Beta-Lactams Flashcards
Beta-Lactams Resistance
B-lactamase catalyzes the hydrolysis B-Lactam
Beta-lactams MoA
inhibition of transpeptidase that “glue” the peptidoglycan strands together by cross linking
What do B-lactams mimic?
D-Ala-D-Ala (so transpeptidase binds to it)
Beta-Lactams Allergenicity
- 6-8% of pop
- cross reactivity between B-L’s
- B-L’s act as a hapten (inc antibodies = Ax rxn)
Penicillin G (Benzyl PCN)
- Beta-lactamase sensitive
- G+
- Parenteral
- Caution in Asthma
Penicillin V (Phenoxymethyl PCN)
- Beta-lactamase sensitive
- G+
- Oral
- more stable than PCN G in stomach b/c the electronegativity ether oxygen dec nucleophilicity of amide carbonyl
Methicillin
- Beta-lactamase Resistant
- Parenteral
- resistant due to steric hindrance
- not stable in stomach b/c of electron donation (more nucleophilic)
Nafcillin
- Beta-lactamase resistant
- parenteral
- more stable than methicillin in acid
Dicloxacillin, Oxacillin, Cloxacillin
- Beta-lactamase resistant
- Oral
- Isoxazoles
Ampicillin
- Beta-lactamase sensititve
- Broad spectrum
- oral
- Charged amino group = G- activity
Amoxicillin
- beta-lactamase sensitive
- broad sprectrum
- oral
- Charged amino group = G- activity
- better oral absorption than ampicillin
B-lactamase inhibitors MoA
acylate serine hydroxyl in B-lactamase -> B-lactamases can’t breakdown PCNs
Clauvanate, Sulbactam, Tazobactam, Avibactam
B-lactamase inhibitors
Piperacillin
- B-lactamase sensitive
- Broad spectrum
- Parenteral
- Added side chain looks like peptidoglycan = broader spectrum
Cephalosporin Allerginicity
- 3% of pop
- less common/severe than PCNs
Cephalexin
- 1st gen cepha
- oral
- G+
- unreactive CH3 on C-3 makes it more stable in stomach
Cefazolin
- 1st gen cepha
- parenteral
- G+
Cefuroxime
- 2nd gen cepha
- oral & parenteral
- G+ and some G-
- protect from light
- SYN oxime ether = resistant to B-lactamase
Ceftazidime
- 3rd gen cepha
- Parenteral
- more G- than G+
- oxime ether = resistant to B-lactamase
- Charged pyridinium ring increases aqueous solubility
Cefixime
- 3rd gen cepha
- Oral
- more G- than G+
- oxime ether = resistant to B-lactamase
- unreactive group at C-3 inc oral
Cefepime
- 4th gen cepha
- Parenteral
- G- and G+
- Syn methoximine stabilizes against B-lactamase
- N-methylpyrrolidine is good leaving group, inc parenterally active
Ceftaroline
- 5th gen cepha
- parenteral
- Ceftaroline fosamil (prodrug)
- broad spectrum
- resistant to B-lactamase
- charged N, inc G- activity
Imipenem
- Carbapenems
- Parenteral
- broad spectrum
- N-formiminoyl derivative of thienamycin (thiena is too reactive to use)
- Sulfar atom in PCN is replaced by methylene
- inhibits B-lactamase
- hydrolyzed by dehydropeptidase-1
- Combo w/ CILASTATIN to inhibit D-1
Aztreonam
- Monobactam
- Parenteral
- sulfamic acid makes it active/reacts with PBPs
- oxime ether = resistant to B-lactamse
- G- for severe infections
- No cross Ax w/ PCNs and Cepha (except Ceftazidime)
Vancomycin
- Glycopeptide
- MoA: inhibitor of G+ cell wall biosynthesis
- G+ only
- Resistance: mut of peptidoglycan cell wall precursor
- Tx: MRSA
AE: Red skin rash, nephrotoxic, ototoxic
Oritavancin, Telavancin, Dalbavancin
- Lipoglycopeptides
- MoA: inhibits transpeptidase and transglycosylation
- Broad spectrum
- Dalba and Orita LONG t1/2, single dose
Synercid
- 30% Quinupriston, 70% Dalfopriston
- static alone, cidal together agsinst MRSA