Antibiolotics And Antibiotic Resistance Flashcards
• A type of antimicrobial agent
• Used to treat bacterial infections
• Produced naturally by microorganisms
• Semi-synthetic, fully-synthetic
• Two types based on activity
• Bactericidal
• Bacteriostatic
• Two classes based on spectrum of activity
• Broad spectrum
• Active against many different types of bacteria
• Narrow spectrum
• Active against specific organisms
• Five classes based on mechanisms of action
Antibiotics
Inhibition of cell wall synthesis
• Targets peptidoglycan synthesis
• Cell lysis
• Disruption of cell membrane integrity
• Increases permeability
• lon leakage and cell death
• Inhibition of protein synthesis
• Targets bacterial ribosomes (only)
• Blocks translation
• Inhibition of nucleic acid synthesis
• Interferes with DNA replication or transcription
• Inhibition of essential metabolic pathways
• Inhibits key biosynthetic enzymes Inhibition of cell wall synthesis
• Targets peptidoglycan synthesis
• Cell lysis
• Disruption of cell membrane integrity
• Increases permeability
• lon leakage and cell death
• Inhibition of protein synthesis
• Targets bacterial ribosomes (only)
• Blocks translation
• Inhibition of nucleic acid synthesis
• Interferes with DNA replication or transcription
• Inhibition of essential metabolic pathways
• Inhibits key biosynthetic enzymes
Mechanisms of action
• Penicillins, e.g., penicillin G
• Broad spectrum
• Anaphylaxis in hypersensitive individuals
• Cephalosporins, e.g., ceftriaxone
• Multiple generations
• Carbapenems, e.g., imipenem
• Reserved for multidrug-resistant (MDR) infections
• Resistant to B-lactamases
• Monobactams, e.g., aztreonam
• Narrow spectrum for aerobic Gram-negative bacteria
• B-lactam not fused with thiazole ring
Inhibition of cell wall synthesis
• Polymyxins, e.g., polymyxin B
• Peptides
• Narrow spectrum
• Gram-negative
• Multidrug-resistant organisms
• Side effects
• Nephrotoxicity • Polymyxins, e.g., polymyxin B
• Peptides
• Narrow spectrum
• Gram-negative
• Multidrug-resistant organisms
• Side effects
• Nephrotoxicity
Disruption of cell membrane
Tetracyclines, e.g., tetracycline
• Targets 30S ribosomal subunit
• Bacteriostatic
• Broad spectrum
• Effective for intracellular organisms
• Not used for children and pregnant women
• Aminoglycosides, e.g., gentamicin
• Targets 30S ribosomal subunit
• Narrow spectrum
НзС.
• Gram-negative
• Naturally resistant organisms
• Nephrotoxicity/ototoxicity
Macrolides, e.g., erythromycin
• Targets 50S ribosomal subunit
• Bacteriostatic
• Broad spectrum
• Used when allergic to B-lactams
• Chloramphenicol
• Targets 50S ribosomal subunit
• Broad spectrum
• Side effects
• Bone marrow suppression
• Used when not responding to safer antibiotics
Inhibition of protein synthesis
Quinolones, e.g., ciprofloxacin
• Inhibits DNA gyrase/topoisomerase
• Multiple generations
• Broad spectrum
• Side effects
• Affects tendons and cartilages
• Psychiatric symptoms
• Rifamycins, e.g., rifampin (rifampicin)
• Inhibits RNA polymerase
• Effective against mycobacteria
• Reserved for tuberculosis
• Also used for leprosy
• Resistance develops quickly
• see in comonation
• Hepatotoxicity
Inhibition of nucleic acid synthesis
• Sulfonamides, e.g., sulfamethoxazole
• Inhibits folic acid synthesis
• Dihydropteroate synthetase
• Bacteriostatic
• Broad spectrum
• First to be used systemically
• Allergic reactions
• Trimethoprim
• Inhibits folic acid synthesis
• Dihydrofolate reductase
• High selectivity
• Bacteriostatic
• Used in combination with sulfonamides
Inhibition of essential metabolic pathways
Bacteria may be resistant to antibiotics
• nnate fintrinsic› resistance
• E.g., gentamicin vs streptococci
• Acquired resistance
• Two ways to acquire resistance
• Mutations
• From other organisms (horizontal gene transfer)
• Plasmid-mediated
• Through transposons (jumping genes)
• Cross resistance vs dissociate resistance
• Mechanism of drug action + resistance mechanism
Antibiotic resistance
Enzymatic inactivation of antibiotics
• Bacterial enzymes degrade or modify antibiotics
• B-lactamases - B-lactams (activity restored with tazobactam)
• Aminoglycoside-modifying enzymes
• Alternation of the antibiotic target
• Mutations or modifications reduce drug binding affinity
• Ribosomal modifications - macrolides
• Mutations in DNA gyrase or topoisomerase - fluoroquinolones
Efflux pumps
• Transporters expel antibiotics from the bacterial cell
• Multidrug efflux pumps - tetracyclines, macrolides, fluoroquinolones
• Tet efflux pumps - specific for tetracyclines
Decreased uptake of antibiotics
• Changes in outer membrane or cell wall structures limit antibiotic entry
• Loss/modification of porins - B-lactams, fluoroquinolones
• Thickened peptidoglycan layer - vancomycin (VRE)
Bypassed or alternative metabolic pathways
• Alternative biochemical pathways evade antibiotic action
• Plasmid-mediated Sul enzymes - sulfonamides
Mechanisms of resistance
• Increased occurrence of resistance
• Selective pressure
• Exposure select for resistant bacteria
Use and inappropriate use
• Use in human and animal medicine
• Use as prophylaxis in farm animals
• Use to promote growth of farm animals
• Consequences of antibiotic resistance
• Treatment failures in bacterial infections
• 1.3 million deaths globally (2019)
• Inability to perform routine medical procedures
• Major economic burden on society
Antibiotic use and resistance
