Antibiotics II

Question 1

vancomycin - overview

Answer 1

*complex GLYCOPEPTIDE (large)
*interferes with cell wall synthesis (not in the same way as beta lactams)
*bactericidal (less rapidly than anti-staph penicillins)

Question 2

vancomycin - mechanism of action

Answer 2

*binds to d-alanine-d-alanine of peptide precursor
*inhibits peptidoglycan synthesis via steric hinderance

Question 3

vancomycin - mechanism of resistance

Answer 3

change from d-alanine-d-alanine to d-alanine-d-lactate

Question 4

vancomycin - spectrum

Answer 4

gram positive organisms (including MRSA)

Question 5

vancomycin - important pharmacokinetic property

Answer 5

*if given orally, it does NOT get into the bloodstream
*if given IV, does not get into GI tract

Question 6

main drug for C diff ?

Answer 6

ORAL vancomycin

Question 7

dalbavancin

Answer 7

*complex lipoglycopeptide
*same mechanism of action as vancomycin
*LONG HALF LIFE (useful in infections of IV drug users)
*active against gram-positive bacteria

Question 8

antibiotic classes that inhibit the ribosome

Answer 8

macrolides, aminoglycosides, clindamycin, tetracyclines

Question 9

macrolides - mechanism of action

Answer 9

inhibits protein synthesis by binding to ribosome

Question 10

macrolides - mechanism of resistance

Answer 10

1. *ribosomal methylation (prevents macrolide binding)
2. drug efflux (using protein channels to pump antibiotic out of cell)

Question 11

examples of macrolides

Answer 11

1. erythromycin - use for pathogens without cell walls and gram positives; gives really bad diarrhea (we don’t use anymore)
2. azithromycin - better than erythro; common for respiratory tract infections

Question 12

aminoglycosides - mechanism of action

Answer 12

inhibit protein synthesis by binding to ribosome

Question 13

pharmacodynamics for aminoglycosides

Answer 13

concentration-dependent killing: Cmax / MIC ( > 5)

Question 14

examples of aminoglycosides

Answer 14

-gentamicin
-tobramycin
-streptomycin
-amikacin

Question 15

aminoglycosides - spectrum of activity

Answer 15

*gram negative aerobes
*synergistic with beta lactams!

Question 16

aminoglycosides - mechanism of resistance

Answer 16

enzymatic inactivation of the drug itself (sulfation, acetylation, or phosphorylation)

Question 17

downsides of aminoglycosides

Answer 17

*low therapeutic index (may be toxic)
*need to monitor serum levels to limit toxicity (deafness, renal failure)

Question 18

clindamycin - mechanism of action

Answer 18

inhibits protein synthesis by binding to ribosome

Question 19

clindamycin - mechanism of resistance

Answer 19

*ribosomal methylation

Question 20

clindamycin - spectrum and uses

Answer 20

*gram positive cocci (staph and strep)
**used for Group A Strep (SHUTS DOWN TOXIN PRODUCTION for necrotizing fasciitis)
*above the diaphragm anaerobes

Question 21

tetracyclines - mechanism of action

Answer 21

inhibits protein synthesis by binding to ribosome

Question 22

tetracyclines - mechanism of resistance

Answer 22

drug efflux

Question 23

tetracyclines (especially doxycycline) - spectrum and uses

Answer 23

*gram positive, some gram negative
*MYCOPLASMA, CHLAMYDIA, RICKETTSIA, malaria
*go-to for tick-borne infections

Question 24

TMP/SXT (bactram) - mechanisms of action

Answer 24

*blocks 2 consecutive steps in the biosynthesis of nucleic acids
1. PABA to folic acid
2. folic acid to folinic acid

Question 25

TMP/SXT - mechanism of resistance

Answer 25

increased production of dihydrofolate reductase (bacteria just makes a LOT more to overcome antibiotic)

Question 26

TMP/SXT - spectrum

Answer 26

broad spectrum, including MRSA *used for pneumocystis jirovecii

Question 27

metronidazole

Answer 27

DNA strand breaking effect *used for anaerobes BELOW the diaphragm

Question 28

fluroquinolones - mechanism of action

Answer 28

*inhibit DNA gyrase and topoisomerase (stops DNA replication)

Question 29

fluroquinolones - mechanism of resistance

Answer 29

1. mutation of DNA gyrase/topoisomerase 2. drug efflux

Question 30

pharmacodynamics of fluroquinolones

Answer 30

AUC/MIC > 35

Question 31

examples of fluroquinolones

Answer 31

-levofloxacin -moxifloxacin -ciprofloxacin

Question 32

fluroquinolones - spectrum of activity

Answer 32

*ALL have good gram NEGATIVE activity (cipro best against pseudomonas) *ALL cover the "atypicals" (mycoplasma, chlamydia, legionella *covers TB

Question 33

what drugs can be used for traveler's diarrhea

Answer 33

azithromycin or ciprofloxacin

Question 34

rifampin - mechanism of action

Answer 34

inhibits DNA-dependent RNA polymerase *penetrates biofilms well

Question 35

rifampin - mechanism of resistance

Answer 35

mutations in the DNA-dependent RNA polymerase

Question 36

something to note about rifampin

Answer 36

body fluids turn ORANGE (tears, urine)

Question 37

daptomycin - mechanism of action

Answer 37

calcium-dependent increase in membrane permeability to potassium *a LIPOPEPTIDE

Question 38

daptomycin - spectrum

Answer 38

all gram positives, including MRSA

Question 39

linezolid - mechanism of action

Answer 39

inhibits protein synthesis at the level of ribosomal translation *can be used for MRSA

Question 40

polymxin B - mechanism of action

Answer 40

intercalates with LPS in gram negative membrane *we don't use it anymore (toxic)

Question 41

fidaxomicin

Answer 41

*nonabsorbable oral drug *useful for C diff *VERY expensive (we should use vancomycin) *example of a macrolide