antimicrobials and resistance Flashcards

1
Q

What is the difference between endotoxins and exotoxins?

A

Endotoxins - Inflammatory response to bacterial products
Exotoxins - Response to bacterial secretions

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2
Q

what is a bacterial endotoxin

A

-released when organism dies
-triggers immune system
-heat stable, intrinsically poorly antigenic
-overactivates complement cascade to generate effects

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3
Q

what are the effects of bacterial endotoxin activating the complement cascade

A

-high fever
-severe fluid from blood system–> vascular collapse
-IV coagulation then organ haemorrhaging
-septicaemia/endotoxic shock–> death

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4
Q

what are the factors facilitating entry/invasion/survival of bacterial exotoxins

A

-mucinase, collagenase, urease, leukocidins etc

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5
Q

what are antimicrobial agents

A

-inhibit/kill microorganisms
-99% unsuitable for treatment of infectious diseases- e.g. disinfectants, antiseptics
-<1% suitable for treatment= chemotherapeutic agents

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6
Q

what is the mark of a successful CTA

A

-its selective toxicity i.e. toxicity to prokaryotes»>toxicity to eukaryotes

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7
Q

what is a therapeutic dose

A

-level of CTA needed for clinical treatment of an infection in a specific host

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8
Q

what is a toxic dose

A

level of same CTA which is too toxic for use in that host

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9
Q

therapeutic index=

A

toxic dose/therapeutic dose
High- selectively toxic, useful
Low - toxic to host, side effects

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10
Q

what do bacteriostatic CTAs do

A

-inhibit bacterial growth/multiplication but then reply on the hosts immune system to remove the bugs
-it is therefore essential to give full course of such agents to allow sufficient time for immune system to complete its job whilst preventing regrowth of the bacterial population

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11
Q

what are bactericidal CTAs

A

rapidly lethal to the bacteria in their own right

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12
Q

depending on bug and conditions, some agents may be…

A

bactericidal and bacteriostatic e.g. chloramphenicol kills H.influenzae but only inhibits E.coli

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13
Q

what are the mechanisms of action of antibiotics

A
  1. Inhibition of cell wall synthesis
  2. inhibition of protein synthesis
  3. Inhibition of nucleic acid
  4. impair membrane functions
  5. metabolic antagonism
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14
Q

what are the antibiotics that inhibit cell wall synthesis

A

cycloserine
glycopeptides- bacitracin
beta-lactams e.g. penicillins and cephalosporins

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15
Q

what are the antibiotics involved in inhibition of protein synthesis

A

aminoglycosides
tetracyclines
chloramphenicol

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16
Q

what are the antibiotics involved in inhibiting nucleic acid synthesis

A

quinolones
rifampin

17
Q

what is metabolic antagonism

A

-CTAs are structural but not functional analogues of bacterial growth factors
-not functional when bacteria tries to put it into macromolecules its making
-bactericidal
-selectively toxic

18
Q

What are the mechanisms of bacterial resistance

A
  1. production of enzymes- attack CTA, prevent activity or degrade CTA
  2. modify CTAs target- as produced or after production. must be a sublethal change
  3. alter CTA uptake/retention- no entry to cell. upregulate removal»>uptake
  4. upregulate target production- dilute out effect of CTA
  5. modify metabolic pathways
  6. cross resistance
19
Q

what do bacteria release to digest CTA

A

-beta lactamase inactivates beta-lactam agents
-acetyltransferase inactivates chlroamphenicol

20
Q

What CTA targets can mutate to increase resistance?

A

-23S protein of the 50S ribosomal subunit
-30S ribosomal subunit
-DNA-dependent RNA-polymerase
-DNA gyrase
-dihydropteroate synthetase

21
Q

How can bacterium alter the uptake of CTAs

A

-enhance existing permeability barrier
-alter/remove specific transport system
-develop specific antagonism

22
Q

What are cross-reactive agents

A

-ESBLs- extended spectrum beta lactamases
-metallo beta lactamases

23
Q

what are the methods of development of resistance

A

-spontaneous mutation
-recombination

24
Q

how does spontaneous mutation lead to CTA resistance under normal conditions

A

CTA resistance lost by back mutation or overgrowth by S bacteria

25
Q

how does spontaneous mutation lead to CTA resistance during treatment

A

resistant clone selected