L20: Antibiotics

Question 1

Bacteriostatic

Answer 1

Inhibit growth (don’t kill bacteria) – used when host defense can be counted on

Question 2

Bactericidal

Answer 2

Kill bacteria – used for invasive bacteria (ex. bacteremia, meningitis, endocarditis) or for immunocompromised patients

Question 3

Antibiotic synergism

Answer 3

Combination of two antibiotics with enhanced bactericidal activity when used together

Question 4

Antibiotic antagonism

Answer 4

Combination of antibiotics in which one interferes with the activity of the other

Question 5

Broad-spectrum antibiotic

Answer 5

Effective against a large variety of bacteria; used in emergency situation when lab results are not available but might have consequences due to interrupting normal microbiota

Question 6

Narrow-spectrum antibiotic

Answer 6

Effective against only a small subset of bacteria; used when specific disease-causing agent is known, avoids disruption of the normal microbiota

Question 7

Principles of rational and effective antibiotic use

Answer 7

• -Only for bacterial infections
• -Important to collect representative sample before therapy
• -Empiric therapy followed by targeted therapy
• -Adjustments if needed

Question 8

How can we help stop antibiotic resistance?

Answer 8

• -Prescribe the right antibiotics
• -Make sure patients take the whole course
• -Use combinatorial therapy
• -Antibiotic prophylaxis – prevents rather than treats disease (for any immunocompromised or surgical patients and exposure to certain bacteria)

Question 9

General mechanisms of antimicrobial resistance

Answer 9

–Breakdown of antibiotic by hydrolysis
–Chemical modification of an antibiotic
–Alteration of the target
by mutations/gene acquisition
–Altered permeability, decreased influx or increased efflux
–Lack of target

Question 10

Minimum inhibitory concentration (MIC)

Answer 10

Lowest concentration of antibiotic that inhibits growth

Question 11

Minimum bactericidal concentration (MBC)

Answer 11

Lowest concentration of antibiotic that kills 99.9%

Question 12

Kirby-Bauer test (disc-diffusion assay)

Answer 12

A antimicrobial agent is placed on a plate and bacteria is tested to see how it goes (grows on top of disc = resistant); measures MIC

Question 13

E-test

Answer 13

Measures MIC with strips to see what concentration is needed

Question 14

Broth-based method

Answer 14

Can see where MIC/MBC are based on concentration of cultures

Question 15

Mechanisms of action

Answer 15

• -Cell wall synthesis inhibitors (peptidoglycan)
• -DNA replication inhibitors
• -RNA synthesis inhibitors
• -Protein synthesis inhibitors (30S and 50S)
• -Antimetabolites

Question 16

Cell wall active antibiotics

Answer 16

Disrupt peptidoglycan synthesis – ONLY effective against actively DIVIDING bacteria

Question 17

Membrane active antibiotics

Answer 17

Disrupt or interfere with membrane integrity/synthesis – effective against resting AND actively dividing bacteria

Question 18

Examples of cell wall synthesis inhibitors

Answer 18

• -β-lactams
• -Vancomycin (glycopeptides)
• -Bacitracin (polypeptides)

Question 19

β-lactams

Answer 19

Inhibit cell wall synthesis (ex. penicillins, cephalosporins, etc.)

Question 20

Mechanism of penicillin (and β-lactams in general)

Answer 20

Functions by blocking serine site in penicillin-binding protein (PBP) so that cross-linking cannot occur

Question 21

Resistance mechanisms of β-lactams

Answer 21

• -Altered/mutated transpeptidases (ex. PBP) that decrease affinity for antibiotic
• -Altered outer membrane permeability (ex. mutation in porins)
• -Presence of efflux pumps
• -Chemical modification of antibiotic (ex. β-lactamase)

Question 22

Vancomycin

Answer 22

Inhibits cell wall synthesis

Question 23

Mechanism of vancomycin

Answer 23

• -Recognizes and binds two D-ala residues on end of peptide chains
• -Binds to peptide chains and prevents them from interacting properly with transpeptidase

Question 24

Resistance mechanisms of vancomycin

Answer 24

Last D-ala residue is replaced by D-lactate so vancomycin cannot bind (cross-links successfully formed)

Question 25

Bacitracin

Answer 25

Inhibits cell wall synthesis by interfering with dephosphorylation in cycling of lipid carrier that transfers peptidoglycan subunits to the growing cell wall

Question 26

Protein synthesis inhibitors -- target and examples

Answer 26

- -Target bacterial ribosome (70S) | - -Includes tetracyclines, aminoglycosides, and macrolides

Question 27

Tetracyclines

Answer 27

Bacteriostatic that bind to 30S subunit and bind to it; broad spectrum

Question 28

Aminoglycosides

Answer 28

Bactericidal (generally) that bind to 30S subunit, oxygen-dependent and only effective against aerobic organisms

Question 29

Macrolides

Answer 29

Bacteriostatic that bind to 50S subunit; used as alternative to penicillin for those with allergies

Question 30

Examples of tetracyclines

Answer 30

Tetracycline, doxycycline

Question 31

Examples of aminoglycosides

Answer 31

Gentamicin, kanamycin

Question 32

Examples of macrolides

Answer 32

Erythromycin, azithromycin (Z-pack)

Question 33

Nucleic acid synthesis inhibitors examples

Answer 33

- -Quinolones - -Rifampin, rifabutin - -Metronidazole

Question 34

Quinolones

Answer 34

Bactericidal that inhibit DNA replication, recombination, and repair by affecting gyrase (topoisomerase)

Question 35

Rifampin and rifabutin

Answer 35

Bactericidal that bind to DNA-dependent RNA polymerase and inhibit initiation of RNA synthesis

Question 36

Metronidazole

Answer 36

Bactericidal that is reduced by bacteria to make toxic compounds that damage DNA

Question 37

Examples of antimetabolites

Answer 37

Sulfonamides and trimethoprim

Question 38

Antimetabolites

Answer 38

Target folate metabolism (since bacteria need to make it --> make DNA/RNA)