Microbiology Chapter 5: Biological Basis For Antimicrobial Action

Front 1

What substance do sulfanilamide drugs resemble? What happens when the drugs are introduced?

Back 1

p-aminobenzoic acid a component of folic acid. They bind with dihydropteroic acid instead of p-aminobenzoic acid. The product is lethal

Front 2

Enough p-aminobenzoic acid be added to overcome the sulfonamides. What type of antagonism is occuring here?

Back 2

competitive inhibition

Front 3

What is p-aminobenzoic acid a constituent of?

Back 3

folic acid

Front 4

What happens to the production of nucleosides and amino acids when a sulfa drug is used?

Back 4

Their synthesis decreases becuase THFA is needed to add carbons to precursors for amino acids and necleosides

Front 5

How does folic acid in contrast to p-aminobenzoic acid inhibit sulfa drugs?

Back 5

noncompetitively

Front 6

Why is it that some bacteria even when supplemented with folic acid are still susceptible to sulfa drugs?

Back 6

They are adept at making folic acid and not importing it

Front 7

How long will cessation of bacterial growth take after a sulfa drug is administered and why?

Back 7

2-4 generations can form because there is a residual of folic acid

Front 8

If a patient has bacterial endocarditis would you administer a bactericidal drug or a bacteriostatic drug?

Back 8

Bacteriocidal agents because this is a case when drugs are more adept at killing the organism than the immune system. Other times when this would hold is in someone with agranulocytopenia and meningitis

Front 9

What would be a case when you would want to give someone a bacteriostatic drug over a bactericidal drug?

Back 9

If the infecting organism is producing a toxin and you want to prevent it from producing more. This gives the immune system more time to eradicate the bacteria. Bactericidal drugs would not inhibit organism for a few generations allowing them to produce toxin for hours to days longer

Front 10

What is an example of a drug that is static in one organism but cidal in another?

Back 10

The aminoglycoside spectinomycin is static for E. coli but cidal for gonococci

Front 11

How is that a drug may be cidal for 99% of bacteria during an infection but static for the remaining bacteria?

Back 11

The bacteria that appear to be resistant may be in a particular growth phase where they are not susceptible or they may have acquired a beneficial mutation or plasmid to make them resistant

Front 12

How could you circumvent the problem of a drug being only partially cidal to infecting bacteria?

Back 12

Add a second drug

Front 13

What are a couple of factors that limit microbial sensitivity, give a few examples?

Back 13

environmental factors, for example aminoglycosides poorly affect bacteria in anearobic conditions. Drug availability also effects sensitivity, in that it may be difficult to deliver to the site of infection.

Front 14

Name a drug that does not effect anaerobic bacteria?

Back 14

aminoglcyosides

Front 15

Why is nitrofurantoin good for urinary tract infections but not for organisms infecting the blood?

Back 15

It is concentrated in the urine and has limited reabsorption therefore it does not reach high enough blood levels to be effective

Front 16

A drug with a large dosing gap between its effective and toxic dose has a ______?

Back 16

high therapeutic index

Front 17

What type of antimicrobial adminsitration technique is likely to have fewer side effects?

Back 17

Generally topical drugs or drugs that may not be absorbed through the GI tract

Front 18

Does trimethoprim block the synthesis or function of folic acid? What is the drugs MOA?

Back 18

The function of folic acid. Inhibit dihydrofolate reductase which catalyzes the reduction of dihydrofolate to tetrahydrofolate

Front 19

Why is trimethoprim not active against human dihydrofolate reductase?

Back 19

It is needed in much higher concentrations to inhibit the human enzyme. This may be due to the human enzyme having a higher dissociation constant (Km) for trimethoprim

Front 20

What organisms can trimethoprim be used to treat?

Back 20

Certain bacteria and protozoa

Front 21

Name an antibiotic that is more effectively concentrated in bacteria and as a result can be used against intracellular bacteria like chlamydia?

Back 21

tetracyclines, note that they are harmful to both host and pathogen

Front 22

What is the mode of resistance to penicillins/cephalosporins?

Back 22

beta-lactamase gene encoded on plasmid

Front 23

What is the mode of resistance to methicillin?

Back 23

a change in penicillin-binding protein. Most likely a genomic mutation since it is not from a plasmid

Front 24

What is the mode of resistance to tetracyclines?

Back 24

efflux pump gene encoded on plasmid

Front 25

What is the mode of resistance to aminoglycosides?

Back 25

R plasmid encoded enzyme modifies drug thus drugs binding affinity decreases and so does its transport into cells

Front 26

What is the mode of resistance to sulfonamides?

Back 26

Sulfanilamide-resistant dihydropteroate synthase plasmid gene

Front 27

What is the mode of resistance to trimethoprim?

Back 27

Trimethoprim-resistant dihydrofolate reductase plasmid gene

Front 28

What is the mode of resistance to erythromycin?

Back 28

plasmid coded enzyme that methylates 23S rRNA

Front 29

What is the mode of resistance to chloramphenicol?

Back 29

chloramphenicol transacetylase plasmid gene. Enzyme hydroxylates drug preventing translocation into cell

Front 30

What is the mode of resistance to oxazolidinones?

Back 30

Genomic mutations in 23S rRNA

Front 31

What drug is in the oxazolidinones?
What is its MOA?

