clostridioides difficile

what type of bacterium is clostridioides difficile?

gram-positive bacillus (rod-shaped)

how does the presence of c.difficile change in different levels of healthcare interaction?

present in:

healthy adults - <2%

long-term care facility pts - 7%

inpatients - 3-26%

what are the two important strains of c.difficile?

- toxigenic (70-90%)

- nontoxigenic (10-30%)

what is the main feature of toxigenic c.difficile?

produces and releases exotoxins A + B - pathogenic

what is the main feature of nontoxigenic c.difficile?

cannot produce exotoxins - colonises without causing disease

how is c.difficile transmitted?

faeco-oral

what can both nontoxigenic and toxigenic c.difficile do?

release spores

what are the spores resistant to?

- acid

- heat

- antibiotics

when do spores convert into a fully functioning state?

after ingestion, in the host intestines

what is the key trigger leading to pathogenesis of c.difficile?

antibiotics

what happens when antibiotics are introduced to the gut?

- disrupts normal colonic microbiota

- allows toxigenic strains of CD to multiply and release toxins

what do the toxin A and B do to the colon? (2)

- promote colonic inflammation

- cause intestinal fluid secretion

- mucosal injury

- neutrophil chemotaxis and activation

what is the difference between the toxigenicity of toxins A and B?

B is 10x more virulent than A

what are the risk factors for CD? (8)

- antibiotic use

- >65 years of age

- hospitalisation

- severe co-morbidities

- gastric acid suppression

- enteral feeding

- GI surgery

- chemotherapy

which antibiotics cause a greater risk of CDI? (4)

- fluoroquinolones

- clindamycin

- broad-spectrum penicillin

- cephalosporins

what other features to do with antibiotics increase the risk of CDI? (2)

- using multiple antibiotics

- prolonged duration of antibiotics

what is the main symptom associated with CDI?

diarrhoea

what is diarrhoea defined as?

passage of 3 or more loose bowel motions in 24 hours

what are the other potential symptoms of CDI?

- abdominal pain

- anorexia

- nausea

- fever

how is CDI graded?

severity of colitis

what are the 4 stages of CDI?

1) mild

2) moderate

3) severe

4) fulminant

what is mild CDI? (2)

- diarrhoea without systemic features

- WCC normal

what is moderate CDI? (2)

- 3-5 bowel motions a day

- raised WCC but < 15

what is severe CDI?

- WCC > 15

- rising creatinine

- fevers > 38.5

- evidence of severe colitis

what is fulminant CDI?

- hypotension and shock

- toxic megacolon

- ileus

what is ileus?

loss of peristalsis

what is toxic megacolon?

extreme dilation and immobility of the colon

how is the diagnosis confirmed alongside acute diarrhoea?

stool testing

what are the main two ways of carrying out stool testing?

- nucleic acid amplification testing (NAAT)

- enzyme immunoassay (EIA)

what does nucleic acid amplification (PCR-based testing) do?

detects one or more genes specific to the toxigenic strain

what is the downfall of the nucleic acid amplification test?

inability to distinguish between asymptomatic carriage of a toxigenic strain and active CDI

what are the two types of enzyme immunoassay (EIA)?

- c.diff enzyme glutamate dehydrogenase

- c.diff toxin A+B

what does EIA enzyme glutamate dehydrogenase do?

detects the enzyme produced by all the strains

what does EIA c.diff toxin A+B do?

detects the toxin produced by the toxigenic strains

what is the downfall of EIA c.diff toxin A+B?

high false-negative rate

what blood tests should be done for CDI?

- full blood count

- U&E

- LFTs

- bone profile

- lipase

- blood cultures

- venous blood gas (for lactate)

what would be found from the venous blood gas?

- metabolic acidosis

- hypokalaemia

what imaging could be done for CDI? (30

- radiograph - for muscosal wall thickening

- CT abdomen and pelvis - for severe disease

- endoscopy

what could be observed upon endoscopy?

classical pseudomembranous colitis

what is classical pseudomembranous colitis?

yellow plaques over muscosa duw to toxin-induced ulcer formation

what are the main principles of management for CDI?

antimicrobial agents and infection control measures

what should all pts receive? (8)

- correct fluid losses

- VTE prophylaxis

- nutritional support

- stop laxatives

- stop antibiotics unless necessary

- review need for PPI

- stop anti-motility drugs

- consider other causes of diarrhoea

what are two examples of anti-motility drugs?

- codeine

- loperamide

what is codeine?

analgesic

what is loperamide?

anti-diarrheal

what is the medication used in mild-moderate CDI? (2)

- vancomycin

what is the medication used in severe CDI?

- vancomycin

- fidaxomicin

(add metranidazole if no improvement)

what medication is used in fulminant cdi?

- vancomycin (increased dose)

- metronidazole

how does metronidazole work?

binds to bacterial DNA to inhibit DNA synthesis

what type of antibiotic is vancomycin?

glycopeptide

how does vancomycin work?

inhibits cell wall synthesis by binding to protein ending in D-ala D-ala

what type of antibiotic is fidaxomicin?

macrolide

how does fidaxomicin work?

inhibits RNA polymerase

what are the key infection control measures?

- early detection

- isolation

- contact precautions

why is soap and water preferred over alcohol-based gels?

spores are resistant to alcohol

what is antibiotic stewardship?

process of providing recommendations for the safe and effective use of antibiotics - to help prevent resistance

what is faecal transplant?

transferring a solution of faecal matter from a highly selected donor to the intestinal tract of the recipient

what is the aim of a faecal transplant?

change the composition of the recipients intestinal microbiota

when might faecal transplant be used?

in refractory or recurrent CDI