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IOS 10 Antibiotics

B-lactam, Fluoroquinolone, Vancomycin, Synercid, Linezolid,

QuestionAnswer
Aminoglycosides MOA Passive diffusion, active transport(O2 required).Binds selectively to 30S or 50S ribosomal subunit. Intefere with protein synthesis-Block initation of tRNA, translation of mRNA. Possible increase in permibility due to gene alterations.
Aminoglycosides spectrum of activity ONLY aerobes mainly Gram - P aeruginosa, Acinobacter
Aminoglycoside resistance Plasmid mediated via modifying enzymes
Aminoglycoside enzyme resistance rank Amikacin> Tobra> genta
Kanamycin Used as a surgical irritant
Streptomycin TB treatment
Alteration of B-Lactam nucleus causes B-lactam inactivity
Side chain of B-lactam Increase stability, decrease excretion
Extended spectrum Pen's Penicillinase resistant, carboxypenicillins, Ureidopenicillins
B-lactam MOA PBP irreversible inhibition (transpeptidase) decrease cell synthesis and remodeling
PBP acts to Catalyze the transpeptidase rxn
Natural penicillins ADME Poor, extracellular no CNS, renal
Natural spectrum of activity Gram + aerobes Gram - Only Neissera, Not B. fragelis (syphillis)
Penicilline resistant ADME varies, nafcillin (IV)& hepatic
Penicilline spectrum of activity Gram + Staph Aureus, No enterococci
Aminopenicillins ADME Good, good, renal
Aminopenicillins spectrum of activity Created for gram - -excellent on lactose, H.influenza
Carboxypenicillins spectrum of activity GRAM + Staph aureus, Strep Gram - Enteric bacilli, P. aeruginosa, H. inf
Ureidopenicillins spectrum of activity Great Gram + S. Auresu & Great Gram - lactose, P.aeruginosa, H. influenza
Penicillins SE GI, Rash (amoxicillin), Hematologic, CNS, electrolyte, increased LFT's
PEN cross HYPERsen 7-10% cephalosporins, carbapenems, rare Monobactams-aztreonam
Carbapenems hypersensitivity 100% with cephalosporins
PEN monitoring C. difficile, superinfection
PEN DI mixing with aminoglycosides, probenecid inhibits secretion
B-lactamase and penicillinase inhibitors work in anaerobic organisms, and Gram - aerobic bacilli
1st generation cephalosporin cefazolin, cephalexin
2nd generation cephalosporings cefaclor, cefuroximine,cefoxitin
3rd generation cephalosporins cefpodoxime, ceftrixone, ceftazidine
4th generation cephalosporin cefepime
Cephalosporins ADME good, well dist, renal
cephalosporins have weak activity on anerobics (except cefoxitin)
1st generation spectrum of activity Great gram + stable against B-lactams and penicilliniase
2nd generation spectrum of activity gram + ok, gram - lactose, H. influenza, moraxella
3rd generation spectrum of activity Great Gram - (lactose, H.I, mora) but inactivation by enzymes (ceftazidine)-P. aeruginosa)
Ceftriaxone SE hepatic sludging in neonates
4th generation spectrum of activity Awesome on Gram - P. aeruginosa, Gram + good similar to 1st generation
4th generation ADME best CNS penetration of cephalosporins
cephalosporins hypersen 1-3% occurance
Carbapenems Imipenenems, Ertapenem
Carbapenem spectrum of activity Gram - is AWESOME, enterobact, H.Inf, Mora, neisser, P. aeru, acinob. Anaerobic AWESOme
Carbapenenem resistance similar to B-lactams but less B-lactamase resistance, and loss of porins
Probenecid causes inhibition of tubular secretion Penicillins, cephalosporins, carbapenenems
Monobactams Azetreonam
Azetronam spectrum of activity Gram - P. aeruginosa
Fluroroquinolones MOA Topo II DNA gyrase(gram-) Topo IV (C,E) Gram + inhibited
TOPO II (DNA gyrase) inhibition Gram -bind part A, B site of ATP hydrolysis and DNA movement
TOPO IV (C, E) inhibition Prevents daughter chromasomes from segregating.
