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Winter_Antibiotics - Goodfor Notgoodfor Notesaboutuse...

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Inhibitors of Cell Wall Synthesis Good for Not good for Notes about use Beta Lactams: Penicillins Block cell wall synthesis Covalently attach to penicillin binding proteins (PBPs) Mimic D ala D ala substrate Gram + s generally susceptible Bactericidal if autolysins present, if cells are growing, and if have osmotic pressure Not bactericidal in endocarditis, chronic osteomyelitis, or if dormant; Enterococus downregulates autolysins E. coli transpeptidase (PBP 1a and 1b) permanently inactivated by beta lactam cell wall can’t be crosslinked and stabilized bacterium lyses (facilitated by autolysins) Block PBP2 cell is round instead of rod shaped Block PBP3 can’t form septum, so get huge filamentous cells Equal lethality for all 3 targets Short half life Renal excretion (unchanged) Probenecid blocks tubular secretion longer half life IM forms absorbed more slowly, but combine w/ local anesthetic b/c painful Beta lactam ring broken by bacterial beta lactamases Cross allergenic Don’t cross BBB or get to prostate or eye Minimal post antibiotic effect Generally non toxic Allergy: rash, interstitial nephritis Marrow arrest neutropenia Coat platelets ื ± bleeding time High levels in CSF seizures 1 st generation penicillins PCN G PCN V Naturally occurring Susceptible Gram + organisms o e.g. group A Strep, Treponema pallidum (syphilis) o Unlike 2 nd gen PCNs , active against Enterococcus and Listeria Not active against Gram – bacteria S. aureus can acquire penicillinase on plasmid (pretty much all Staph have this, so 1 st gen not useful) S. pneumoniae can get new PBP via transformation Drug of choice for prevention and tx of GAS (strep throat) For prevention and tx of syphilis For tx of viridans streptococcal endocarditis (but other drugs work for this as well) 2 nd generation penicillins Methicillin nafcillin dicloxacillin oxacillin (mnemonic: I met a na sty ox that is resistant to penicillinase) Resistant to penicillinase of MSSA Active against methicillin sensitive S. aureus ( MSSA ) Still active against other Gram + bacteria such as hemolytic Strep None are active against MRSA o MRSA has new mec gene from transduction novel PBP has low affinity for all beta lactams Not active against Gram – organisms Not active against Enterococci (Gram + cocci) Not active against Listeria (Gram + rod) Less active than 1 st gen PCNs against Gram +s that don’t make beta lactamase Methicillin can cause allergic interstitial nephritis Nafcillin and oxacillin can cause hepatitis b/c hepatically excreted (in addition to renal) For tx of MSSA Can be used for Strep, but not drugs of choice 3 rd generation penicillins (aminopenicillins) Amoxicillin ampicillin Made to treat some Gram – organisms that don’t make beta lactamases Oral or IV
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