antimicrobial therapies Flashcards

1
Q
  • Define antibiotic

- What are most antibiotics used today produced by?

A

Antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms.

Target many different bacterial processes and are SELECTIVELY TOXIC

Soil-dwelling fungi (eg penicillin) or bacteria (streptomyces)
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2
Q
  • Define antimicrobial
  • Define bactericidal
  • Define bacteriostatic
  • Define antiseptic
A

Chemical that selectively kills or inhibits microbes

Kills bacteria

Stops bacteria growing

Chemical that kills or inhibits microbes, that is used to prevent infection
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3
Q
  • What was the first example of sulphonamide antibiotic?

- What is prontosil used to treat?

A

Prontosil

Urinary tract infections

Respiratory tract infections

Bacteraemia

Prophylaxis for HIV + individuals
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4
Q
  • What are the reasons for why antibiotic resistance may lead to increased mortality, morbidity and cost?
A

Increased time to effective therapy

Requirement for additional approaches e.g - surgery

Use of expensive therapy (newer drugs)

Use of more toxic drugs e.g- vancomycin

Use of less effective 'second choice' antibiotics
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5
Q
  • Give 2 examples of aminoglycosides

- What processes do aminoglycosides target?

A

Gentamicin, Streptomycin

Protein synthesis

RNA proofreading

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6
Q
  • What ribosomal subunit do aminoglycosides target?
  • Are aminoglycosides bactericidal or bacteriostatic?
  • What has lead to an increasing use of aminoglycosides?
A

30S

Bactericidal

Resistance to other antibiotics

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7
Q
  • What is the mechanism of rifampicin?

- What colour does rifampicin make your secretion go?

A

Targets RpoB subunit of RNA polymerase (bactericidal)
Spontaneous resistance is frequent

Orange/red (affects patient compliance)

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8
Q
  • What is the mechanism of vancomycin and is it bactericidal or bacteriostatic?
  • What has lead to increasing use of vancomycin?
A

Targets Lipid II component of cell wall biosynthesis, as well as wall cross-linking via D-ala residues
Bactericidal

Resistance to other antibiotics e.g. against MRSA
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9
Q
  • What spectrum of activity does linezolid have?

- What is the mechanism of linezolid?

A

Gram-positive spectrum of activity

Inhibits the initiation of protein synthesis by binding to 50S rRNA subunit (bacteriostatic)

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10
Q
  • What limits the dose of daptomycin?
  • What is the mechanism of daptomycin?
  • What is the spectrum activity of daptomycin?
A

Toxicity

Bactericidal - targets bacterial cell membrane 

Gram-positive spectrum
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11
Q
  • Give 2 examples of beta-lactams

- What is the mechanism of beta-lactams?

A

Penicillin, Methicillin

Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall (bind to penicillin-binding proteins)

Bactericidal
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12
Q
  • Give 2 processes that are unique to bacterial cells
A

Production of peptidoglycan

Maintenance of LPS layer of gram negative bacteria
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13
Q
  • Give 2 examples of macrolides
  • What types of infections can macrolides be used against?
  • Describe the mechanism of macrolides
A

Erythromycin, Azithromycin

Gram-positive, Some gram-negative infections

Targets 50S ribosomal subunit preventing amino-acyl transfer

Thus truncation of polypeptides
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14
Q
  • What do quinolones target in gram negative bacteria?

- What do quinolones target in gram positive bacteria?

A

DNA gyrase

Topoisomerase IV
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15
Q
  • What is meant by resistance?

- Why might there be more of a resistance to penicillin in hospitals than the community?

A

If a bacterium can grow at or above the breakpoint concentration (minimal inhibitory concentration of antibiotic)

Routine use of penicillin in hospitals provides a selection pressure

For the acquisition and maintenance of resistance genes
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16
Q
  • What are the 4 distinct mechanisms by which antibiotic resistance can occur?
A

Altered target site

Inactivation of antibiotic

Altered mechanism

Decreased drug accumulation
17
Q
  • Give 2 examples in which a target site can be altered
A

MRSA encodes alternative PBP with low affinity for beta lactams

Acquisition of erm gene by streptococcus pneumoniae encodes an enzyme that methylates AB target site in 50S ribosomal subunit
18
Q
  • How does inactivation of antibiotics occur?

