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Medsci 202 > Lecture 13 - antibiotics > Flashcards

Lecture 13 - antibiotics Flashcards

1
Q

define Antibiotic

A

substance produced by a microorganism that is effective in killing or inhibiting growth of other microorganisms.

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2
Q

define an Antimicrobial agent

A

any chemical drug used to treat an infectious disease

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3
Q

describe the types of Antimicrobial agent

A
  • antibacterial agent
  • antifungal agent
  • antiprotozoal agent
  • antiviral agent
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4
Q

what are the three origins of antibiotics?

A

Organic
Semi-synthetic
Synthetic

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5
Q

Describe the organic origin of antibiotics

A

isolated from bacteria or fungi (e.g., penicillin, erythromycin)

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6
Q

Describe the semi-synthetic origin of antibiotics

A

urther derivatisation of organic compound for

greater efficacy, e.g. ampicillin

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7
Q

Describe the synthethic origin of antibiotics

A

generated in the lab (e.g. sulfonamides

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8
Q

What are the Ideal qualities of an antibiotic

A
  • kill or inhibit growth of pathogens
  • cause no damage to the host
  • cause no allergic reaction to the host
  • be stable for storage as solid or liquid
  • remain in specific tissue long enough to be effective • kill the pathogens before they mutate and become resistant
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9
Q

Define antibacterial spectrum

A

range of activity against bacteria, e.g. broad or narrow

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10
Q

define narrow spectrum

A

only against a limited variety of bacteria e.g. vancomycin (only against gram-positives)

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11
Q

define broad spectrum

A

against a variety of Gram+/- bacteria e.g. ampicillin

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12
Q

Define bacteriostatic activity

A

level of antimicrobial activity that inhibits growth of organism.

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13
Q

define bacteriocidal activity

A

level of antimicrobial activity that kills organism.

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14
Q

define antibiotic combination

A

combining different antibiotics for:

  • broaden the antimicrobial spectrum
  • treatment of polymicrobial infections
  • prevent emergence of resistant organism - achieve a synergistic killing effect
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15
Q

define antibiotic antagonism

A

activity of one antibiotic interferes with activity of other, e.g.
the sum of activity is less then the most active individual drug (penicillin-chloramphenicol)

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16
Q

define antibiotic synergism

A

enhanced antimicrobial activity of combined drugs compared to activity of each individual antibiotic (penicillin-streptomycin)

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17
Q

what is an antibiogram

A

result of lab testing for sensitivity of an isolated strain to different antibiotics

18
Q

name three types of antibiograms

A
  1. Semi-quantitative based on diffusion (Kirby-Bauer method)
  2. Quantitative based on dilution series
  3. Determining the Minimum Bacteriocidal Concentration (MBC)
19
Q

define Semi-quantitative based on diffusion (Kirby-Bauer method)

A

Antibiotic concentration highest at centre of disc and lowest at edges. The Minimum Inhibitory Concentration (MIC) can be calculated from the diameter.

20
Q

define Quantitative based on dilution series

A

The last vial in which no bacteria grow contains antibiotic at Minimum Inhibitory Concentration (MIC)

21
Q

define Determining the Minimum Bacteriocidal Concentration (MBC)

A

subculturing the clear broth onto antibiotic-free solid media
MBC = reduction of colony forming units (CFU) by 99.9% below control.

22
Q

What are the basic sites of antibiotic activity?

A
  1. cell wall synthesis
  2. Rna synthesis
  3. DNA rep
  4. antimetabolites
  5. protein synthesis - 50s ribosome
  6. protein synthesis - 30s ribosome
23
Q

Explaim how beta lactam antibiotics work?

A

a. β-lactam antibiotics: - penicillins (from Penicillium) - cephalosporins (from Acremonium) - carbapenems
- inhibit peptidoglycan synthesis by irreversible inhibition of peptidyl transferase (=penicillin binding protein, PBP)
weak cell wall and osmotic lysis - bactericidal
- PG is unique to bacteria !!

24
Q

What are gram nagative bacteria reseistant to? how does penicillin work?

A

Penicillin does not pass through outer membrane porins - extended spectrum penicillins (amoxicillin, ampicillin, …)
- semi-synthetic

25
Q

What types of antibiotics affect beta lactamases? describe beta lactamases

A

Penicillinase Cephalosporinase

β-lactamases are plasmid encoded enzymes that can be transferred between bacterial strains and species.

