Antibiotics III Flashcards
3 Steps of Peptidoglycan/Cell Wall Synthesis
- Monomer biosynth/transport from cyt to periplasm
- Monomer polymerization/transglycosidase
- Polymer cross-linking/transpeptidation
6 3rd Phase/Transpeptidation Inhibitors
Penicilliins Methicillin Ampicillin Cephalosporins Carbapenems Monobactams
1 2nd Phase/Transglycosidase Inhibitor
Vancomycin
3 1st Phase Inhibitor (1st 2 biosynth 2nd transport)
Fosfomycin
Cycloserine
Bacitracin
2 Inhibitors of Beta Lactamases
Clavulanic Acid
Sulbactam
3 Aspects about Cell Wall Synth Inhibitors
Bactericidal
Require bacterial growth to be effective
Mechanism of death is autolysis (imbalance bw cell wall synth and degradation)
2 Factors that Determine Spectrum
Hydrophilicity (ability to penetrate outer membrane and cell wall, more better)
Ability to Bind Specific Transpeptidases (bac have different ones)
Mech of Beta Lactam Inactivation of Transpeptidases
Suicide substrate inhibition: covalent bond to enzyme
Most Common Side Effect w/ Beta Lactams
Hypersensitivity from rxn to serum prots. If have to one beta lactam, don’t use others
Most Common Resistance(s) to Beta Lactams
Plasmid-borne beta-lactamase (although intrinsic transpeptidase muts do occur)
Penicillin G vs. V
G is acid labile, injected, while V is acid stable, oral
Methicillin (2)
Beta-lactam refractor to beta-lactamase hydrolysis bc of steric hindrance of protective side chains
Only works for S. aureus
Ampicillin
Broad spectrum penicillin bc has charged amino group that allows it to pass through membranes of G-
Solution to Lack of Broad Spectrum Beta-Lactamase Refractory Penicillin
Combine broad spectrum penicillin w/ Beta-lactamase inhibitor
MRSA
Methicillin resistant, still can’t hydrolyze but other intrinsic mechs on transposon easily transmitted w/ other resistance genes. Resistance often variable
Cephalosporins (2)
R side chain makes them less of target for Beta-lactamases
Developed progressively to wider spectrum including G-s
Carbepenems
Broad spectrum but not MRSA< C. dificile, or Legionella
Monobactam (2)
Aztreonam active against G- but not G+. Nasty side effects
Vancomycin (2m, ra, t, re, sf)
m - Inhibits peptidoglycan synth in 2 ways: inhibits NAM/NAG polymer synth & inhibits cross linking
ra - G+/MRSA
t - red man syndrome
re - VanA depsipentapeptide where crosslink chain is Lactate instead of Ala
sf - antibiotic of last resort
Fosfomycin
Broad-spectrum MurA inhibitor effective on G- UTI
Cycloserine
D-Ala analogue used against M. tuberculosis
Bacitracin
Bactoprenol inhibitor used topically
Daptomycin
Lipopeptide useful for G+/VRSA via cytoplasmic membrane depolarization
