Antibacterial Agents 1: Introduction Flashcards
Selective Toxicity
Drugs should affect microbe, not host, by taking advantage of biochemical differences
Folate Metabolism, Protein Synthesis, Nucleic Acid Synthesis, Cell Wall, Fungal Cell Membrane
Antibiotic resistance
Natural
The bugs just don’t have the drug target (Fungi don’t have peptidoglycan cell walls)
Antibiotic Resistance
Escape
Organism escapes consequences because of resource availability, or failure to lyse because of little osmotic pressure difference
Antibiotic Resistance
Acquired
Mutational resistance vs. Plasmid mediated resistance
Antibiotic Resistance
Acquired
Mutational
Basic chromosomal mutations over several generations
Proper dosing and duration of atbx prevents survival of slight resistance strains
Antibiotic Resistance
Acquired
Plasmid Mediated/Genetic Transfer
Resistance conferred by plasmids
Can be a source of multiple drug resistance in a single treatment course
Conjugation, Transduction and transformation
Mechanism of Resistance
Altered Targets
Examples:
DNA Gyrase (fluoroquinolones)
Penicillin-Binding Proteins (Beta-lactam antibiotics)
Mechanism of Resistance
Enzymatic Destruction
Examples:
B-lactamase (B-lactam atbx)
Acetyltransferase (chloramphenicol)
Mechanism of Resistance
Alternative resistant metabolic pathways
Overproduction of PABA or thymidine nucleotides (against sulfonamides)
Mechanism of Resistance
Decreased Entry
Normally natural resistance
Against B-lactams, flruoroquinolones, aminoglycosides
Mechanism of Resistance
Increased Efflux
Against: Tetracyclines, fluoroquinolones, macrolides
Bactericidal Mechanisms
Inhibition of Cell wall
Membrane disruption
DNA function/Synthesis interference
Bacteriostatic Mechanisms
Inhibition of protein syntehsis
Inhibition of intermediary metabolic pathways
Bactericidal agents are preferred in
Severe infections
Bactericidal agents act ______ and their action is often _____
Quickly, irreversible
Bactericidal agents can ______ for patients with an impaired host defense
Compensate
actericidal agents are required
for treatment of infections in locations that are ________
Not accessible to the host immune response
Atbx Absoprtion
Typically Oral or IV, some topical. Oral preferred
Atbx Distribution
Readily Enter CSF
Chloramphenicol
Sulfonamides
Cephalosporins (3rd and 4th)
Rifampin
Atbx Distribution
Enters CSF with Inflammation
Penicillins
Vancomycin
Ciproflaxocin
Tetracyclin
Atbx Distribution
Enters CSF Poorly
Aminoglycosides
Cephalosporins (1st and 2nd)
Erythromycin
Clindamycin
Fetal Effects
Drugs that can be taken orally (have the ability to cross the gastric mucosal barrier) can also cross the placenta
Post-Antibiotic Effect
Some antibiotics (aminoglycosides and fluoroquinolones) continue to kill/inhibit after the [drug] goes below MIC
Antibiotic spectrum
Narrow (Definition)
Most effective on susceptible organism
Antibiotic spectrum
Narrow (Drugs)
Gram (+) or (-)
Aminoglycosides Penicillinase-resistant Penicillins Clindamycin Vancomycin Metronidazole Penicillin G, V
Antibiotic Spectrum
Extended (Drugs)
Gram (+) and (-)
Aminopenicillins
Cephalosporins
Fluoroquinolones (Cip, levo)
Carbapenems
Antibiotic Spectrum
Broad (definition)
Greater scope of activity for initial coverage, more likely to cause superinfections
Antibiotic Spectrum
Broad (Drugs)
Macrolides Chloramphenicol Fluoroquinolones (Moxi, Gemi) Sulfonamides Tetracyclines Trimethoprim
Cell Wall inhibition
Stage 1 Alanine Racemase:
Cycloserine
Enolpyruvate transferase
Fosfomycin
Cell Wall inhibition
Stage 2 d-ala-d-ala pentapeptide
Vancomycin
Bactoprenol lipid carrier
Bacitracin
Cell Wall inhibition
Stage 3 Transpeptidase
Penicillins
Cephalosporins
Monobactams
Carbapenams
Inhibition/Damage to Cell Membrane
Daptomycin, polymixin B
Modification of synthesis/metabolism of Nucleic Acids
DNA Gyrase
Fluoroquinolones
Modification of synthesis/metabolism of Nucleic Acids
RNA Polymerase
Rifampin
Modification of synthesis/metabolism of Nucleic Acids
DNA
Metronidzaole
Nitrofurantoin
Inhibition/Modification of protein synthesis
30S Ribosome
Aminoglycosides
Tetracyclines
Inhibition/Modification of protein synthesis
50S Ribosome
Clindamycin
Macrolides
Chlorampehnicol
Streptogramins
Modification of intermediary metabolism
Dihydropteroate SYnthase
Sulfonamides
Modification of intermediary metabolism
Dihydrofolate reductase
Trimethoprim
