ICL 2.26: Intro to Antibiotics

Question 1

what are antimicrobial drugs?

Answer 1

they’re chemicals used to treat microbial infections

before antimicrobials, large number of people died from common illnesses

now many illnesses are easily treated with antimicrobials

Question 2

what are the characteristics of an ideal antibiotic?

Answer 2

1. broad-spectrum
2. favorable pharmacokinetics = reach target site in body with effective concentration
3. preserve normal microbial flora
4. does not induce resistance
5. selective toxicity -low side effects

Question 3

what is selective toxicity?

Answer 3

cause greater harm to microorganisms than to host

so it’s the balance between efficacy and toxicity

Question 4

what is the chemotherapeutic index?

Answer 4

lowest dose toxic to patient divided by dose typically used for therapy

chemotherapeutic index = toxic dose/therapeutic dose

Question 5

what does bacteriostatic mean?

Answer 5

inhibit growth of microorganisms

static antibiotics allow the immune system the time to eliminate the infecting agent

Question 6

what does bactericidal mean?

Answer 6

kills microorganisms

Question 7

what patient population can’t be treated with static antibiotics?

Answer 7

1. immunodeficient patients with acute infections

2. patients with infections in immunologically privileged sites

Question 8

what is the spectrum of activity of an antibiotic drug?

Answer 8

antimicrobial medications vary with respect to the range of microorganisms they kill or inhibit

1. narrow-spectrum antimicrobials = kill only limited range
2. broad-spectrum antimicrobials = kill wide range of microorganisms

Question 9

what is the tube dilution method of the susceptibility test?

Answer 9

Minimum inhibitory concentration (MIC) = lowest concentration of antibiotic that inhibits visible growth

Minimum bactericidal concentration (MBC) = lowest concentration of antibiotic that kills 99.9% of the inoculum

Question 10

what is the disk diffusion method of the susceptibility test?

Answer 10

Zone of inhibition (ZOI) = the correlation of ZOI and MIC has been established by FDA

MIC = lowest concentration of antibiotic that inhibits visible growth

Question 11

what are the different mechanisms of action of antibacterial drugs?

Answer 11

1. inhibit cell wall synthesis
2. inhibit protein synthesis
3. inhibit nucleic acid synthesis
4. injury to plasma membrane
5. inhibit synthesis of essential metabolites

Question 12

which antibiotics inhibit cell wall synthesis?

Answer 12

1. penicillins
2. cephalosporins
3. vancomycin

Question 13

what does polymyxin B do?

Answer 13

binds to membrane of gram (-) bacteria and alters permeability

this leads to leakage of cellular contents and cell death

these drugs also bind to eukaryotic cells to some extent, which limits their use to topical applications

Question 14

which antibiotics inhibit nucleic acid synthesis?

Answer 14

1. fluoroquinolones

2. rifampin

Question 15

what do fluoroquinolones do?

Answer 15

antibiotic that inhibits nucleic acid synthesis

it inhibits enzymes that maintain the supercoiling of closed circular DNA

Question 16

what does rifampin do?

Answer 16

antibiotic that inhibits nucleic acid synthesis

it blocks prokaryotic RNA polymerase from initiating transcription

Question 17

how do antibiotics that inhibit synthesis of metabolites work?

Answer 17

competitive inhibition by substance that resembles normal substrate of enzyme

ex. sulfa drugs

Question 18

how do antibiotics that inhibit protein synthesis work?

Answer 18

they target the ribosomes of bacteria

Question 19

which antibiotics inhibit protein synthesis?

Answer 19

1. tetracyclines
2. chloramphenicol
3. aminoglycosides

Question 20

what do tetracyclines do?

Answer 20

they inhibit protein synthesis by binding to 30S subunit of bacterial ribosomes and blocking attachment of tRNA

Question 21

what does chloramphenicol do?

Answer 21

it inhibits protein synthesis by binding to 50S subunit and prevents continuation of protein synthesis

Question 22

what do aminoglycosides do?

Answer 22

they inhibit protein synthesis by binding to 30S subunit causing it to distort and malfunction; blocks initiation of translation

Question 23

what is synergism?

Answer 23

combining drugs that work together

antibiotic combination is four or more times as great as the sum of their individual effects

Question 24

how do penicillin + aminoglycoside create synergism?

Answer 24

aminoglycosides do not get across the cell wall very good

but penicillin weakens the cell wall barrier and allows better penetration

this allows small amounts of the relatively toxic aminoglycoside to be used

Question 25

what are antagonistic effects?

Answer 25

drug combinations that work against each other

Question 26

how are penicillin and chloramphenicol antagonistic?

Answer 26

penicillin inhibits cell wall synthesis which requires rapidly growing bacteria

chloramphenicol on the otherhand is bacteriostatic so it stops the multiplication and stops the need for cell wall synthesis

this makes penicillin irrelevant…

Question 27

what is the benefit of multiple-drug therapy?

Answer 27

1. prevents the onset of disease in immunosuppressed or debilitated patients
2. empirical therapy when the specific agent of disease is unknown
3. treat infections that involve more than one bacterial species
4. treat infections caused by bacteria that are difficult to eradicate
5. to treat chronic diseases in which bacteria may develop resistance to an antibiotic during the course of therapy

Question 28

what is natural vs. acquired resistance?

Answer 28

natural resistance = structural barrier, transport system, lack of target

acquired resistance = mutation, gene exhange etc.

Question 29

what are some instances of overuse/misuse of antibiotics?

Answer 29

1. Prophylactic use before surgery
2. Empirical use (blinded use)
3. Increased use of broad spectrum agent
4. Pediatric use for viral infections
5. Patients who do not complete the course (chronic disease, eg. TB, AIDS)
6. Antibiotics in animal feeds

Question 30

what’s the problem with overuse/misuse of antibiotics?

Answer 30

bacterial resistance!!

Question 31

what is the clinical significance of antibiotic resistance?

Answer 31

1. therapeutic failures and relapse
2. facilitates spread in the hospital under “antibiotic pressure”
3. eed to use more costly and toxic agents
4. the emergence of untreatable pathogens