8. antimicrobial drugs and resistance

Question 1

these are agents used to treat diseases by destroying pathogenic microorganisms or inhibiting their growth at concentrations low enough to avoid undesirable damage to the host

Answer 1

antimicrobial agents

Question 2

in 1928 _______ was discovered

Answer 2

penicillin

Question 3

in 1935 ______ was discovered (not microbial produced)

Answer 3

sulfonamides

Question 4

in 1940, _______ was first used in clinical as an effective therapeutic substance

Answer 4

penicillin

Question 5

in 1944, _______ antibiotic was discovered from streptomycin bacterial species

Answer 5

streptomycin

Question 6

are antibiotics primary or secondary metabolites?

Answer 6

secondary

Question 7

today, 80% of the antibiotics are sourced from the bacterial genus ___________

Answer 7

streptomyces

Question 8

between what years were most antibiotics disordered

Answer 8

1950-1980

Question 9

do ideal antimicrobial drugs exhibit selective toxicity or non selective toxicity

Answer 9

selective toxicity

Question 10

this is when the drug is harmful to the pathogen and not the host

Answer 10

selective toxicity

Question 11

what are the 4 ways that a drug may act

Answer 11

1. inhibition of cell wall synthesis
2. inhibition of cell membrane function
3. inhibition of protein synthesis
4. inhibition of nucleic acid synthesis

Question 12

this is when the drug inhibits transpeptidation enzymes involved in the building of peptidoglycan layers of the cell wall by cross linking NAG and NAM; as a result
- incomplete cell wall build
- cell will lyse and die

Answer 12

inhibition of cell wall synthesis

Question 13

what are some drugs that are selective inhibitors of bacterial cell wall synthesis

Answer 13

• all beta-lactam antibiotics (penicillin, ampicillin, cephalosporins, cephamycin, carbapenems)
• vancomycin
• bacitracin
• novobiocin
• glycopeptide analogues (teicoplanin and cycloserine)

Question 14

after inhibiting the transpeptidation reaction, some of the beta-lactam drugs are involved in __________ which leads to cell wall lysis

Answer 14

the inactivation of inhibitors of autolytic enzymes in the cell wall

Question 15

T/F: gram positive and gram negative bacteria have different susceptibility to beta-lactam antibiotics due to structural differences in their cell walls

Answer 15

true

Question 16

why do beta-lactam drugs show a remarkable lack of toxicity to mammalian cells

Answer 16

our cells do not have cell walls which is what these drugs target!

Question 17

many pathogens gram positive and gram negative) show resistance to beta-lactam antibiotics due to their ability to produce __________: enzymes that inhibit or Destry beta-lactam compounds

Answer 17

beta-lactamases

Question 18

know some beta-lactamases that are plasmid-mediated

Answer 18

• penicillinase of staphylococcus aureus, neisseria gonorrhoeae. haemophilus influenzae, enterococci

Question 19

know some beta-lactamses that are chromosomally mediated

Answer 19

• bacteroids, acinetobacter, enterobacter, and pseudomonas species

Question 20

a group of beta-lactamses called _________________________ confer additional resistance to more beta-lactam drugs such as cefotaxime, ceftazidime, or aztreonam; produced by certain species of gram-negative bacilli

Answer 20

extended-spectrum beta-lactamases (ESBLs)

Question 21

ESBLs are produced by certain species of gram negative bacilli such as ____________ and __________

Answer 21

Klebsiella pneumoniae and Escherichia coli

Question 22

what are some examples of Beta-lactamase inhibitors?

