Antibiotics II Flashcards
vancomycin - overview
*complex GLYCOPEPTIDE (large)
*interferes with cell wall synthesis (not in the same way as beta lactams): binds to D-Ala-D-Ala portion of cell wall precursors to inhibit cell wall peptidoglycan formation
*bactericidal (less rapidly than anti-staph penicillins)
vancomycin - mechanism of action
*binds to d-alanine-d-alanine of peptide precursor
*inhibits peptidoglycan synthesis via steric hinderance
vancomycin - mechanism of resistance
change from d-alanine-d-alanine to d-alanine-d-lactate
vancomycin - spectrum
gram POSITIVE organisms (including MRSA & C diff)
vancomycin - important pharmacokinetic property
*if given orally, it does NOT get into the bloodstream (good for C diff)
*if given IV, does not get into GI tract (bad for C diff)
main drug for C diff ?
ORAL vancomycin
dalbavancin
*complex lipoglycopeptide
*same mechanism of action as vancomycin
*LONG HALF LIFE (useful in infections of IV drug users)
*active against gram-positive bacteria
antibiotic classes that inhibit the ribosome
- macrolides (50S subunit - azithromycin, erythromycin, clarithromycin)
- aminoglycosides (30S subunit - gentamicin, neomycin, amikacin, tobramycin, streptomycin)
- clindamycin
- tetracyclines (30S subunit - tetracycline, doxycycline, minocycline)
macrolides - mechanism of action
*inhibits protein synthesis by blocking translocation; bind to 50S ribosomal subunit
*examples: azithromycin, erythromycin, clarithromycin
macrolides - mechanism of resistance
*ribosomal methylation of 23S rRNA-binding site (prevents macrolide binding)
*examples of macrolides: azithromycin, erythromycin, clarithromycin
examples of macrolides
- erythromycin - use for pathogens without cell walls and gram positives; gives really bad diarrhea (we don’t use anymore)
- azithromycin - better than erythro; common for respiratory tract infections
- clarithromycin
aminoglycosides - mechanism of action
*inhibit protein synthesis by binding to 30S subunit of ribosome
*examples: gentamicin, neomycin, amikacin, tobramycin, streptomycin
pharmacodynamics for aminoglycosides
concentration-dependent killing: Cmax / MIC ( > 5)
examples of aminoglycosides
-gentamicin
-tobramycin
-streptomycin
-amikacin
aminoglycosides - spectrum of activity
*gram negative aerobes
*synergistic with beta lactams!
aminoglycosides - mechanism of resistance
enzymatic inactivation of the drug itself (sulfation, acetylation, or phosphorylation)
downsides of aminoglycosides
*low therapeutic index (may be toxic)
*need to monitor serum levels to limit toxicity (deafness, renal failure)
clindamycin - mechanism of action
inhibits protein synthesis by binding to 50S subunit of ribosome
clindamycin - mechanism of resistance
*ribosomal methylation
clindamycin - spectrum and uses
*gram positive cocci (staph and strep)
**used for Group A Strep (SHUTS DOWN TOXIN PRODUCTION for necrotizing fasciitis)
*above the diaphragm anaerobes
tetracyclines - mechanism of action
*inhibits protein synthesis by binding to 30S subunit of ribosome
*examples: tetracycline, doxycycline, minocyline
tetracyclines - mechanism of resistance
drug efflux
tetracyclines (especially doxycycline) - spectrum and uses
*gram positive, some gram negative
*MYCOPLASMA, CHLAMYDIA, RICKETTSIA, malaria
*go-to for tick-borne infections
TMP-SMX (trimethoprim-sulfamethoxazole / bactram) - mechanisms of action
*blocks 2 consecutive steps in FOLATE synthesis, thus blocking biosynthesis of nucleic acids
1. bacterial dihydrofolate reductase (PABA to folic acid)
2. dihydropteroate synthase (folic acid to folinic acid(
TMP/SXT - mechanism of resistance
increased production of dihydrofolate reductase (bacteria just makes a LOT more to overcome antibiotic)
TMP/SXT - spectrum
broad spectrum, including MRSA
*used for pneumocystis jirovecii
metronidazole
*forms toxic free radical metabolites in the bacterial cell that damage DNA
*used for anaerobes BELOW the diaphragm
fluroquinolones - mechanism of action
*inhibits DNA gyrase / topoisomerase II (stops DNA replication)
*examples: “-floxacins”: ciprofloxacin, ofloxacin, levoflaxacin, moxifloxacin
fluroquinolones - mechanism of resistance
- mutation of DNA gyrase/topoisomerase
- drug efflux
pharmacodynamics of fluroquinolones
AUC/MIC > 35
examples of fluroquinolones
-levofloxacin
-moxifloxacin
-ciprofloxacin
fluroquinolones - spectrum of activity
*ALL have good gram NEGATIVE activity (cipro best against pseudomonas)
*ALL cover the “atypicals” (mycoplasma, chlamydia, legionella
*covers TB
what drugs can be used for traveler’s diarrhea
azithromycin or ciprofloxacin
rifampin - mechanism of action
inhibits DNA-dependent RNA polymerase
*penetrates biofilms well
rifampin - mechanism of resistance
mutations in the DNA-dependent RNA polymerase
something to note about rifampin
body fluids turn ORANGE (tears, urine)
daptomycin - mechanism of action
*a LIPOPEPTIDE that disrupts cell membranes of gram positive cocci by creating transmembrane channels
*calcium-dependent increase in membrane permeability to potassium
daptomycin - spectrum
all gram positives, including MRSA
linezolid - mechanism of action
*inhibits protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit and preventing formation of the initiation complex
*can be used for MRSA
polymxin B - mechanism of action
intercalates with LPS in gram negative membrane
*we don’t use it anymore (toxic)
fidaxomicin
*nonabsorbable oral drug
*useful for C diff
*VERY expensive (we should use vancomycin)
*example of a macrolide