- What is one of the greatest threats to antibiotic use at the moment?

A

Enzymatic degradation or alteration
Rendering antibiotic ineffective

Bacteria that encode broad spectrum of beta lactamase enzymes
Such as ESBL and NDM-1 which can degrade a wide range of beta-lactam
19
Q
  • How does the altered metabolism pathway occur within antibiotic resistance?
  • How does decreased drug accumulation occur?
A

Increased production of enzyme substrate can out-compete antibiotic for target site
Or bacteria can switch to other metabolic pathways, reducing requirement for PABA (if sulphonamide is drug used)

Reduced penetration of AB into bacterial cell
Or increased efflux pumps to keep AB out of cell
Makes it so that drug does not reach concentration required to be effective
20
Q
  • What are the 3 sources of antibiotic resistant genes and how do they work?
A

Plasmids - extrachromosomal circular DNA, often carry multiple AB resistant genes so selection for one maintains resistance for all

Transposons - integrate into chromosomal DNA and allow transfer of genes from plasmid to chromosome and vice versa

Naked DNA - DNA from dead bacteria released to environment
21
Q
  • Describe the 3 ways that bacteria can spread their AB resistant genes
A

Transformation - uptake of extracellular DNA

Phages - viruses infect bacteria and take up some of their DNA and then go on to infect other bacteria, passing on the DNA

Conjugation- bacterial sex to share plasmids between them

22
Q
  • Give some of the non-genetic mechanisms of resistance/treatment failure
A

Biofilm - matrix encased communities of bacteria that are highly drug tolerant will minimise penetrative effect of antibiotics

Intracellular location - harder for antibiotics to get to bacteria

Slow growth -hard for bacteria to inhibit replication processes if they do not occur as much

Persisters - dormant bacteria that are not carrying out the processes that antibiotics inhibit

Spores - resistant to heat, antiseptics and also antibiotics, spore coat is impermeable to antibiotics, preventing access to the target organelles
23
Q
  • What are 3 solutions to reducing antibiotic resistance?

- In what sectors are antibiotics used more?

A

Phage antibiotic combination therapy
Modifications of existing antibiotics (prevent cleavage)
Combination of inhibitor and antibiotic

Critical care
Wards
24
Q
  • What are some of the risk factors for HAI?
A

High number of ill people

Crowded wards

Presence of pathogens

Broken skin - surgical wound/IV catheter

Indwelling devices - intubation

AB therapy - may suppress normal flora

Transmission by staff - contact with multiple patients
25
Q
  • How might AB therapy impair commensal flora?
A

AB therapy removes commensal organisms

Pathogen has no competition leading to overgrowth

Pathogen produces toxins and damages host-symptomatic infection

Spreads to other patients
26
Q
  • Give some of the methods we might use to address resistance
A

Prescribing strategies - tighter controls, temporary withdrawal of certain classes and restrictions of ABs for certain serious infections

Reduce use of broad spectrum antibiotics

Quicker identification of infections caused by resistant strains

Combination therapies

Clinicians should have knowledge of local strains and resistance patterns
27
Q
  • What 3 broad classes of conditions are caused by fungi?

- What do fungi use in their cell membrane instead of cholesterol?

A

Allergy - allergic reactions to fungal products
Mycotoxicoses - ingestion of fungi or their toxic products
Mycoses - superficial, subcutaneous or systemic colonisation, invasion and destruction of human tissue

Ergosterol
28
Q

What are the three targets for antifungal therapy

A

Cell membrane- made from ergosterol rather than cholesterol

DNA synthesis- some molecules only activated by fungi. arresting DNA synthesis

Cell wall- fungi have cell wall unlike mammalian cells