an immunocompromised host (ICH)

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What is the empiric abx tx for acute infectious diarrhoea?

– Ceftriaxone 2g IV q24h or
– Ciprofloxacin 500mg PO BD (alternative)
– Duration: 3‐5 days
• Maybe extended in patients with bacteremia, extra intestinal infections and in ICH

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What are things to monitor for in acute infectious diarrhoea?

Assess for symptom resolution, clinical improvement

- If persistent, further workup might be required

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What are characteristics of Clostridioides difficile?

A gram‐positive, anaerobic, spore‐forming, toxin‐producing bacillus

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What is the pathogenesis of C. diff infections (CDI)?

Broad spectrum abx wipe out C. diff competition but not C. diff
More endospores survive GIT due to PPIs
- C. diff produces toxins and damages mucosal membrane

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Describe the range of clinical manifestations for CDI

– Diarrhea without colitis (≥3 episodes of unformed stools in 24h)
– Colitis (Fever, abdominal pain/cramps, nausea and anorexia)
– Severe colitis (Sepsis, significant leukocytosis, renal impairment)
– Fulminant colitis (severe + complicated colitis)
• Complications: toxic megacolon, colonic perforation, intestinal paralysis (ileus), pseudomembranous colitis

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What are the risk factors for CDI?

Abx exposure 
PPI/H2-antagonist use
Healthcare exposure
Poor host immunity (co-morbidities, elderly, immunocompromised etc..)
Previous CDI

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Which abx are the highest risk for CDI?

Clindamycin, 3rd/4th cephs, FQs (broad spectrum abx)

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When is the highest risk for CDI with regards to abx?

Highest risk during abx tx and up to 1 month post abx exposure
- Risk is exposure dependent

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How can CDI be diagnosed?

Both 1 and 2:
1. Unexplained and new ONSET diarrhoea* (≥3
unformed stools in 24h) OR Radiologic evidence of
ileus or toxic megacolon
2. Positive stool test result for toxigenic C. difficile AND its toxins OR Histopathologic findings of pseudomembranous colitis

*not due to drugs, must have liquid consistency, compare against pt baseline

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If a patient with an infection does not have diarrhoea, can we rule out CDI?

Ileus (complication of CDI) can prevent diarrhoea despite pt being infected with CDI

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What is something to note regarding CDI lab tests?

Repeat testing not recommended within 2 weeks of previous positive test (likely to remain positive)

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Can laboratory testing alone confirm presence of CDI?

No, as Laboratory testing alone cannot distinguish between asymptomatic colonization and clinical symptoms of infection

*Recall: C. diff is a normal gut commensal

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What are the stool tests available for CDI?

Glutamate dehydrogenase (GDH) EIA
Toxin A and B EIA
Nucleic acid amplification tests (NAAT) –> too sensitive = may have false positive i.e. asymptomatic or colonizer Cdiff/ (low bacterial load)

*at least 2 out these 3 tests must be positive for CDI diagnosis

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Which of the following statements regarding C. difficile infections is not true?
Select the most appropriate answer
A. Antibiotic use is the biggest risk factor for CDI
B. Asymptomatic patients should not be tested for C. difficile
C. Detection of C. difficile bacteria in stool is sufficient to make the diagnosis for CDI
D. Ileus can occur with severe illness
E. New onset diarrhea is one of the common presentations for CDI

Ans: C

Pt needs to have 2 things for CDI diagnosis

clinical symptoms (new onset diarrhoea w unformed stools or toxic megacolon, ileus)
labs (positive)

*Note for option E: pt might not have diarrhoea due to ileus

How is CDI transmitted?

– Likely via fecal‐to‐oral route
– In the healthcare setting, likely via exposure to contaminated environment or hands of healthcare personnel, transiently contaminated with C. difficile spores

What are some infection control measures for CDI?

– Isolation measures* (or cohorting) for infected patients
– Appropriate PPE when caring for infected patients
– Practice good hand hygiene before and after contact with patients
– Infection control strategies should be implemented in every suspected case, not only in confirmed cases

*Ends 48h after diarrhoea resolves

Is hand sanitizer enough to remove C. Diff from our hands?

No. C. diff spores are not killed off by handrub

What are some environmental management controls for CDI?

Sporicidal disinfectant to cleanse reusable equipment

How can we prevent and control CDI?

Infection control Environmental management Abx stewardship

What is the management plan for a patient presenting with s/sx of CDI?

Perform stool testing Stop precipitating antibiotics* (if possible) Stop drugs that can cause diarrhea** Initiate infection control measures * streamline abx tx and remove unnecessary abx * *Lactulose and sena

What is the management plan if a patient presenting with s/sx of CDI tests positive for CDI?

Initiate tx based on CDI episode (initial/recurrent) and severity

What is considered an initial episode of CDI?

No CDI episodes within the last 8weeks

For an initial episode, what are 2 key lab markers that indicate severe disease?

WBC ≥15 x 10^9/L OR | sCr ≥1.5mg/dL (133 mmol/dL)

How can we differentiate between severe CDI and fulminant CDI?

Presence of CDI complications (any one) - Ileus - Colonic perforation - Pseudomembraneous colitis - Toxic megacolon

What is considered a recurrent episode of CDI?

CDI within the previous 2-8weeks

HP 66y/F who was recently treated for cellulitis with a 7‐day course of clindamycin. She subsequently presented to the ED with new onset diarrhea and stool testing confirmed CDI. She had no prior diagnosis of CDI in the last 12 months. Her vital signs and pertinent labs were as follows: Temp: 39.20C, HR 89 bpm, RR 20 bpm, BP 114/58 mmHg, WBC 17.7 x 109/L Radiological imaging was consistent with toxic megacolon What is the severity of her CDI infection? A. Non‐severe CDI B. Severe CDI C. Complicated CDI D. Fulminant CDI E. Recurrence of CDI

Ans: D Risk factors: - elderly > 65 - Clindamycin Vitals: - >15 WBCs - severe - toxic megacolon - complicated

How can we treat a non-severe initial episode of CDI?