Fluoroquinolone resistance TOPO II (DNA gyrase mutation) or TOPO IV, efflux proteins 2 mutations needed
Fluoroquinolone ADME excellent, extensive, renal (moxi- hepatic)
Ciprofloxacin activity Gram - Awesome P.aeruginosa, Atypicals wow! (BID dosing)
ceftriaxone t1/2 is 8hrs and QD dosing
Fluoroquinolone dosing is QD (Cip-BID) (Moxi-13 hr)
Fluoroquinolones are not active against MRSA and enterococci
Fluoroquinolone spectrum of activity Gram - excellent, Gram+ good, anaerobic, Atypicals
Fluoroquinolone DI Antiacids, milk products, divalent cations, ferrous sulfates, p450s, theophylline, warfarin
Vancomycin spectrum of activity ONLY Gram + MRSA S. epidermis, coagulase negative staph, strep, enterococci (with PEN, AMP), Anaerobic, C. DIFF
treats C. Diff vancomycin
Vancomycin MOA High affinity binding for D-alanyl-D-alanine to block release and prevent cross linking
Slow bacterialcidal vancomycin
Vancomycin resistance Change of D-alanyl-D-alanine to D-alanyl-D-lactate and plasmid mediated MOA to interfere with transport into bacteria
Vancomycin ADME poor absorption, limited CNS, renal BID dosing
Vancomycin SE Nephrotoxic, ototoxic, Phlebis
Vancomycin DI Concommitantly with aminoglycosides
Streptogramins- Synercid- Quinupristin/dalfopristin
Synercid spectrum of activity Gram + MRSA and others , some atypicals
Streptogramins MOA Bind 50s ribosome to prevent elongation
Streptogramins resistance Plasmid mediated modification to binding 50s ribosome
Oxazolidinones Linezolid
Bacteriostatic either dalfopristin or quinupristin alone or linezolid
Linezolid spectrum of activity Gram + stapyh, strep, MSRA, S.epider, caogulas neg, E. faecalis and vancomycin resistant enterococci
Linezolid MOA Prevents the formation of tRNAm mRNA of 70s to block formation of the initiation comples (does not block elongation or termination)
Linezolid DI Competitive inhibitor of MAOA and MAOB, and serotoin syndrome reported.
Synercid MOA Binds 50s ribosome to prevent elongation
Cyclic Lipopeptide Daptomycin
Daptomycin MOA Rapid depolarization of cell membrane and efflux of potassium
Daptomycin ADME ok, low in respiratory due to surfactant inactivation
Daptomycin SE GI, HA, elevation of creatine phosphokinase (watch statins)
PD study of the relationship between concentration of drug and the response obtained by a patient
PK ADME useful for the prediction of serum concentration, CL, T1/2
Concentration dependant antibiotics Fluoroquinolones, Aminoglycsides, Metronidazole, Ketolides
Time dependant B-lactams, cephalosporins, monobactams, carbapenems, vancomycin, azithromycin, macrolides, clindamycin
Concentration dependant define Comparision of concentation vs MIC studies as we increase concentration we increase bactericidal activity
Time dependant antimicrobials From Concentration and MIC studies we see killing activity is only marginally increased if concentration is increased above MIC, the PD relationship for these drugs is duration that con exceeds MIC.
Time dependant goals Time> MIC 50% or more
Fluoroquinolone Concentration dependant goals Cmax/MIC >10-12 correlates with favorable clinical and microbiological response
Fluoroquinolone concentration goals AUC/MIC Gram - 125-250
Fluoroquinolone concentration goals AUC/MIC Gram+ > 30
Aminoglycoside ring structures Aminocyclitol and 2-deoxystreptamine
No cephalosporin has spectrum of acitivy against MRSA, entercocci, listeria, or atypicals
Created by: liza001