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36 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What is the structure of penicillin important for activity?
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beta-lactam ring
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What does penicillin bind to on a microbe?
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penicillin-binding proteins PBPs)
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What is the primary target for beta-lactam drugs?
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transpeptidases (a PBP) for peptidoglycan synthesis
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What drugs are transpeptidases inhibited by?
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- penicillins
- cephalosporins - carbapenems |
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Describe how penicillin leads to cell suicide
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-penicillin binds to active serine on transpeptidase
-enzyme can't dissociate -cell wall synthesis inhibited - call lyses |
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Is penicillin bactericidal or bacteristatic?
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CIDAL!
- since the bacterial cell wall will not cross link, cell lysis |
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What is the main cause of bacterial resistance to penicillins?
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- beta-lactamase (produced by bacteria) cleave the beta-lactam ring in penicillin
- enzymatic destruction of penicillin |
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How have beta-lactamases evolved?
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-single amino acid subs
- very quickly! |
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How can you avoid destruction of penicillin by a penicillinase (beta-lactamase)?
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- use a b-lactamase resistant penicillin
- use a b-lactamase inhibitor + penicillin |
nothing is really completely resistant to beta-lactamase.... the bugs will catch up
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Methicillin
Nafcilin Oxacillin |
beta-lactamase-resistant penicillins
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Clavulanic acid
Sulbactam Tazobactam |
-beta-lactamase inhibitors
-no therapeutic activity alone but prevent the destruction of penicillin when combined -potentiation reaction |
clavulanic acid binds to beta-lactamase and won't release the enzyme
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Alterations in PBPs lead to...
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decreased affinity for penicillins
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strep pneumoniae expresses what kind of resistance?
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- chromosomally-mediated changes of PBPs
- resistance to several b-lactams - changes to already existing PBPs - to get high level resistance need changes to multiple PBPs |
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How did methicillin-resistant staph aureus (MRSA) aquire resistance?
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- resistant thru expression of NEW PBP
- low affinity for penicillins b/c of the PBP2a (mecA) |
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PBP2a is from what gene?
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mecA
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PBP2a
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- encoded by mecA
- transpeptidase - low affinity for b-lactams - can still crosslink in presence of penicillin = rigid cell wall - novel PBP - found in MRSA |
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Community-associated MRSA
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- resistant to b-lactams
- sensitive to clindamycin, trimethoprim / sulfamethoxazole |
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Hospital-aquired MRSA
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- very difficult to treat
- high level of resistance to b-lactams - tx with vancomycin |
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What are the two major mechanisms for resistance to penicillin?
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- b-lactamase
- PBP alterations (PBP2a) |
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Absorption of penicillin
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variable, depends on side chain (can be oral)
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Distribution of penicillin
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- widely distributed
- does NOT penetrate CSF well (will increase when meninges inflamed) |
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Metabolism of penicillin
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- some in liver
- t1/2 = 30-60 min |
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Excretion of penicillin
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- golmerular filtration
- mostly unchanged in urine - some hepatically excreted |
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narrow spectrum penicillins
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active against gram positive bacteria
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extended spectrum penicillins
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gram positive and some gram negative
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How can you extend the spectrum of activity of b-lactamase sensitive penicililns?
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combine with b-lactamase inhibitor
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Penicillin G
Penicillin V |
- narrow spectrum (gram +)
- beta-lactamase SENSITIVE Tx: streptococcal infections |
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Methicillin, nafcillin
oxacillin, cloxacillin dicolxacililn |
- narrow spectrum (gram +)
- beta-lactamase RESISTANT Tx: staph aureus infections |
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Ampicillin, amoxicillin
Ticarcillin, mezlocillin, piperacillin |
- extended spectrum
- beta-lactamase SENSITIVE - Tx: e. coli or pseudomonas aeruginosa (only second row) |
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benzathine penicillin G
procaine penicilin G |
delayed absorption penicillins
Benzathine is once monthly |
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What are the clinical uses for delayed absorption penicillins?
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- streptococcal pharyngitis
- syphilis (slow release of drug to bloodstream) |
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Augmentin
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amoxicillin + clavulanic acid
Tx: otitis media, sinusitis, S. aureus |
penicillin + b-lactamase inhibitor
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Timentin
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ticarcillin + clavulanic acid
Tx: s. aureus, bacteroides |
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Unasyn
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ampicillin + sulbactam
Tx: s.aureus, e. coli |
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Zosyn
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piperacillin + tazobactam
Tx: complicated skin infections, intraabdominal infections |
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Adverse rxns to penicillins
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- diarrhea after oral dose
- superinfections - seizures (seizure pron pts or renal dysfunction pts) - hypersensitivity - anaphylaxis |
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