Lecture 21 - Respiratory Tract Infections 2 Flashcards Preview

MIIM20002 - Microbes, Infections, Responses > Lecture 21 - Respiratory Tract Infections 2 > Flashcards

Flashcards in Lecture 21 - Respiratory Tract Infections 2 Deck (31):
1

What are some of the things have we learnt from Pneumococcus?

• Gram stain
• opsonisation
• bacterial serotypes
• polysaccharide antigens (capsule)
• role of DNA
• protein virulence determinants
• vaccination

1

What are the antibodies to pneumococcus directed against?

The capsule

2

What is opsonisation?

Covering of the bacteria with immunoglobulins and complement

3

What was the first protein virulence determinant studied?

Pneumolysin

4

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

5

When was transformation first demonstrated?

In 1923 by Griffith

6

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

7

What are sulphonamides?
Describe the evolution

Antimicrobial

1938: efficacy shown
1943: emergence of resistance

8

What are the antimicrobials used against pneumococci?

Optochin
Sulphonamides
Penicillin G

9

Who discovered penicillin?

Alexander Fleming

10

What does multiple resistance mean?

The strain is resistant to three or more antimicrobial agents

11

What has happened with resistance to antimicrobial agents over the years?

More and more quickly, the bacteria are becoming resistant to the agents

12

What is the mechanism of action of penicillin G?

Targets Transpeptidase
Binds to this enzyme more strongly than the natural substrate
Prevents cross linking of peptidoglycan bricks
The cell wall can't form

13

What are beta-lactams?

Antimicrobials such as penicillin g

14

What are penicillin binding proteins?

Transpeptidases

15

How does resistance to penicillin evolve?

Modified penicillin binding protein active site

Can still link the protein chains of the peptidoglycan

17

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

18

What is the consolidation in the lung in lobar pneumonia

• Influx of fluid
• Neutrophils
• Bacteria

19

Which diseases does S. pneumoniae cause?

• Pneumonia
• Middle ear infection (otitis media)
• Meningitis

19

What is the relationship between amount of antimicrobials prescribed and resistance to the agent?

More prescription: more resistance

20

Which regions have a greater and lesser extent of resistance?

Most resistance:
• Africa
• Asia
• Spain

Less resistance:
• Australia
• USA
• Netherlands
• Sweden

21

How do we detect resistance in a lab?

1. Dilution test
2. Diffusion tests

22

What things affect outcome of treatment?

• Type of infection (meningitis, septicaemia)
• Age
• Serotype of bacterium (more or less resistant)
• Co-morbidity

23

Describe MIC
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

24

Describe the different types of distribution of susceptibility seen in bacteria

All or nothing:
Eg. Beta-lactamase

Spectrum:
Accumulation of mutations in binding site of penicillin binding proteins

25

Describe the disk diffusion test

Standardised

1. Take standard suspension of bacteria from patient, lawn culture
2. Add disks with standardised concentration of antimicrobial agents
3. Incubate
4. Radial diffusion of antibmicrobial from the disk, decreasing concentration
5. Measure the size of the zone of no growth

26

Low MIC.
How big is the zone diameter?

And vice versa?

Very big diameter: low MIC, highly susceptible

Very small diameter: high MIC, highly resistant

28

What happened with linezolid?

2000
• Resistance in less than a year

29

How do we deal with resistance?

• Other drugs
• New drugs
• Immunotherapy
• Immunisation

30

Describe immunotherapy

• Antibodies / Immunoglobulins that are able to opsonise
• Peptide that jazzes up the immune response against pneumococcus

Outcome:
• Altered trafficking of macrophages

31

What is a PBP?

Penicillin binding protein