Back 31

Linezolid- inhibits protein synthesis by preventing formation of ribosome complex. Binding site is on 23S rRNA of 50S subunit

Front 32

What is the mode of resistance to quinolones?

Back 32

genomic mutation of the DNA gyrase and topoisomerase IV genes

Front 33

What is the mode of resistance to vancomycin?

Back 33

Change in the binding site of peptidoglycan target. Plasmid derived

Front 34

What do 3rd generation cephalosporins offer that older versions do not?

Back 34

They are effective against organisms like pseudomonas and haemophilus influenzae which were resistant to previous generations. They can also penetrate the CNS

Front 35

What type of infection is pseudomonas?

Back 35

oppurtunistic

Front 36

What are the 2 types of beta-lactamases

Back 36

penicllinases and cephalosporinases

Front 37

Where do the beta-lactamases of gram+ and - work?

Back 37

gram+ work in the extracellular space and the gram- enzymes work free-floating in the periplasm or bound to the inner membrane

Front 38

Can heavier doses of beta-lactams be more effective against gram- or gram+?

Back 38

gram- because they produce beta-lactamase at a constant rate and therefore the drug can overwhelm the beta-lactamase production

Front 39

Most gram- bacteria are resistant to beta-lactams except?

Back 39

gonococcuss is still susceptible to penicillin G

Front 40

What is the mode of transmission that is leading to gonococcus resistance of beta-lactams?

Back 40

transposons- they are fragments of DNA that are able to insert themselves into the genome of organisms. This resistance is being spread to gram- aerobics

Front 41

What is the difference in methicillin resistance occurring between gram - and gram+ bacteria?

Back 41

gram- bacteria alter the porin in the outer membrane that transports the drug into the periplasm whereas gram+ bacteria undergo genomic mutations to alter the penicillin binding proteins so that they do not bind beta-lactams

Front 42

Why is S. aureus in particular so resistant to beta-lactams?

Back 42

Not only do they have a beta-lactamase but they also have developed a penicillin binding protein mutation making them resistant to methicillin

Front 43

What antibiotics might be effective in treating MRSA?

Back 43

vancomycin, linezoid or daptomycin

Front 44

What happens to bactericidal drugs with tolerance?

Back 44

They become bacteriostatic. This has happened in pneumococci that lack sufficient autolysin

Front 45

List some mechanisms that could explain relapse?

Back 45

Tolerance, bacteria in various stages of growth, not finishing antibiotics

Front 46

What antibiotic is commonly given IV to hospitalized patients with a gram+ infection?

Back 46

vancomycin

Front 47

What changes to make bacteria resistant to vancomycin? What bacteria is this primarily occurring in?

Back 47

Terminal D-alanine-D-alanine goes to D-alanine-D-lactate. Enterococcus

Front 48

Why is vancomycin resistant enterococcus extremely difficult to treat?

Back 48

they generally are also resistant to beta-lactams and aminoglycosides

Front 49

How do quinolones kill bacteria?

Back 49

They trap topoisomerases in the act of cutting DNA and result in double stranded DNA breaks

Front 50

Are fluoroquinolones effective against both gram- and gram+ bacteria?

Back 50

yes

Front 51

Flouroquinolone resistance generally occurs through topoisomerase gene mutations, what mechanism is now conveying resistance?

Back 51

efflux pump, seen in gram- pseudomonas and gram+ staph a.

Front 52

What side effects are seen in people taking tetracyclines? aminoglycosides?

Back 52

chelation of Mg resulting in bone and tooth malformation in children. toxicity in the renal tubules and inner ear

Front 53

What is the difference between aminoglycoside uptake and tetracycline?

Back 53

They both involve a two-stage transport system but tetracycline is reversible and can be pumped out

Front 54

What organisms have been found to be resistant to tetracyclines?

Back 54

Almost all organisms including gram+, gram-, aerobes and anaerobes

Front 55

What is the main mechanism of resistance to macrolides?

Back 55

efflux pumps and they have a methylase plasmid gene that blocks the 23S ribosome with a methyl group

Front 56

What macrolide binds at two sites on the 23S ribosome and remains effective when the methylase containing plasmid is present?

Back 56

telithromycin

Front 57

Where have mutations occurred that are rendering resistance to the synthetic drug linezolid?

Back 57

on the 23S RNA

Front 58

What do the imidazoles target?

Back 58

cytochrome P450 demethylase involved in sterol synthesis

Front 59

What is the mutation rate pertaining to antibiotic resistance?

Back 59

1 per 10^6-10^9 per generation

Front 60

A patient is being treated with multiple drugs. The mutation rate of the first drug is 10^3 and the second is 10^11. What is the chance that the organism will be resistant to both drugs?

Back 60

1 in 10^14

Front 61

Define drug synergysm

Back 61

the effect of both drugs complement each other and are more effective than either alone

Front 62

Give an example of synergism!

Back 62

enterococci are resistant to penicillins and gentamycin, however when given together penicillin allows gentamicin to enter the cell and has a bacteriocidal effect in the cytoplasm

Front 63

What is an example of antagonism?

Back 63

giving a bacteriostatic drug like tetracycline and a bactericidal drug like penicillin

Front 64

What is drug indifference?

Back 64

neither drug aids or inhibits the others action