antibiotics symposium Flashcards

1
Q

what is an antibiotic?

A

agents produced by micro-organisms that kill or inhibit the growth of other micro-organisms in high dilution

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2
Q

how do antibiotics work?

A

by binding a target site on a bacteria
this crucial binding site will vary with the antibiotic class

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3
Q

what are antimicrobials?

A

semi-synthetic derivatives of antibiotics
Defined as points of biochemical reaction crucial to the survival of the bacterium
HOWEVER IN PRACTISE
ANTIBIOTIC= ANTIBRACTERIAL

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4
Q

give examples of antimicrobials

A

antifungal, antibacterial, antihelminthic,
antiprotozoal and antiviral agents

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5
Q

what do beta lactam antibiotics do ?

A

disrupt peptidoglycan production by binding convalently and irreversibly to the penicillin binding proteins- causing cell Wass to disrupt-lysis occurs- resulting in hypo-osmotic or iso-osmotic environment

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6
Q

what are beta lactic antibodies active against?

A

only rapidly multiplying organisms

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7
Q

in order to bind to the penicillin binding proteins, what must the beta lactam antibodies do first?

A

diffuse through the bacterial wall

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8
Q

what do gram negative organisms have that decreases antibiotic penetration?

A

an additional lipopolysaccharide layer

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9
Q

what are the differences in the activity of beta lactam antibodies due to?

A

their relative affinity for different Penicillin Binding Proteins

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10
Q

why are beta lactams innefective in the treatment of intracellular pathogens?

A

because penicillins poorly penetrate mamlilan cells

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11
Q

describe the bacterial agenda

A
  1. attach and enter
  2. local spread
  3. multiply
  4. evade host defences
  5. shed from body
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12
Q

what are the direct consequences of bacteria?

A

destroy phagocytes or cells in which bacteria replicate

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13
Q

what are the indirect consequences of bacteria?

A

inflammation- e.g necrotic cells
immune-pathology- e.g antibody

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14
Q

what are the toxin related consequences of bacteria?

A

Exotoxin - Protein production
Endotoxin - Gram negative

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15
Q

what are bactericidal antibiotics?

A

agents that kill the bacteria
are antibiotics that inhibit cell wall synthesis

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16
Q

when are bactericidal antibiotics useful?

A

Useful if poor penetration (Endocarditis),
when it is difficult to treat infections or need to eradicate infection quickly (meningitis)

17
Q

define bacteriostatic antibodies

A

defined as a ratio of Minimum Bactericidal Concentration (MBC) to Minimum inhibitory Concentration (MIC) of > 4
Antibiotics that Inhibit protein synthesis, DNA replication or metabolism

18
Q

what do bacteriostatic antibodies do?

A

Reduce toxin production and Endotoxin surge less likely
they prevent growth of bacteria

19
Q

what are the two major detriments of anti bacterial effects?

A

concentration
time
( that the antibiotic remains on these binding sites

20
Q

what does the antibiotic drug do?

A

drug must not only attach to its binding target but also must occupy an adequate number of binding sites, which is related to its concentration within the microorganism.

21
Q

in order to work effectively what does the antibiotic have to do?

A

the antibiotic should remain at the binding site for a sufficient period of time in order for the metabolic processes of the bacteria to be sufficiently inhibited.

22
Q

describe time dependent killing

A

Key parameter is the time that serum concentrations remain above the MIC during the dosing interval
t>MIC

23
Q

describe concentration dependant killing

A

Key parameter is how high the concentration is above MIC
peak concentration/MIC ratio

24
Q

what is the antibiotic dependant on?

A

pharmokinetics- The movement of a drug from its administration site to the place of its pharmacologic activity and then its elimination from the body

25
how do bacteria resist antibiotics?
- change antibiotic target - destroy antibiotic -prevent antibiotic access -remove antibiotic from bacteria
26
resist antibiotics-describe change antibiotic target
Bacteria change the molecular configuration of antibiotic binding site or masks it e.g- Flucloxacillin (or methicillin) is no longer able to bind PBP of Staphylococci – MRSA* Wall components change in enterococci and reduce vancomycin binding – VRE# Rifampicin activity reduced by changes to RNA polymerase in MTB – MDR-TB$
27
resist antibiotics-describe destroy antibiotic
The antibiotic is destroyed or inactivated e.g. Beta lactam ring of Penicillins and cephalosproins hydrolysed by bacterial enzyme ‘Beta lactamase’ now unable to bind PBP
28
resist antibiotics-describe-prevent antibiotic access
modify the bacterial membrane porin channel size, numbers and selectivity e.g. -Pseudomonas aeruginosa against imipenem, -Gram negative bacteria against aminoglycosides
29
resist antibiotics-describe-remove antibiotic from bacteria
Proteins in bacterial membranes act as an export or efflux pumps - so level of antibiotic is reduced
30
why do bacteria develop resistance?
intrinsic- naturally resistant acquired- spontaneous gene mutation -horizontal gene transfer- conjugation -transduction -transformation
31
intrinsic resistance
All subpopulations of a species will be equally resistant e.g. Aerobic bacteria are unable to reduce metronidazole to its active form -Vancomycin cannot penetrate outer membrane of gram negative bacteria
32
acquired resistance
A bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic Only certain strains or subpopulations of a species will be resistant
33
name two Important resistances in Gram positive bacteria
MRSA VRE
34
describe MRSA
Methicillin resistant Staphylococcus aureus Bacteriophage mediated acquisition of Staphylococcal cassette chromosome mec (SCCmec) contains resistance gene mecA encodes penicillin-binding protein 2a (PBP2a) confers resistance to all β-lactam antibiotics in addition to methicillin (= flucloxacillin)
35
describe VRE
vancomycin-resistant enterococci Plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding Promoted by cephalosporin use
36
Name an important resistance in Gram-negative bacteria
ESBL
37
describe ESBL
extended spectrum beta lactamase (ESBL) inhibition These hydrolise oxyimino side chains of cephalosporins: cefotaxime, ceftriaxone, and ceftazidime and monobactams: aztreonam