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2021-22 Clinical microbiology > Gastrointestinal infection; Clostridioides difficile. > Flashcards

Gastrointestinal infection; Clostridioides difficile. Flashcards

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1
Q

What is a Food-associated (borne) infection?
Give an example

A
  • ‘Food’ acts as a vehicle for transmission
  • Food-handlers contaminate ‘food’
  • Consume the pathogen
    Eg. Salmonella sp. Campylobacter sp. E. coli O157, Norovirus

Risk caused by eating contaminated or undercooked food.

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2
Q

What is food poisoning?

A

• Organism grows in the food and produces a toxin ; toxin consumed

Eg. Staphylococcus aureus

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3
Q

What is Antibiotic-associated diarrhoea (AAD)?

A
  • Broad spectrum antibiotics disrupt normal gut flora
  • Over-growth of pathogenic microorganisms

Eg. Clostridium difficile (Clostridioides difficile)

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4
Q

When was clostridium difficile discovered?

A

Discovered in 1935

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5
Q

Give some background about clostridium difficile

A

Called Bacillus difficilis when it was first discovered as it was difficult to grow: normal component of faecal flora of 70% newborn babies and 2-3% healthy adults

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6
Q

What are the physiological characteristics of clostridium difficile?

A
  • Gram positive rod
  • Strictly anaerobic
  • Spore forming microorganism _(_ubiquitous)
  • Toxin producing (toxin A and toxin B)

More than 100 different genetic types (Ribotypes)

-Ribotypes 001, 106, 027 are common in UK

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7
Q

1978- Making its mark in the NHS:

A

Association with antibiotic associated diarrhoea (AAD) and pseudomembranous colitis (PMC) (>65 year-olds)

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8
Q

Describe clostridium difficile in the 21st Century

A

•C. difficile is one of the leading Healthcare Associated Infection (HAI) in the UK; AAD, PMC, death.

Spores are the VECTOR for transmission of CDAD

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9
Q

Graph showing the number of Healthcare Associated C. difficile reports, England / Wales (1990 - 2005)

A

Exponential increase in

C. difficile reports! What are we doing wrong in hospitals?

Largely due to the overuse of antibiotics (clinical practice, veterinary care etc)

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10
Q

Number of C. difficile reports, England and Wales (2003 - 2012)

A significant decrease in the number of reported cases. How have we improved?

A
  • Clean your hands campaign introduced by the government. 7 step handwashing technique to increase public awareness (2004)
  • Matrons brought back in for wards to ensure proper deep cleaning and disinfectants (2008)
  • Use of narrow spectrum antibiotics
  • Kill spores by vaporising hydrogen peroxide or using UV light
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11
Q

Show the number of death certificates mentioning Clostridium difficile, by whether it was the underlying cause of death (2006 - 2010)

A

Still need to eliminate the spores!

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12
Q

How many deaths were due to C. difficile in 2016?

A

1700 deaths due to / associated with C. difficile

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13
Q

Describe C. difficile Pathogenesis: Spore Formation

A
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14
Q

What are spores?

A

•Spores: persistent; transmissible; resistant to antimicrobials (70% IPA, antimicrobial

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15
Q

What are the risk factors for acquisition of C. difficile infection?

A
  • Hospitalisation; length of stay
  • Age (>65y) more likely to have other co-morbifitird
  • Broad spectrum antibiotic use-Hygiene / dirty environment-Close proximity of patients
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16
Q

What are some other risk factors?

A
  • Naso-gastric tubes
  • Contaminated equipment eg.

BP monitoring cuffs

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17
Q

C. difficile: Give a summary of the Infection Pathway

A
  • Susceptible patient ingests spores; resist stomach acid
  • SI: Favourable conditions for C. difficile SPORE GERMINATION; pH (6-6.8); bile salts (sodium taurocholate); 5 most effective co-germinant amino acids (glycine, histidine, aspartic acid, arginine, valine)

Calcium important as well

  • Vegetative cells: flagellated; metabolically active –produce potent toxins - symptoms
  • Vegetative cells produce spores in the colon;

excreted in diarrhoea

•Spores survive in clinical setting…….

RESISTANT TO ANTMICROBIALS

The infection cycle continues, they travel to the colon and produce spores themselves

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18
Q

Describe the germination of C. difficile spores (in the SI)

A

Irreversible process where a highly resistant, dormant spore is transformed into a metabolically active cell

19
Q

Germination occurs in stages:

A
  1. Germination initiation: (germinants: sugars, aa, nutrients, bile salts)
  2. Loss of heat resistance and ions (K+, H+, Na+) and Ca-DPA complex
  3. Partial rehydration of core
  4. Hydrolysis of cortex and degradation of SASPs
  5. Rehydration of core and restoration of metabolic activity
  6. Sensitive to antimicrobials
20
Q

Describe Germinate to Exterminate: The Aston Approach: Worthington et al

A

Spore=resistant to antimicrobials⇢ Patented germination solution⇢ Germinating cell =sensitive to antimicrobials

Combining the use of germinants in solution with traditional biocides

21
Q

C. difficile virulence factors: Adherence and multiplication

A
  • S-layer proteins (adhesins)
  • Flagella (motility and attachment)
22
Q

C. difficile virulence factors: Toxin production

A
  • Genes located on PaLoc
  • Toxin A: (enterotoxin)
  • Toxin B: (cytotoxin)

tcdD (positive regulatory)

tcdC (negative regulator)

23
Q

C. difficile virulence factors- What are the functions of Toxins?

A
  • Modification of Rho proteins
  • Stimulate cytokine production
24
Q

C. difficile: Draw the mechanism of Action of Toxins A and B

A
  1. Ingestion of C difficile
  2. Toxins bind to cells of GI tract and cross the membrane
  3. Inhibit function of Rho-GTP
  4. Immune stimulation to produce TNF-alpha and IL-8
25
Q