Answer 22

clavulanic acid, sulbactam and tazobactam

Question 23

these have a high affinity for the beta-lactamses enzymes, they can bind to them and inhibit them rendering the beta-lactam resistant pathogen sensitive to beta-lactam drugs

Answer 23

beta-lactamase inhibitors

Question 24

what are some examples of B-lactam/B-lactamase inhibitors

Answer 24

-amoxicillin/clavulanic acid (augmentin)
-ampicillin/sulbactam (Unasyn)
-piperacillin/tazobacterum (zosyn)

Question 25

these drugs disrupt the membrane structure and permeability properties

Answer 25

polymyxins

Question 26

these drugs interfere with biosynthetic functions of the cell membrane and inhibit teichoic acid synthesis

Answer 26

nalidixic acid and novobiocin

Question 27

these drugs permit rapid diffusion of specific cations (such as potassium ions) through the membrane

Answer 27

ionophores (valinomycin)

Question 28

this drug is a rapid bactericidal; it binds to the cell and causes depolarization of the bacterial membrane. this leads to intracellular potassium release which causes cell death

Answer 28

daptomycin

Question 29

these drugs bind with the 30S subunit of the bacterial ribosome causing misreading of the mRNA and inhibiting protein synthesis

Answer 29

amuniglycosides (streptomycin and gentamicin)

Question 30

these drugs bind ti the 50S subunits and inhibit the chain elongation

Answer 30

macrolides, azalides, ketolides and lincoasmide
- erythromycin’s, azithromycin, clarithromycin and roxithromycin
- the ketolide telithromycin
- the lincosamide clindamycin

Question 31

these drugs binds reversibly to the 30S subunit of microbial ribosomes and interfere with aminoacyl-tRNA binding

Answer 31

tetracyclines

Question 32

this drug binds to the 50S subunit
it interferes with the binding of new amino acids to the nascent peptide chain, through inhibiting peptide transferase
this drug is mainly bacteriostatic

Answer 32

chloramphenicol

Question 33

these drugs possess a unique mechanism of inhibition of protein synthesis in gram positive bacteria
they interfere with translation by inhibiting the formation of N-formyl methionyl tRNA, the initiation complex at the 23S ribosome

Answer 33

oxazolidinones

Question 34

this was the first oxazolidinone to be commercially available, and it is used to treat infections caused by vancomycin-resistant Enterococci and even Mycobacterial infections

Answer 34

lienzolid

Question 35

this drug binds strongly to the DNA-dependant RNA polymerase of bacteria. it blocks bacterial RNA synthase

Answer 35

rifampin

Question 36

these drugs inhibit bacteria DNA gyrases (topoisomerase) thus interferes with DNA replication, transcription and DNA repair mechanisms

Answer 36

quinolones and fluoroquinolones

Question 37

these drugs inhibit the synthesis of nucleic acids

Answer 37

sulfonamides, trimethoprim and pyrimethamine

Question 38

_______ are produced by beta-lactam-antiobiotic-resistant pathogens e.g. K. pneumoniae, staphylococci

Answer 38

beta-lactamases

Question 39

__________ resistant pathogens produce adenylating, phosphorylating or acetylating enzymes that destroy the drug

Answer 39

aminoglycoside

Question 40

how can micro-organisms change their permeability to the drug?

Answer 40

through down regulation of porin channels require for B-lactan entry; exhibit resistance to carbapenam antibiotics based on the loss of these porin channel proteins

Question 41

_______ have a natural permeability barrier to aminoglycoside antibiotics

Answer 41

streptococci

Question 42

what are some examples where microorganisms can develop an altered structural target for the drug?

Answer 42

• modification in PBPs (mutation or expression of alternative PBPs): this can lower the ability of beta-lactam antibiotics to bind to PNPs in the bacterial cell wall
• erythromycin resistant organisms have an altered receptor on the 50S subunit of the ribosome

Question 43

in trimethoprim resistant bacteria, the dihydrofolic acid reductase (involved in nucleic acid synthesis) is inhibited far less efficiently than in trimethoprim susceptible bacteria. what is this an example of?

Answer 43

micro-organism can develop and altered enzyme that can still perform metabolic function but is much less affected by the drug

Question 44

this process occurs in some multi drug-resistant gram negative pathogens; the upregulation of efflux pumps in concert with low membrane permeability confers the resistance to penicillin and cephalosporins as well as other antibiotics

Answer 44

micro organisms develop efflux systems that expel antibiotics out of the cell