Flashcards in Lecture 21 - Respiratory Tract Infections 2 Deck (31):
What are some of the things have we learnt from Pneumococcus?
• Gram stain
• bacterial serotypes
• polysaccharide antigens (capsule)
• role of DNA
• protein virulence determinants
What are the antibodies to pneumococcus directed against?
What is opsonisation?
Covering of the bacteria with immunoglobulins and complement
What was the first protein virulence determinant studied?
Describe the first demonstration of transformation
Live unencapsulated pneumococci (serotype 2) given to mouse --> no disease
Killed encapsulated pneumococci --> no disease
Live unencapsulated and killed encapsulated --> death
The live unencapsulated bacteria changed their phenotype by picking up DNA from the encapsulated bacteria
When was transformation first demonstrated?
In 1923 by Griffith
Describe the features of Optochin
What is it used for?
1911: effective in mice
1912: resistance emerges
1912: toxin in humans
Only used for detecting of pneumococci
Not used as antibiotic in humans
What are sulphonamides?
Describe the evolution
1938: efficacy shown
1943: emergence of resistance
What are the antimicrobials used against pneumococci?
Who discovered penicillin?
What does multiple resistance mean?
The strain is resistant to three or more antimicrobial agents
What has happened with resistance to antimicrobial agents over the years?
More and more quickly, the bacteria are becoming resistant to the agents
What is the mechanism of action of penicillin G?
Binds to this enzyme more strongly than the natural substrate
Prevents cross linking of peptidoglycan bricks
The cell wall can't form
What are beta-lactams?
Antimicrobials such as penicillin g
What are penicillin binding proteins?
How does resistance to penicillin evolve?
Modified penicillin binding protein active site
Can still link the protein chains of the peptidoglycan
What does the clinical significance of resistance depend on?
• whether the bacterium is a pathogen
(Eg. If a commensal is resistant, it doesn't matter)
• extent of resistance
• effect of resistance on outcome of treatment
What is the consolidation in the lung in lobar pneumonia
• Influx of fluid
Which diseases does S. pneumoniae cause?
• Middle ear infection (otitis media)
What is the relationship between amount of antimicrobials prescribed and resistance to the agent?
More prescription: more resistance
Which regions have a greater and lesser extent of resistance?
How do we detect resistance in a lab?
1. Dilution test
2. Diffusion tests
What things affect outcome of treatment?
• Type of infection (meningitis, septicaemia)
• Serotype of bacterium (more or less resistant)
What does this stand for?
Minimum inhibitory concentration
1. Dilute the antibiotic out into tubes
2. Add standard number of bacteria to each tube
3. Incubate overnight
4. Score for growth
5. Look for the lowest concentration that provides resistance
Describe the different types of distribution of susceptibility seen in bacteria
All or nothing:
Accumulation of mutations in binding site of penicillin binding proteins
Describe the disk diffusion test
1. Take standard suspension of bacteria from patient, lawn culture
2. Add disks with standardised concentration of antimicrobial agents
4. Radial diffusion of antibmicrobial from the disk, decreasing concentration
5. Measure the size of the zone of no growth
How big is the zone diameter?
And vice versa?
Very big diameter: low MIC, highly susceptible
Very small diameter: high MIC, highly resistant
What happened with linezolid?
• Resistance in less than a year
How do we deal with resistance?
• Other drugs
• New drugs
• Antibodies / Immunoglobulins that are able to opsonise
• Peptide that jazzes up the immune response against pneumococcus
• Altered trafficking of macrophages