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Antiobiotics vs Antimicrobial agents
- Antibiotics: natural substances produced by microbial organisms, used to inhibit/kill bacteria
- *now includes synthetic agents
- Antimicrobial agents: natural and synthesized substances that inhibit/kill a target organism (virus, fungi, etc)
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Bacteriostatic vs Bactericidal
- Bacteriostatic: inhibits growth
- Bactericidal: kills organism
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Narrow spectrum vs broad spectrum antibiotics
- Narrow spectrum: small group, specific type (G+)
- Broad spectrum: includes more groups (Haeomphilus, other GNR, anaerobes)
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What is extended spectrum beta-lactamase?
- Enzymes produced by G- to overcome antibiotics
- Grants resistance to penicillins, carbapenem drugs
- Plasmid-mediated (transferrable)
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What are the considerations for determining the proper antibiotic treatment?
- Will the drug reach the target area?
- Can it be concentrated at the site?
- Will it kill or inhibit the organism?
- Will it leave host cells unharmed?
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What are the BASIC antibiotic modes of action (Beta lactam, glycopeptide, polypeptide/lipopeptide, SXT, Quinolones, Aminoglycosides/macrolides, sulfonamides, trimethoprim)
- Beta lactam, glycopeptide: inhibit cell wall synthesis
- polypeptide/lipopeptides: inhibit cell membrane synthesis
- SXT, Quinolones: inhibition of DNA synthesis
- Aminoglycosides/macrolides: inhibition of protein synthesis
- sulfonamides, trimethoprim: metabolic pathway inhibitors
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Beta-Lactam structure and function
- four membered nitrogen-containing ring at core
- bind enzyme inhibiting transpeptidation ∴ inhibit cell wall synthesis
- cell wall weakened, leading to cell death
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Beta-lactam resistance
- Production of enzymes (eg beta-lactamases)
- 4 classes (Serine peptidases, Metallo-β-lactamases, cephalosporinases, serine peptidases)
- break the beta-lactam ring
- produce altered binding site (drug does not recognize)
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Beta-lactam examples + activity spectrum
- Penicillins: penicillin, ampicillin, oxacillin
- gram positive
- Cephalosporins: multiple generations with increasing spectrum
- broad, GNR
- carbapenems: imipenem, meropenem
- broad spectrum
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Glycopeptide structure and function
- large structure (can't fit through G- LPS)
- bind to the end of peptidoglycan, interfering with transpeptidation ∴ inhibit cell wall synthesis
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Cell membrane inhibitors function, last-resort drugs
- Act like detergents interacting w/ phospholipids to increase permeability (good against G- LPS)
- macromolecules/ions leak accross membrane
- more effective against G-
- Polymixin B and Colistin are last resort for P. aeruginosa and Acinetobacter
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Protein synthesis inhibitors function
- Target protein synthesis and severely disrupt cellular metabolism
- Bind 30S or 50S ribosomal subunits (not present in humans)
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Protein synthesis inhibitors examples
- Aminoglycosides, aminocyclitols
- marcolide-lincosamide-streptogramin group (MLS)
- ketolides
- oxazolidinones
- chloramphenicol (DRUG OF CHOICE, LOW TOXICITY)
- tetracyclines (low toxicity)
- Glycylglycines (low toxicity)
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Fluoroquinolones function
- bind to and interfere w/ DNA gyrase enzymes
- newer quinolones inhibit topoisomerase IV
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metronidazole function
- Nitro group is reduced in bacterial cytoplasm generating cytotoxic compounds that disrupt DNA
- *poison is hidden w/ nitro group that is used by bacteria
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rifamycin function
binds to DNA-dependent RNA polymeras and inhibits RNA synthesis
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sulfonamide function
- inhibits dihydropteroate synthase in the folic acid pathway
- *metabolic inhibitor
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trimethoprim function
- inhibits dihydrofolate reductase in the folic acid pathway
- *metabolic inhibitor
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nitrofuranitoin function
- drug intermediates bind to bacteria ribosomal proteins and rRNA (not well understood)
- *metabolic inhibitor
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Intrinsic vs acquired resistance
- intrinsic: natural genetic make-up of WT organism
- acquired: resistance after previous susceptibility
- mutation, acquisition (plasmid)
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Describe various methods of intrinsic/acquired resistance
- intrinsic
- Cell wall permeability (eg. GNR resistant to glycopeptides)
- efflux (pumped out)
- biofilm formation (can't penetrate)
- gene expression to inactivate antibiotic
- acquired
- modification to target site
- enzyme inactivation of antibiotic
- efflux
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4 ways that resistance can emerge
- New resistance genes
- Spread of old resistance genes
- Mutation of old resistance genes
- Emergence of intrinsically resistant bacteria (Stenotrophomonas)
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What is mecA?
- The gene that codes for altering of binding site in MRSA
- Predicts resistance for all beta lactam drugs
- can be detected by screeing plate/latex test
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What is inducible resistance?
Erythromycin discs near clindamycin discs can induce resistance to clindamycin in an organism
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