– Vancomycin (VAN) 125mg PO** q6h for 10 days – Fidaxomicin (FDX) 200mg PO q12h for 10 days^ • Alternative: Metronidazole 400mg PO q8h for 10 days* ^Fidaxomicin is currently not registered in Singapore * Guidelines recommend metronidazole 500mg PO q8h but in SG, it comes in 200mg tabs * *SG does not have PO tab --> uses IV vanco vials to reconstitute 125mg to drink, 10mL vial = 500mg (1 day)

How can we treat a severe initial episode of severe CDI?

– VAN 125mg PO q6h for 10 days – FDX 200mg PO q12h for 10 days^ – Metronidazole PO is NOT recommended ^Fidaxomicin is currently not registered in Singapore

A patient presents with Fever, abdominal pain/cramps, nausea and anorexia. Her labs show 12 x 10^9 WBCs and SCr of 2.5mg/dL. What is the appropriate abx tx for the pt?

VAN 125mg PO q6h for 10 days *assuming Vancomycin is tolerated

A patient presents with Fever, abdominal pain/cramps, nausea and anorexia. Her labs show 14 x 10^9 WBCs and SCr of 1.3mg/dL. What is the appropriate abx tx for the pt?

VAN 125mg PO q6h for 10 days *assuming Vancomycin is tolerated

How can we treat an initial episode of fulminant CDI?

– VAN 500mg q6h PO or via NG tube ± Metronidazole 500mg IV q8h – If ileus • Combination of VAN and metronidazole suggested • Consider adding PR VAN: VAN 500mg in 100ml NS PR q6h (rectal instillation via enema)

A patient presents with Fever, abdominal pain/cramps, nausea and anorexia. Her labs show 14 x 10^9 WBCs and SCr of 1.8mg/dL. Upon radiological imaging, toxic megacolon was found. Patient is unable to take tablets orally. What is the appropriate abx tx for the pt?

VAN* 500mg q6h NG tube + Metronidazole 500mg IV q8h + PR VAN 500mg in 100ml NS PR q6h (rectal instillation via enema) *assuming Vancomycin is tolerated

What are some advantages of FDX?

– Displays a narrow spectrum of activity – Bactericidal (vs vancomycin which is bacteriostatic) – Lower MICs against C. difficile – Prolonged post‐antibiotic effect, requiring less frequent dosing • Higher rates of symptomatic cure with FDX (vs VAN) • FDX is associated with lower CDI recurrence rates (vs VAN)

What are some disadvantages of FDX?

– Locally, not often stocked in hospital formularies – Limited data to support use in fulminant CDI – FDX is the most expensive of all three agents

How should a (first) recurrent CDI pt be treated if the initial episode was treated with Metronidazole?

VAN 125mg PO q6h for 10 days

How should a (first) recurrent CDI pt be treated if the initial episode was treated with VAN/FDX?

Prolonged tapered or pulsed VAN regimen VAN 125mg PO q6h x 10‐14 days --> q12h x 7 days --> q24h x 7 days --> every 2‐3 days for 2‐8 weeks

How should a (first) recurrent CDI pt be treated if the initial episode was treated with FDX?

FDX 200mg PO q12h for 10 days

If a pt has their 2nd or subsequent recurrence, what is the tx plan?

- Tapered or pulsed VAN regimen - VAN 125mg PO q6h x 10 days followed by Rifaximin 400mg PO q8h x 20 days - FDX 200mg PO q12h for 10 days - if abx tx failed for at least 2 recurrences --> fecal microbiota transplantation (FMT)

Mr JT is a 59y/M with background of allergy to vancomycin (angioedema). He was just discharged a few days ago after completing a 2 week course of antibiotics for line infection. Today he presents at the ID clinic with new onset diarrhea and stool testing was consistent with CDI. Background of hypertension and stroke. Had no previous episodes of CDI. His vital signs and pertinent labs were as follows: Temp: 36.50C, HR 80 bpm, RR 18 bpm, BP 134/68 mmHg, WBC 8.9 x 109/L What is the MOST appropriate treatment for his CDI infection? A. Fidaoxmicin 200mg PO BD for 10 days B. Metronidazole 500mg IV TDS for 10 days C. Metronidazole 400mg PO TDS for 10 days D. Vancomycin 125mg PO q6h for 10 days

C. Metronidazole 400mg PO TDS for 10 days ``` Risk factors: - recent hospitalization - recent abx use - co-morbs Diagnostics +ve ``` PO VAN not recommended as some systemic absorption can still take place (angioedema) - most hospitals dont keep FDX -> delay to bring in depending on approval process (need to tx pt asap)

Is red-man syndrome a sign of vancomycin allergy?

Red man syndrome is a hypersensitivity reaction to infusion -> can resolve when slowing down infusion rate - PO Van is still a choice

Are probiotics recommended for CDI?

+ Safe and well tolerated – Unclear if probiotics would remain active once exposed to CDI treatments (abx) – Bring about additional pill burden + costs

Are anti-motility agents recommended for CDI?

+ Symptomatic relief – Reduces bowel output, affecting ability to perform stool testing – May mask fluid loss – Associated with poor outcomes, especially if diarrhea is not treated appropriately

How can we monitor CDI therapy?

– Improvement in diarrhea frequency and consistency (Within a few days of initiating tx with near complete resolution anticipated within 10 days) – Resolution of leukocytosis – Not recommended to repeat stool testing to assess cure (A significant proportion would test positive despite improvement)