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RavLect11: PCNs

Penicillins

TermDefinition
Action of Penicillins Bactericidal Beta-lactam: requires peptidoglycan and PBP to work Cell wall active: must bind PBP to interrupt cellular structure & inhibit cell wall synthesis Synergistic with aminoglycosides, additive w/ quinolones
Mechanims of penicillin resistance Beta-lactamase/Penicillinase Altered cell wall penetration PBP’s PBP affinity alteration
Penicillinase (enzyme alteration) Resistance from PCNs
PBP affinity alteration (mutation of proteins and binding affinity) B-lactamase inhibitors will NOT work PBP2x for strep pneumonia PBP2a for staph aureus
Natural Penicillins Pen G Pen G potassium or sodium Pen VK Pen G Benzathine Pen G Procaine Combination of Benz and Procaine
Activity of Natural PCNs Neisseria (resistance building) - Pen G good for N. meningitidis Strept pneumo (not good for PBP2x); Pen G benzathine for S. pharyngitis & syphilis Also commonly used for dental infection prophylaxis
Excretion of PCNs Rapid excretion in urine (blocked with Probenecid. This raises PCN levels) But no dose adjustment needed in renal dysfunction. Warning: extra high PCN dose in pt with renal dysfxn could lead to seizures!
Tissue penetration of PCNs PCNs penetrate most tissues except the prostate, the eye and the CSF unless inflammation exists
Are PCNs concentration or time dependent? Beta-lactams are concentration INdepedent (TIME above MIC is more important than concentration level). Thus, doubling the dose is not as effective as a long-acting or continuous infusion.
Pen G Usually in IV form, but available in IM Contain Na+ and K+, so problematic in ptx with HF & renal dysfxn.
Pen V Oral form. QID b/c very short half life! Take on empty stomach since acid deteriorates beta-lactam ring.
Pen G Benzathine IM weekly Pen G Procaine for Strep pharyngitis and Syphilis
Penicillinase Resistant PCNs (additional acyl side chain prevents B-lactamase ring destruction by penicillinases) Methi-, Naf-, Oxa-, Cloxa-, Dicloxa- cillins (mainly use Naficillin IV & Dicloxacillin PO)
Penicillinase Resistant PCN spectrum of action for Staphylococcal (MSSA, MSSE) skin, bone infection (only used after sensitivity has been proven. Not used empirically) NOT active if methicillin resistant (MR-) NOT active against Enterococcus, Listeria
Ampicillin dose adjustment? adjust Ampicillin for renal dysfunction
Penicillinase Resistant PCN dose adjustment? No renal or hepatic adjustment needed (but Naf requires hepatic monitoring since it elevates AST and causes hepatotoxicity)
Naficillin 1) Staph sensitive 2) IV form 3) thrombophlebitis 4) monitor liver function
Methicillin only used for testing for MRSA or MRSE since it is renally toxic
Aminopenicillins Ampicillin (IV) take on empty stomach Amoxicillin (PO) take with or w/o food. Amoxil is TID b/c short half life
Most common causes of CAP, RT (resp tract) infections, otitis media, meningitis Strept pneumoniae H. influenza.
Aminopenicillin spectrum of action Enterococcus especially! usually combined: [Amp + Gent] Strept pneumoniae (resistance building) H. influenza. Listeria Monocytogenes E. Coli Klebsiella
Carboxypenicillin Ticarcillin
Ticarcillin SoA No G+ activity More active against G- organisms (Enterobacteriaceae, Pseudomonas aeruginosa -but not as effective as Piperacillin) Not v. effective against Klebsiella
Ticarcillin ADRs Renal dysfunction accumulation Na+ overload platelet dysfunction (binds ADP like Plavix so it has antiplatelet properties) MUST monitor platelets! hypokalemia
Ureidopenicillins Piperacillin
Piperacillin SoA Amp SoA + #1 ABx for Pseudomonas (think "P"). If a drug can Tx Pseudomonas, it can Tx all G- (except ESBL & NDM1)! SPACE organisms (G-): Serratia Pseudomonas Acinetobacter Citrobacter Enterobactericeae family
Unasyn Ampicillin + Sulbactam
Augmentin Amoxicillin + Clavulanic acid
Timentin Ticarcillin + Clavulanic acid
Zosyn Piperacillin + Tazobactam
β-lactamase inhibitors Bactams & clavulanic acid (additives to the baseline drugs of "godzilla-cillins")
Godzilla-cillins SoA B-lactamase producing- E.coli B-lactamase producing- B. fragilis (anaerobe) & whatever the baseline drugs cover NOT effective for ESBL producers
Clavulanic acid ADRs diarrhea & liver dysfxn so DON'T give too much by doubling dose of Godzilla-cillins!
Augmentin (Amox + Clav. acid) ADRs Diarrhea Yeast infection
Why use unasyn over ampicillin for intra-abdominal infection? E. coli and b. frag (anaerobe) produce beta lactamase. FYI: Enterococcus does NOT produce B-lactamase.
Penicillin ADRs ALLERGIC RXNS! hemolytic anemia (rare) drug-related fever Diarrhea Neutropenia from prolonged use Electrolyte disturbances Seizures at high doses Inactivated when mixed with AGs Timentin has platelet dysfxn
Pediatric dose of Amoxicillin 80-100mg/kg/day
Created by: cheeoh
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