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30 Cards in this Set
- Front
- Back
All beta-lactam antibiotics inhibit bacterial growth by interfering with the _______ reaction of bacterial cell wall synthesis
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transpeptidation
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_______ is probably acylated by penicillin (conformation of penicillin is very similar to that of D-alanyl-alanine)
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transpeptidase
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homologous recombination between PBP genes of different bacterial species
Acquisition of additional PBP via transposons (methicillin-resistant S. aureus) |
acquired resistance
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Impaired penetration of drug to target PBP
Occurs only in Gram(-) because of their impermeable outer cell wall membrane antibiotics cross outer membrane and enter cell via outer membrane protein channels (porins). Down-regulation of porins can impair antibiotic entry (Pseudomonas aeruginosa is resistant to most antibiotics since it lacks porins) Gram (-) organisms may also produce efflux pumps (transport the antibiotic from the periplasm back across the membrane) |
mechanism of penicillin resistance
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Class__ (extended spectrum β-lactamase): degrade penicillin, some cephalosporins and some carbapenems
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A
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Class___(Zn-dependent): destroy all β-lactams except aztreonam
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B
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Class ___ beta lactamase: cephalosporins
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C
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Class___ beta lactamase: cloxacillin
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D
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Class__and __ beta lactamase can be inhibited by clavulanate
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A and D
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Gram (), β lactamase:
Secreted extracellularly in large amounts Most are penicillinases Encoded by plasmids |
+
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Gram (), β lactamase is located in the periplasmic space, small amounts.
Encoded by plasmids and chromosome Can hydrolyze both penicillins and cephalosporins |
-
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works against Gram (+) cocci, sensitive to pencillinase
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natural penicillins V and G
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Less potent than natural penicillin, used in S. aureus
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Penicillinase-resistant penicillins
Methicillin (discontinued), nafcillin, oxacillin, cloxacillin, dicloxacillin |
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Extended spectrum penicillins that works against Haemophillus influenzae, E. coli, Proteus mirabilis
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Aminopencillins
Aminocyllin, amoxycillin |
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Extended spectrum penicillins that works against Pseudomonas, Enterobacter, Proteus spp.
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Carboxypenicillins
Carbenicillin (discontinued), ticarcillin |
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Extended spectrum penicillins that works against Pseudomonas, Klebsiella
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Ureidopencillins
Mezlocillin (discontinued), piperacillin |
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Low acid stability. Degraded by gastric juices.
Rapidly absorbed orally (max conc. 30-60 min in blood) Food interference (30 min before meal) Administered parenterally, in depot release preparations (procaine-penicillin, benzathine penicillin) |
penicillin G
(penicillin V is more stable in acid) |
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Inhibits the growth of penicillinase producing S. aureus
Relatively stable in an acid medium Absorbed rapidly but incompletely (30-80%) Eliminated rapidly by kidney. Also hepatic |
Isoxazoyl penicillin (oxacillin, cloxacillin, dicloxacillin)
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Very effective against S. aureus
Inactivated in the acidic medium |
Nafcillin
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β-lactamase sensitive
Acid stable Well-absorbed Food diminishes absorption Renal dysfunction prolongs half life |
Ampicillin
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β-lactamase sensitive
Acid stable Absorbed quickly; food does not interfere with absorption |
Amoxicillin
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MOA: inhibition of PBPs
Mechanisms of resistance: Altered PBP Beta lactamase (extended spectrum) Not active against Enterococci and L. monocytogenes Most are absorbed readily after oral administration Several can penetrate into CSF High concentrations achieved in synovial fluid, bile, pericardial fluid Primarily excreted by kidney Classified in 4 generations |
Cephalosporins
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Spectrum: good against Gram (+); modest against Gram (-)
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First generation cephalosporins
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Antianaerobe activity:
Cefoxitin, Cefmatazole, Cefotetan Increased activity against Gram (-) but much less active than IIIrd generation Gram (-) e.g. Klebsiella sp., Haemophilus influenzae |
Second generation cephalosporins
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Expanded Gram (-) coverage compared to 2nd generation
Some are able to cross BBB |
Third generation cephalosporins
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Cefepime
Good activity against: P. aeruginosa, Enterobacteriaceae, S. aureus, S. pneumoniae, Haemophilus, Neisseriae Penetrates in CSF More resistant to hydrolysis by chromosomal beta-lactamase |
Fourth generation cephalosporins
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MOA: Binds to PBPs, disrupting cell wall synthesis and is bactericidal.
Broad spectrum (P. aeruginosa sensitive too) Resistant to most forms of β-lactamase, including that produced by Staphylococcus Not absorbed orally Rapidly hydrolyzed by renal dipeptidase, so always administered with cilastatin, an inhibitor of dipeptidase |
imipenem
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Does not require cilastatin
Similar to imipenem but less likely to cause seizures |
meropenem
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MOA: Interacts with PBPs
Spectrum: No activity against Gram (+) and anaerobic bacteria are resistant. Aztreonam is resistant to the β-lactamase produced by Gram (-) organisms. Side effects: well tolerated. Penicillin allergic patients do not exhibit cross-reactions with aztreonam. |
aztreonam
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Inhibit β-lactamase (class A and D most sensitive to clavulanic acid)
Poor antimicrobial activity Included in combination with some beta-lactam antibiotics (amoxicillin) |
Clavulanic acid
Sulbactam |