I. Development of Antimicrobial Chemotherapy
B. Herbal cures
C. Paul Ehrlich (1907)
D. Alexander Fleming (1928)
E. G. Domagk (1935)
F. Howard Florey and Ernst Chain (1939)
II. General Characteristics
A. Sources of antimicrobial agents
1. plant extracts
2. chemicals
3. antibiotics
4. synthetic and semi-synthetic
B. Spectrum
1. narrow spectrum
2. broad spectrum
C. Nomenclature
1. class name
e.g. cephalosporin
2. chemical name
| 3-{[(5-methyl-1,3,4-thiadiazol-2-yl) thio]-methyl} 8-oxy- 7-[2-(1H-tetrazol-1-yl) acetamido]-5-thia-1-azabicyclo [42.0] oct-2-ene-2-carboxylic acid |
3. generic name
cefazolin
4. trade name
Ancef (Smith Kline & French)
Kefzol (Lily)
D. Uses of Antimicrobial agents
1. therapeutic treatment
2. empiric treatment
3. prophylactic treatment
III. Antimicrobial Susceptibility Testing
A. Dilution susceptibility tests
minimal inhibitory concentration (MIC)
1. agar dilution
2. broth dilution
B. Disk diffusion
Kirby-Bauer
IV. Modes of Action of Antimicrobial Agents
A. Inhibition of cell wall synthesis
1. activity
narrow and
broad spectrum
2. examples
penicillins,
cephalosporins, bacitracin, piperacillin, etc.
B. Inhibition of protein synthesis
1. activity
most are
broad spectrum
2. examples
tetracyclines,
aminoglycosides (streptomycin), chloramphenicol, erythromycin, nitrofurantoin
C. Injury to cell membrane
1. activity
most are narrow spectrum
2. example
polymixins
D. Inhibitors of nucleic acid synthesis/function
1. activity
most are
broad spectrum
2. examples
trimethoprim,
quinolones, rifampin
E. Antimetabolites
1. activity
interfere with synthesis of essential microbial compound by mimicing the substrate
most are
narrow spectrum
2. examples
sulfonamides,
isoniazid
V. Drug Resistance
A. Mechanisms of drug resistance
1. production of an enzyme to inactivate the antimicrobial agent
penicillinase
2. alteration of target (binding) site
penicillin
binding proteins
3. alteration in permeability to agent
tetracyclines
4. production of an alternate metabolic pathway
sulfonamides
B. Transfer of drug resistance
1. R plasmids
2. conjugation
3. transduction
4. spontaneous mutation
C. Selection of drug resistant strain
D. Measures to help prevent drug resistance
1. prescribe proper medication
2. patient compliancy
3. keep new drugs in reserve
4. limit antimocrobial agents use in agriculture
5. improve product labeling
VI. Antifungal Drugs
A. Fungal infections are more difficult to treat
B. Examples
nystatin, griseofulvin, amphotericin
B, imidazoles
VII. Antiviral Agents
A. Also very difficult to treat viral infections
B. Examples
amantadine, adenine arabinoside,
acyclovir, azidothymidine (AZT)