Clinical Spectrum of Clostridium difficile Infection

A
  • Asymptomatic (25% strains non-toxin producers)
  • Explosive diarrhoea (release of organisms vegetative organisms and spores)
  • Pseudomembranous colitis (PMC)•
  • Fulminant colitis (3%) very sever and fast onset
  • Death
26
Q

Clostridium difficile ribotype 027: ‘The Superbug’

A

•2003: Canadian outbreak

  • “7000 sufferers and 600 deaths in Quebec”-•C. difficile ribotype 027
  • Produces higher than normal levels of toxins A and B due to base pair deletion in toxin regulating gene
  • Resistant to ciprofloxacin / moxifloxacin
27
Q

2004: 027 hits UK:

A
  • (2004) Stoke Mandeville; 12 deaths, 300 infections
  • (2005) Royal Devon and Exeter; 13 deaths
  • (2006) Maidstone and Tunbridge Wells;

90 deaths, 1170 infections

28
Q

PaLoc (pathogenicity locus)

A

tcdC: single bp deletion at position 117

18-bp deletion at position 330-347

29
Q

What caused the outbreaks of Clostridium difficile at Maidstone and Tunbridge Wells NHS Trust?

A
  • Close Patient contact
  • Filthy conditions

(a) Shower cubicles
(b) Eating / drinking area
(c) Faecal stained patient commodes

30
Q

Laboratory Diagnosis of C. difficile Associated Diarrhoea

A
  • Clinical sample: faeces (diarrhoea)
  • Category 2 pathogen (ACDP)
  • Non culture techniques;
  • toxin detection (cell lines / EIA)
  • GDH detection (EIA)
  • Culture: selective agar (CCFA)
  • Typing: ribotyping (outbreaks)
31
Q

Non-culture techniques: toxin detection- What is the traditional method?

A

(Cell lines: (eg HeLa, Hep2)

  • Typical cytopathic effect; neutralised with C. sordelli antitoxin
  • Sensitivity: 94-100% (10pg of toxin) / Specificity: 99%
  • Disadvantage: 1-3 days / facilities / contamination
32
Q

Non-culture techniques: toxin detection- What is the modern method?

A

EIA (lateral flow)

  • Sensitivity 71-94% (detects 100-1000pg of toxin)
  • Rapid
  • Detects toxins (and GDH -glutamate dehydrogenase)
33
Q

Describe the laboratory Diagnosis of clostridium difficile (culture)

A

•Selective CCFA (cefoxitin, cycloserine, fructose) 48h/370C/ grown anaerobically

34
Q

Identification of C. difficile colonies on CCFA

A

(a) Ground-glass appearance
(b) Odour of colonies (horse-manure: p-cresol, isocaproic acid, and/or isovaleric acid unique)
(c) API® RAPID ID 32A

35
Q

Typing of Clostridium difficile:

Why Ribotyping?

A

•Genomic DNA encoding for 16S and 23S rRNA is a highly conserved region i.e. genetic information coding for rRNA will vary much less within bacteria of the same strain than it will between different strains: highly discriminatory

Important epidemiological tool (eg. Surveillance / Outbreaks)

36
Q

Describe the basic principle of ribotyping

A
  • C. difficile genomic DNA is digested with appropriate restriction endonucleases and separated by gel electrophoresis
  • Specific universal oligonucleotide probes target conserved regions (ie 16S and 23S rRNA coding region)
  • Visualized (eg. ethidium bromide or equivalent)
  • Band pattern compared to a database of established C.difficile ribotypes
37
Q

cribWhat is a Food-associated (borne) infection?
Give an example

A
  • ‘Food’ acts as a vehicle for transmission
  • Food-handlers contaminate ‘food’
  • Consume the pathogen
    Eg. Salmonella sp. Campylobacter sp. E. coli O157, Norovirus
38
Q

Describe antibiotic treatment strategies for C. difficile infection

A
  1. Discontinuation of precipitating antibiotic
  2. Replacement fluid and electrolytes
  3. Antibiotics for treating C. difficile

Oral vancomycin (250mg QDS; 10-14 days)

Oral metronidazole (250mg QDS; 10-14days)

39
Q

Describe biotherapy treatment strategies for C. difficile infection

A

Aim: to restore the gut microbiome

  • Probiotics (Saccharomyces boulardii)•
  • Faecal transplantation
40
Q

Prevention of C. difficile infection: Antibiotic use

A

Strict control of antibiotic use

•Narrow spectrum antibiotics

41
Q

Prevention of C. difficile infection: enteric precautions

A

Prompt implementation of enteric precautions

  • Isolation of patient eg. cohort wards
  • Effective hand hygiene
  • Disposable equipment eg. single use rectal thermometers
42
Q

Prevention of C. difficile infection: Elimination of spores from the environment

A
  • Spores resistant to common disinfectants eg. 70% alcohol
  • Hypochlorite / superoxides
  • Soap / detergent and scrubbing
43
Q

GI Infections –key points

A

•GI infection is a major cause of morbidity and mortality worldwide

  • C. difficile is the leading HAI in the UK
  • Produces highly resistant, dormant, spores –vehicle of transmission
  • Many risk factors; broad spectrum antibiotics
  • Spores germinate in SI and produce 2 toxins (A/B) resulting in: explosive diarrhoea – death)••Hyper-virulent ribotype O27 strain now exists; excessive toxin production
  • Treatable; biotherapy may aid patient treatment / management••Preventable: control antibiotic use / hygiene / eliminate environmental spores

2021-22 Clinical microbiology (10 decks)

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