Clostridioides difficile

Matthew McGinn
The History of C. diff

❖ First described by Hall and

O’Toole in 1935
➢ Name “difficile” comes from
difficulty to plate
❖ First related to antibiotic-
associated diarrhea and
pseudomembranous colitis in
1978 by investigators
Bartlett and George

Figure 1. John G. Bartlett, John Hopkins Medicine (2021)

The Basic Biology of C. diff
❖ Obligate Anaerobe
❖ Obligate symbiote
(pathogen)
❖ Rod-Shaped
❖ Spore-forming Figure 2. C. diff under light microscope with spores, Thanissery (2018)

➢ Motile and anaerobic in

vegetative stage
■ Peritrichous flagella
➢ Sessile and metabolically
dormant in the endospore
phase
❖ Gram-positive
➢ S-layer with attachment
proteins
Figure 3. C. diff under electron microscope, Bremerd (2017)
Phylogeny of C. difficile
❖ First placed in the Bacillus
genus in 1935
❖ Shortly after moved to
Clostridium
➢ C. diff’s differences to C.
butyricum
➢ C. diff put into new family
Peptostreptococcaceae
❖ A name change was in
order
➢ Peptoclostridium difficile
floated
➢ Clostridioides difficile stuck
■ Retained C. diff title
Figure 4. Peptostreptococcaceae Phylogeny, Elliot et al. (2017)
C. difficile Infection
❖ C. difficile infection (CDI)
➢ leading cause of antibiotic-associated diarrhea and
pseudomembranous colitis (PMC)
❖ Dysbiosis
➢ Typically initiated by antibiotic treatments
❖ Spores ingested from food or surfaces
contaminated with infected fecal matter
❖ Spores germinate after sensing bile acids and
glycine
❖ Vegetative C. diff attach to the colonic epithelium
➢ Toxin A (TcdA) and Toxin B (TcdB) secreted
■ leaky gut

Figure 5. C. diff Transmission Path, Smits et al. (2016)

CDI Symptoms and Complications
❖ Watery Diarrhea
➢ Urgent need or incontinence
➢ Particularly foul-smelling
➢ Bloody (rare)
❖ Dehydration Figure 6. PMC Seen From Endoscopy, Azer & Sun (2023)

❖ Fever, Malaise, and Nausea

❖ Colitis
➢ abdominal pain and cramps
❖ Pseudomembranous colitis (PMC)
❖ Toxic megacolon
➢ Colonic perforation

Figure 7. Toxic Megacolon Illustration, Manji (2015)

 Diagnosis and Treatment
❖ PCR Assay
➢ Genes encoding toxins (tcdA and tcdB)
❖ Rapid Antigen Tests (Immunoassay) and
Toxin Test
➢ Finds antigen glutamate dehydrogenase (GDH)
➢ Tests for toxins A/B

❖ Antibiotic Treatment
➢ Vancomycin and fidaxomicin
■ Rarely resistant to antibiotics
➢ Dysbiosis worsens
➢ One in six patient experience recurrent infection

Figure 8. Rapid Testing Algorithm for CDI, Bagdasarian et al. (2019)

Fecal Microbiota Transplant (FMT)
❖ Provides recipient with fecal matter or
isolated microbiota from donor
➢ Provided through colonoscopy tube or taken orally
➢ Resets microbiome from dysbiosis
❖ Cure rate over 90% in most patient
populations
❖ Nevertheless, problems have arisen
➢ In 2019, two immunocompromised patients
received multi-drug resistant E. coli
➢ One did not survive
➢ More screening needed for donors
❖ FMT still incredibly promising
❖ Bezlotoxumab also promising
➢ Introduces antibodies neutralizing toxin B Figure 9. Fecal Transplant Overview, Cleveland Clinic
(2023)
References
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