Block 2 Flashcards
Disinfectants
Toxic to humans and bacteria (Bleach)
Nonspecific
Used to eliminate organisms on inanimate objects
Antiseptics
Generally toxic to bacteria
Nonspecific effects
too toxic for systemic use in humans (e.g. peroxides, alcohol)
OK for topical use
Antibiotics
Targets specific cellular processes
exhibit effects on bacteria but not humans- selective toxicity
con be administered systemically
Bacteriostatic
inhibit growth of bacteria (but do not kill them) - rely on immune to eradicate
Bactericidal
kill bacteria directly - important for immunocompromised patients
Spectrum of activity
the collection of bacterial species that is susceptible to a given antibiotic
Narrow Spectrum: effective against a small group of bacteria (e.g. aerobic gram-positive bacteria)
Broad spectrum: effective against a wide range of bacteria (e.g. gram-positive and gram-negative bacteria)
Minimum inhibitory concentration (MIC)
defines lowest concentration that inhibits growth of bacteria
Minimum bactericidal concentration (MBC)
Defines lowest concentration of antibiotic that kills a defined proportion of bacterial population after a specified time (e.g. 99.9% of bacteria killed after 24 h)
Horizontal gene transfer
acquisition of foreign DNA encoding resistance genes; can enable rapid emergence of multi-drug resistant strains
3 Basic mechanisms of resistance
Modification (inactivation) of antibiotic molecule itself
Modification (reprograming) of antibiotic target
Reduction of antibiotic concentration/prevent access to target
Antibiotics that target peptidoglycan synthesis
B-Lactams
Vancomycin
Bacitracin
Antibiotics that target Ribosomes and protein synthesis
Tetracyclines
Aminoglycosides
Macrolides
Oxazolidinones
Antibiotic that target DNA replication and repair
Fluoroquinolones
Antibiotics that target key metabolic reactions
Trimethoprim
sulfamethoxazole
Antibiotics that target the cell membrane
Polymyxin
Daptomycin
B-Lactams
Block peptidoglycan crosslinking by binding PBPs and inactivating them
Structure of B-Lactam mimics the natural substrate for PBP
Resistance:
B-lactamase cleaves b-lactam ring of antibiotic, rendering it inactive
Mutations in PBPs
Clavulanic Acid
B-Lactamase inhibitor
Contains a B-lactam ring
Binds to b-lactamase
Glycopeptides (vancomycin)
Binds to D-ala-D-ala at the end of peptide side chain in peptidoglycan precursor, blocking PBP
Effective on Gram-Positive (but not Gram-Negative)
Used for B-lactam resistant infections
Vancomycin resistance occurs when the bacteria alters D-ala-D-ala to D-ala-D-lac; Vaconmycin is no longer able to bind
Cycloserines
Inhibit peptidoglycan crosslinking
Competitive inhibitor of D-alanine:
alanine racemase
D-alanyl-D-alanine synthetase
Bacitracin
peptide antibiotic - too toxic for systemic use
binds to pyrophosphate on the lipid carrier for peptidoglycan precursors and blocks its recycling
Daptomycin
agent against the cells envelope
Bactericidal, narrow spectrum (gram-positive bacteria)
Polymyxins
agent against the cell envelope
Bactericidalm narrow spectrum (gram-negative)
binds to LPS in outer membrane
Tetracycline
Protein synthesis inhibitor: targets 30S function
Bacteriostatic, broad spectrum
binds 30S subunit and interferes with the binding of tRNA
Resistance: tetracycline efflux pumps (most common), mutations on ribosomes
Aminoglycosides
Bactericidal, broad spectrum
binds irreversibly to 30S and causes misreading
useful for hard-to-kill gram-negative
do not penetrate many gram-positive
Macrolides
(erythromycin, azithromycin, clarithromycin)
Bacteriostatic, Primarily active against gram-positive bacteria
Binds 50S subunit and blocks elongation of proteins
Resistance:
enzymatic methylation of ribosomal RNA
Efflux pumps