26
Q

what are β-lactamase resistant penicillins

A
  • methicillin, oxacillin, flucloxacillinthese are unaffected by β-lactamase
    Clavulanic acid: β-lactamase inhibitor Augmentin = ampicillin + clavulanic acid
27
Q

what are Drugs that block bacterial cell wall synthesis

A

b. Glycopeptides: Vancomycin
- inhibits PG synthesis by binding to the peptides of the peptidoglycan monomers.
* weak cell wall and osmotic lysis
- mainly against gram-positives
- drug of “last resort” , e.g. for MRSA
- bactericidal

28
Q

what are Inhibitors of RNA transcription

A

a. Rifamycins
- inhibit bacterial RNA polymerase, e.g. Rifampin (Rifampicin)
- typically used against Mycobacteria (e.g. tuberculosis, leprosy), MRSA, bactericidal

29
Q

what are Inhibitors of nucleic acid synthesis

A

Quinolones and Fluoroquinolones (synthetic)

  • bind DNA topoisomerases (enzymes needed for supercoiling, replication and separation of circular bacterial DNA), e.g. gyrase, topoisomerase IV, helicase
  • prevent DNA supercoiling, broad spectrum, bactericidal - commonly used against urinary tract infections.

Nalidixic acid (Q) Ciprofloxacin (FQ)

30
Q

what are Antimetabolites

A

a. Sulfonamides
- analogues of PABA, competitively inhibits pteridine synthase
b. Trimethoprim
- inhibits bacterial dihydrofolate reductase (DHFR)
Both antibiotics block pathway required for the synthesis of tetrahydrofolic acid, a cofactor needed to make nucleic acids.
mammalian cells depend on external folate (B9)
- bacteriostatic,
- used against e.g. urinary tract infections

31
Q

What are Inhibition of protein synthesis

a) by binding to the 30S subunit

A

Aminoglycosides: e.g. neomycin, gentamycin, kanamycin

  • freeze the 30S initiation complex (30S-mRNA-tRNA)
  • misreading of DNA due to frame-shifts
  • mostly effective against aerobic, gram-negative bacteria, bactericidal
  • synergistic with penicillins
32
Q

What are Inhibition of protein synthesis

a) by binding to the 30S subunit - Tetracyclines (tetracycline, doxycycline)

A
  • inhibit binding of aminoacyl-t-RNA to the acceptor site on the ribosome.
  • broad-spectrum, bacteriostatic, used against many bacterial infections
33
Q

What are Inhibition of protein synthesis

b) by binding to the 50S subunit

A

Macrolides, e.g. erythromycin
- inhibit translocation of the peptidyl tRNA from the A to the P site - against gram-positives, Mycoplasma, bacteriostatic

Chloramphenicol
- broad-spectrum, bacteriostatic
- toxic, used against bacterial meningitis

34
Q

Describe Antibiotic resistance

1. Non-genetic (intrinsic) drug resistance

A

a. Metabolic inactivity
most drugs only effect metabolically active cells, not dormant cells

b. Lack of target structure
Mycoplasmas lack cell wall (resistance to penicillins, cephalosporin, vancomycin)

c. Exclusion
antibiotic can’t enter cell (e.g. penicillin/Gram-negative bacteria)

35
Q

Describe Antibiotic resistance - Genetic resistance

A

a. Chromosomal resistance
- spontaneous mutation in a gene encoding a target receptor: mutation of RNA- polymerase gene results in rifamycin resistance.

b. acquired resistance

36
Q

What is Selection for antibiotic resistant strains

A

survival of the fittest

37
Q

Describe 6 ways of Antibiotic resistance mechanisms

A
  1. Exclusion of antibiotic from site of action
  2. Efflux pump for the antibiotic removal from site of action
  3. Enzymatic modification
  4. Destruction
    -β-lactamase
  5. Modified antibiotic insensitive target
  6. New antibiotic-insensitive target
    alternative PBP
38
Q

what are the two types of drug resistance?

A

Multidrug-resistant strains: resistant to more than one class of drugs Pandrug-resistant strains: resistant to all clinically safe drugs

39
Q

What is Methicillin-resistant S. aureus (MRSA) resistant to?

A

resistant to all antistaphylococcal drugs, except Vancomycin

40
Q

what is Vancomycin-intermediate S. aureus (VISA) resistant to?

A

resistant to usual dosage of vancomycin

41
Q

what is Vancomycin-resistant S. aureus (VRSA) resistant to?

A

resistant against all antistaphylococcal drugs

42
Q

what is the full form of VREn and MRTB

A
  • Vancomycin-resistant Enterococcus (VRE)

* Multidrug-resistant Mycobacterium tuberculosis (MRTB)

Medsci 202 (15 decks)

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