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Distribution of Common Agents
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Basic steps for antimicrobial activity
- Direct interaction between the antibacterial agent and the cell
- Uptake (if activity is intracellular)
- Agent reaches adequate intracellular concentration
- Agent binds to target site
- Disruption of cellular process leading to inhibition of cell growth (bacteriostatic) or cell death (bactericidal)
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Bactericidal v. Bacteriostatic
- Bactericidal:
- Kill bacteria
- Used when the host defense mechanisms are impaired
- Required in endocarditis, kidney infection, osteo, meningitis
- Bacteriostatic:Inhibit bacteria
- Used when the host defense mechanisms are intact
- Used in many infectious diseases
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Bacteriostatic v. Bactericidal Examples
- Bacteriostatic:
- Erythromycin
- Clindamycin
- Tetracyclines
- Sulfonamides
- Trimethoprim
- Linezolid
- Bactericidal:
- Beta-lactams
- Vancomycin
- Aminoglycosides
- Quinolones
- Rifampin
- Metronidazole
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4 targets of antimicrobials
- cell wall synthesis(Peptidoglycan) (i.e. penicillins, cephalosporins)
- cell membrane (polymixin B)
- protein synthesis l(Ribosomes)(i.e. tetracyclines, chloramphenicol, macrolides, Lingcosamides, aminoglycosides)
- nucleic acid synthesis (sulfonamides, metronidazole, rifampin, fluoroquinolones
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Mechanisms of Bacterial Resistance
- 1. Antibiotic Inactivation
- - Enzymatic modification of antimicrobial
- - Common Examples: Beta lactamase activity or aminoglycoside inactivation
- 2. Alteration of the target site
- - Examples:
- Alteration of penicillin binding proteins (MRSA)
- DNA gyrase mutation results in fluoroquinolone resistance
- RNA polymerase mutation results in rifampin resistance
- 3. Interference with drug transport
- - The antimicrobial agent needs to first get inside the cell in order to have activity.
- - The bacteria’s own transport systems are used.
- 4. Metabolic bypass
- - A different product is made that bypasses the antibacterial action
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