Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

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

Gastrointestinal infection; Clostridioides difficile. Flashcards

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is food poisoning?

A

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

Eg. Staphylococcus aureus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When was clostridium difficile discovered?

A

Discovered in 1935

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

1978- Making its mark in the NHS:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

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

A

1700 deaths due to / associated with C. difficile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe C. difficile Pathogenesis: Spore Formation

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are spores?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are some other risk factors?

A
  • Naso-gastric tubes
  • Contaminated equipment eg.

BP monitoring cuffs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions