Antimicrobial therapies Flashcards

1
Q

Define antibiotic

A

Antimicrobial agent produced by microorganisms that kills or inhibits other microorganisms

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2
Q

Define antimicrobial

A

Chemical that selectively kills or inhibits microbes

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3
Q

Define bactericidal and bacteriostatic

A

Kills bacteria

Stops bacteria growth - stops replication

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4
Q

Define antiseptic

A

Chemical that kills/inhibits microbes

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5
Q

Why don’t antibiotics harm human cells?

A

ABs have selective toxicity. They target different bacterial processes not found in mammals.

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6
Q

Which different bacterial processes do ABs target?

A
DNA replication
Cell wall synthesis
Plasma membrane damage
Protein synthesis
- Transcription
- Translation
Enzymatic activity/synthesis of metabolites
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7
Q

What is prontosil and what does it act on?

Why is it being used more now?

A

First sulphonamide - bacteriostatic and synthetic
Used for UTIs, RTIs, bacteraemia, prophylaxis for HIV patients
only works on gram positive bacteria
used more due to resistance to other ABs however has some host toxicity

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8
Q

Why are sulphonamides sometimes used with trimethoprim?

A

Sulphonamides target biosynthetic pathways such as folate synthesis
trimethoprim targets folate synthesis too
Used in conjunction they have synergic effects leading to more effective treatment

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9
Q

Give examples of beta-lactams and explain how they function

A

Penicillin or methicillin
Typically bactericidal - interfere with the synthesis of the peptidoglycan component of the bacterial cel wall
Binds to penicillin-binding proteins responsible for manufacturing the cell wall

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10
Q

Give examples of amioglycosides and explain how they function
Bactericidal or bacteriostatic?
Why are they dangerous to use?

A

Gentamicin
Streptomycin
Bactericidal - target protein synthesis by targeting 30s ribosomes, RNA proofreading and cause cell damage to membrane
Host toxicity - can cause hearing loss - used more due to AB resistance

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10
Q

Give examples of amioglycosides and explain how they function

A

Gentamicin
Streptomycin

Bactericidal

Targets protein synthesis, RNA proofreading and cause damage to cell membrane
Are toxic and can cause hearing loss

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11
Q

Give some examples of sulphonamides, what are they used in conjunction with?

A

Prontosil
Sufla-methoxazole

Used with Trimethoprim

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12
Q

What does Rifampicin do? Bactericidal or bacteriostatic?

What side effect does it have?

A

Bactericidal- targets RpoB unit of RNA polymerase which blocks transcription and has good activity on bacteria inside host cells ie neutrophils
spontaneous resistance is common, also causes red/Orange secretions so compliance is an issue

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13
Q

What does Vancomycin do? Bactericidal or bacteriostatic?

What side effect does it have?

A

Bactericidal - Targets lipid II component of cell wall biosynthesis as well as crosslinking via D-ala residues
Very toxic - must be given intravenously - used more for things like MRSA

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14
Q

What does Linezolid do? Bactericidal or bacteriostatic?

What type of bacteria does it act on?

A

Bacteriostatic - inhibits initiation of protein synthesis by binding to the 50s ribosomal RNA subunit
Only effective on gram positive bacteria

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15
Q

What does daptomycin do? Bactericidal or bacteriostatic?

What type of bacteria does it act on? Why is dosage limited?

A

Bactericidal
Targets bacterial cell membrane
active on gram positive bacteria - relatively toxic so limited dose

16
Q

Give some examples of macrolides. What does they do? Bactericidal or bacteriostatic?
What type of bacteria does it act on?

A

Erythromycin, azithromycine
Bacteriostatic
Target 50s ribosomal subunits preventing amino-acyl transfer and thus truncation of polypeptides
Mostly gram positive some gram negative

17
Q

What doe quinolones do? Bactericidal or bacteriostatic?

What type of bacteria does it act on?

A

Bactericidal - Synthetic broad spectrum

Targets DNA gyrase in gram negative bacteria and topoisomerase in gram positive bacteria

18
Q

What is the minimum inhibitory concentration ?

A

Lowest concentration of AB required to limit growth

19
Q

What are the four mechanisms for antibiotic resistance?

A

Altered target site - alternative gene or a gene that encodes a target modifying enzyme
Inactivation - enzymatic degradation or alteration makes the AB ineffective
Metabolism altered - increased production of substrate to out-compete or switch to other metabolic pathways
Drug accumulation - decrease drug accumulation - decreased permeability - increased efflux of AB

20
Q

What are the three sources of AB resistant genes?

A

Plasmids - extra-chromosomal circular dna - carry multiple AB resistance genes
Transposons - integrate into chromosomal DNA and allow transfer of genes from plasmid to chromosome and vice versa
Naked DNA - DNA from dead material released into the environment

21
Q

What are the three mechanisms for horizontal spread of AB resistance in bacteria?

A

Transformation - uptake of extracellular DNA
Conjugation - attach and out across DNA
Transduction - phage virus that infects bacteria, takes bacteria and passes it to another bacteria

22
Q

How do you get a high prevalence of AB resistant bacteria in the population?

A

Population contains cells with AB resistance due to mutations/acquired DNA – possibly with a fitness cost e.g. Slow growth

Presence of selection pressure

In presence of selection pressure (e.g. Abs) resistant mutants outcompete

High prevalence of AB resistant strains in patient population

23
Q

What are the effects of antibiotic resistance?

A

Second choice - second choice drug may be less effective
Time to effective therapy is increased
Additional approaches may be needed - eg surgery
Toxic drugs used more ie vancomycin
Expensive therapy - newer drugs may be more expensive
(STATE)

24
Q

What are the three mechanisms that can alter the target site in bacteria?

A

Change in target site structure

  • Mutation in gene encoding target site > change in peptide sequence > changes structure of target for AB
  • a target modifying enzyme gene is acquired

Alternate site - MRSA encodes an alternate penicillin binding protein which has a low affinity for beta lactams

Bacteria can produce enzymes that modify the AB target ie streptococcus pneumoniae via a gene which encodes an enzyme that methylates the AB target site in the 50s ribosomal subunit

25
Q

What are some non-genetic mechanisms of resistance/treatment failure?

A
Biofilm 
Intracellular location 
Slow growth 
Spores 
Persisters
26
Q

What are 5 reasons for treatment failure aside from Ab resistance?

A
Inappropriate choice for the organism 
poor penetration of AB into target site 
inappropriate dosage 
inappropriate adminstration
Presence of Ab resistance within commensal flora - ie secretion of beta-lactamase
27
Q

What are the risk factors for HAIs

A
Crowded wards
Antibiotic therapy
Broken skin
Devices (indwelling)
Ill and immunosuppressed patients
Pathogens present 
Staff in contact with multiple patients
28
Q

What harm can come about when AB therapy affects commensal flora?

A

Normally commensal flora outcompetes pathogens, if lack of commensal flora, pathogens has less competition and overgrows and produces toxins, damages host and can cause symptomatic infection

29
Q

What are 6 ways to overcome resistance?

A
Broad spectrum reduction 
Existing medication alteration 
Strategies of prescription 
Identifying infections quickly 
Combinations of Abs and inhibitors - ie augmentin 
Knowledge of local strains/patterns
30
Q

What Gram negative organism causes hospital acquired pneumonia, burn wounds, particularly affects immunocompromised hosts (e.g. chemotherapy, individuals with cystic fibrosis), and survives on abiotic surfaces?

A

pseudomonas aeruginosa