Antimicrobial Drugs
• Chemotherapy: Use of chemicals that
do not harm the host yet kills others.
• Chemotherapeutic agent: substance
that is used in medicine.
• Antimicrobial agents: Chemicals
used to treat diseases caused by
microbes.
• Antibiotics: Produced by microbes to
inhibit others
• Synthetic drugs: Antimicrobials made
in the lab
• Semi Synthetic: synthetic or natural
that is modified in the lab.
History of Antibiotics
• Paul Ehrlich- Sulfa that stains bacteria
may be able to inhibit it as well. Predicted
the rise of antimicrobials
• 1928 Fleming makes his observation
• 1940’s production of penicillin
• In order to keep up with microbial
resistance we must continually discover
new antibiotics, but this is getting harder to
do
• 1928 – Fleming
discovered
penicillin,
produced by
Penicillium.
• 1940 – Howard
Florey and Ernst
Chain performed
first clinical trials
of penicillin.
Figure 20.1
Drug Discovery
Figure 20.1
General Properties of
antimicrobials
• Selective toxicity: Kills microbes not host
• Has a spectrum of activity
– Broad
– Narrow
– Which is better?
– Why?
Table 20.2
The Action of Antimicrobial
Drugs
Figure 20.2
Modes of action
• Inhibition of cell wall synthesis
– Pen
• Disruption of cell membrane function
– Polymyxins
• Inhibition of protein synthesis
– Chloramphenicol
– Erythromycin
– Tetracycline
– Streptomycin
The Action of Antimicrobial
Drugs
Figure 20.4
• Inhibition of nucleic acid synthesis
– Rifamycin
• Inhibitors of enzymatic function of primary
metabolism
– Competitive inhibition
– Noncompetitive inhibition
Competitive Inhibitors
– Sulfonamides (sulfa
drugs)
 Inhibit folic acid synthesis
 Broad spectrum
Figure 5.7b
Figure 20.13
Side Effects
•
•
•
•
Toxicity in host
Allergy in host
Disruption of normal microbiota
Birth defects in pregnancy
Resistance of microbes
• When microbes no longer respond to an
antibiotic
• Resistance is acquired by
– Non genetic means, basically evasion, grow
in an area not exposed to antibiotic
• Tuberculosis
– Genetic resistance
• A change in the chromosome or gain of a plasmid.
Antibiotic Resistance
• A variety of mutations can lead to antibiotic
resistance.
• Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug
• Resistance genes are often on plasmids or
transposons that can be transferred between
bacteria.
• We humans will always have to find or
create new antibiotics as microbes
become resistant
8 Attributes of an ideal
antimicrobial agent
1.
2.
3.
4.
5.
6.
7.
8.
Solubility in body fluids
Selectively toxic
Toxicity not easily altered
Not allergenic
Stability in body
Resistance not easily acquired
Long shelf life
Reasonable cost
• Drugs with all 8 characteristics are very
very rare.
Inhibitors of cell wall Synthesis
•
•
•
•
Ampicillin
Cephalosporin
Bacitracin
Vancomycin
Inhibitors of Protein Synthesis
•
•
•
•
Streptomycin
Tetracycline
Clormphenicol
Erythromycin
Plasma membrane
• Polymyxin B
Inhibitors of Nucleic Acid Synthesis
• Rifampin
• ciprofloxacin
Competitive inhibitors of the
Synthesis of Essential Metabolites
• Trimethoprim-sulfamethoxozole
Antifungal
• Amphotericin B
• Griseofulvin
• Flucytosine
Antiviral drugs
•
•
•
•
Acyclovir
Ganciclovir
Indinavir
Alpha interferon
Antiprotozoan Drugs
• Chloroquine
• Diiodohydroxyquin
• Metronidazole
Antihelminthic Drugs
• Niclosamide
• What are these drugs, modes of action
and side effects?
Nucleoside and Nucleotide
Analogs
Figure 20.16b ,c
Tests to Guide Chemotherapy
• MIC: Minimal inhibitory concentration
• MBC: Minimal bactericidal concentration
• Antibiogram
Broth Dilution Test
Figure 20.19
Resistance to Antibiotics
Figure 20.20
From Lab
• How do antimicrobials work
• How are they tested?
Effects of Combinations of
Drugs
Figure 20.22
Effects of Combinations of Drugs
• Synergism occurs when the effect of two
drugs together is greater than the effect of
either alone
• Antagonism occurs when the effect of
two drugs together is less than the effect
of either alone
Disk-Diffusion Test
Figure 20.17
Future of Chemotherapeutic
Agents
• Antimicrobial peptides
– Broad-spectrum antibiotics
• Nisin (lactic acid bacteria)
• Magainin (frogs)
• Cecropin (moths)
Future of Chemotherapeutic
Agents
• Antisense agents
– Complementary DNA that binds to a pathogen's
virulence gene(s) and prevents transcription
– Fomivirsen to treat CMV retinitis
Future of Chemotherapeutic
Agents
• siRNA
– Complementary
RNA that binds
mRNA to inhibit
translation
Figure 9.14