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Clostridioides difficile Infection

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Diagnosis requires demonstration of the Clostridioides difficile toxin. The presence of Clostridioides difficile itself is not sufficient

Initial Management Summary
ABC, IV fluids, assess severity, send stool, Stop opiates and loperamide Mild disease oral Metronidazole 400-500 mg tds for 10-14 days Moderate/Severe Vancomycin 125 mg PO/NG qds for 10-14 days Failure try Fidaxomicin 200mg PO 12 hourly for 10 days Surgical review if toxic megacolon/perforation suspected If NBM then IV Metronidazole 500mg tds

Isolation if an infective cause suspected. Gown up and wear gloves, which should be placed in the bin in the patient's room. Ensure hands washed with soap and water to remove any C. difficile spores.

About

Clostridioides difficile is an anaerobic spore forming bacterium
Now called Clostridioides difficile
It is found in intestines.
It can be found in healthy people, where it causes no symptoms

Characteristics

Large gram-positive anaerobic terminal spore-forming rods
Irregularly shaped colonies on blood agar

Source

Found in the soil or in the bowel or in the environment as spores
Cultured from stool of 3% of population
Found in 30% of hospital patients and 66% of babies
Pathogenicity when antibiotics kill off other gut bacteria
This allows C. difficile to grow to unusually high levels.
It also allows the toxin that some strains of C. difficile produce to reach levels where it attacks the intestines and causes mild to severe diarrhoea.
It can lead to more serious infections of the intestines with severe inflammation of the bowel (pseudomembranous colitis).

Risks

Antibiotics, particularly the elderly
Those whose immune systems are compromised.

Aetiology

Toxin A - an enterotoxin and cytotoxic acts on gut mucosa
Toxin B - a cytotoxin that cause the death of colonic luminal cells
Third substance that inhibits bowel motility
Together these cause ulceration and diarrhoea
Ribotype 027 is associated with a very virulent form of infection with higher toxin production and quinolone resistance

Antibiotics associated

The use of broad-spectrum antibiotics is associated with PMC especially
Ampicillin, Amoxicillin, 2nd/3rd generation Cephalosporin
Clindamycin and quinolones

Pathology

Colonic inflammation and mucosal damage
Inflammatory exudate forms pseudomembranes
Due to infection with Clostridioides difficile (CD)

Clinical

Diarrhoea may begin within 4-10 days of antibiotic treatment but may be delayed up to 6 weeks
Asymptomatic to mild diarrhoea to pseudomembranous colitis
Copious liquid stool with Fever, malaise
Abdominal pain and distension and toxic megacolon, perforation and death

Investigations

FBC, U&E, LFT, AXR may suggest dehydration/prerenal failure
CT Abdomen if needed
C. difficile toxins A and B.
Colonoscopy/Sigmoidoscopy may show yellow adherent plaques
Anaerobic culture on cycloserine, cefoxitin and fructose (CCFA) media
Stools - the presence of CD toxin A and B which may need repeated
Stool culture to exclude other infective causes
AXR/CXR exclude perforation, ileus, megacolon

Differentials

Diarrhoea due to NG and PEG feeds
Salmonella, Shigella, Campylobacter, E Coli 0157
Viral Gastroenteritis

Complications

Prerenal failure
Toxic megacolon and Colonic perforation

Severity Assessment

Mild
- WCC < 15 x 10⁹/l
- < 5 stools per day of type 5-7 on Bristol stool chart
Severe: any of these should suggest using oral vancomycin (or fidaxomicin) in preference to Metronidazole
- WCC > 15x 10⁹/l
- an acute rising serum creatinine (i.e. >50% increase above baseline)
- a temperature of > 38.5 C
- evidence of severe colitis (abdominal or radiological signs)
- The number of stools is a less reliable indicator of severity.
Life threatening CDI
- Hypotension
- Partial or complete ileus
- Toxic megacolon or CT evidence severe disease

Other markers of poor prognosis

CDI due to ribotype 027 strains is associated with increased severity
Elevated blood lactate >5 mmol/L even with colectomy

Management [Based on reference below]

Isolate patient, hand wash with soap and water on suspicion before toxin result. Supportive care should be given, including attention to hydration, electrolytes and nutrition. Fluid resuscitation and management.
Antiperistaltic agents should be avoided in acute infection. This is because of the theoretical risk of precipitating toxic megacolon by slowing the clearance of C. difficile toxin from the intestine. Avoid loperamide and similar. Stop any antibiotic if possible and stop PPI if possible.
Mild: Patients with mild disease may not require specific C. difficile antibiotic treatment. If treatment is required, oral Metronidazole 400 mg TDS for 10-14 days as it has been shown to be as effective as oral vancomycin in mild to moderate CDI
Moderate:For patients with moderate disease, a 10- to 14-day course of oral Metronidazole is the recommended treatment (dose: 400 mg TDS). This is because it is cheaper than oral vancomycin and there is concern that overuse of vancomycin may result in the selection of vancomycin-resistant enterococci
Severe: Oral Vancomycin 125 mg QDS for 10-14 days. This is superior to Metronidazole in severe cases of CDI. Fidaxomicin should be considered for patients with severe CDI who are considered at high risk for recurrence; these include elderly patients with multiple comorbidities who are receiving concomitant antibiotics
If severe cases not responding to oral Vancomycin then Fidaxomicin 200mg BD should be considered. Alternatively, high dosage oral Vancomycin (up to 500 mg QDS, if necessary administered via a nasogastric tube) plus IV Metronidazole 500 mg TDS is an option. Vancomycin levels not needed if it is given orally as no systemic absorption. The addition of oral Rifampicin (300 mg BD) or IV immunoglobulin (400 mg/kg) may also be considered.
Life-threatening disease (i.e. hypotension, partial or complete ileus or toxic megacolon, or CT evidence of severe disease) can be treated by vancomycin given via a nasogastric tube (which is then clamped for one hour) and/or by rectal installation
Surgical consult. Colectomy is required in some patients with megacolon (dilatation >10 cm), perforation or septic shock, and should be done before the blood lactate rises above 5 mmol/L. A recent systematic review concluded that total colectomy with end ileostomy is the preferred surgical procedure; other procedures are associated with high rates of re-operation and mortality. An alternative approach, diverting loop ileostomy and colonic lavage, has been reported to be associated with reduced morbidity and mortality.
Recurrent disease occurs in about 20% of patients treated initially with either Metronidazole or vancomycin. The same antibiotic that had been used initially can be used to treat the first recurrence. A variable proportion of recurrences are reinfections (20-50%) as opposed to relapses due to the same strain; relapses tend to occur in the first two weeks after treatment cessation.
Colectomy should be considered, especially if caecal dilatation is >10 cm. Colectomy is best performed before blood lactate rises > 5 mmol/L, when survival is extremely poor
Donor faecal transplant

References

Updated guidance on the management and treatment of Clostridioides difficile infection

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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