Chapter 33 Lecture Notes: Antimicrobial Therapy
Chapter 33 Lecture Notes: Antimicrobial Therapy
I. Chemotherapy
A. Definitions
1. Chemotherapy = treatment of a disease by a chemical compound selectively
directed against invading microbes or abnormal cells
2. Antibiotic = a microbial product or its derivative that kills or inhibits growth
of a susceptible organism
3. Antimicrobial = any agent that kills or inhibits growth of a susceptible
organism
B. History
1. early 1900s: Paul Erlich -Concepts of magic bullet and selective toxicity
2. Duchesne (1896) and Fleming (1928) and Florey and Chain (1939) –
penicillin
3. 1935: Gehard Domagk - sulfa drugs
4. 1944: Waksman - streptomycin
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3. Drug concentration in blood/body – via a variety of tests; important for
verifying agent has reached blood or other bodily areas in therapeutic
concentrations
C. Factors that influence effectiveness
1. mode of administration
a) oral – must survive acid
b) topical
c) parenteral – non-oral administration (i.e. injection)
2. access of site of infection
3. stability in body
4. susceptibility of pathogen
5. MIC – levels of drug at site must exceed MIC
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a) basic polypeptides that act as detergents
b) mechanism of action: interact with phospholipids to increase
permeability and decrease osmotic integrity à leakage on intracellular
components
c) bactericidal
d) gram –
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a) characterized by quinolone ring (Fig. 33-5)
b) mechanism of action: inhibits DNA gyrase à inhibition of DNA
replication (Fig. 33-6)
c) bactericidal
d) broad spectrum
2. rifampin
a) macrocyclic compound
b) mechanism of action: inhibits RNAP à inhibition of RNA synthesis
c) bactericidal
d) mostly gram +, some gram negatives
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a) only for appropriate infections
b) dual antibiotics
c) completion of treatment
d) narrow spectrum
2. Drug discovery
3. Rational drug design