Antimicrobial Drugs
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Transcript Antimicrobial Drugs
Antimicrobial Drugs
Antimicrobial Drugs
Chemotherapy
Antimicrobial drugs Interfere with
the growth of microbes within a host
Antibiotic
The use of drugs to treat a disease
Substance produced by a microbe that, in
small amounts, inhibits another microbe
Selective toxicity
A drug that kills harmful microbes without
damaging the host
Historical Perspective
Treatment hopeless before 1935
Paul Ehrlich, early 20th century
Father of chemotherapy
Penicillin discovered -- gram positives
Penicillin -- first therapeutic use
Streptomycin -- gram negatives
Fleming -- 1929
Florey -- 1940
Waksman -- 1944
1947 -- Chloramphenicol -- broad spectrum
1947 - present -- many
1928 – Fleming
discovered
penicillin,
produced by
Penicillium.
1940 – Howard
Florey and
Ernst Chain
performed first
clinical trials of
penicillin.
Figure 20.1
Properties of an ideal antibiotic
broad spectrum
stable--long shelf life
soluble in body fluids
stable toxicity
Nonallergenic
reasonable cost
selectively toxic
not likely to induce bacterial resistance
Major genera that produce clinically
useful antibiotics
Bacillus
Streptomyces
Cephalosporium
Penicillium
Major targets of antimicrobial activity
Cell wall synthesis
penicillins, cephalosporins (beta-lactamase producing
bacteria resistant to both, require active cell wall
synthesis in actively growing cultures), bacitracin
Cell membrane function
amphotericin B (no growth requirement, changes membrane
permeability by binding to sterols in fungal membranes,
more side effects since membranes similar in all cells)
Protein synthesis
Aminoglycides, tetracyclines, chloramphenicol
Major targets of antimicrobial activity
DNA synthesisTranslation (mRNA--> protein):
Transcription: rifampin (TB), actinomycin D
Block movement of ribosome along mRNA: streptomycin,
tetracycline
Prevent peptide bond formation by binding to ribosome:
chloramphenicol, erythromycin
Antimetabolites (structural analogs of natural substances
important in metabolism): PASA, sulfa drugs, INH
PASA very similar in structure to PABA, required by bacteria
(but not human cells) for synthesis of folic acid
When PASA is used in synthesis of folic acid, results in
nonfuctional folic acid analog and bacterial cell dies
Spectrum of Activity
The Action of Antimicrobial Drugs
The Action of Antimicrobial
Drugs
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
Penicillin
Natural penicillins
Semisynthetic penicillins
Penicilinase-resistant penicillins
Extended-spectrum penicillins
Penicillins + -lactamase inhibitors
Carbapenems
Monobactam
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
Cephalosporins
2nd, 3rd, and 4th generations more effective against
gram-negatives
Polypeptide antibiotics
Bacitracin
Topical application
Against gram-positives
Vancomycin
Glycopeptide
Important "last line" against antibiotic resistant S.
aureus
Antibacterial Antibiotics
Inhibitors of Protein Synthesis
Chloramphenicol
Broad spectrum
Binds 50S subunit, inhibits peptide bond formation
Aminoglycosides
Streptomycin, neomycin, gentamycin
Broad spectrum
Changes shape of 30S subunit
Antibacterial Antibiotics
Inhibitors of Protein Synthesis
Tetracyclines
Broad spectrum
Macrolides
Gram-positives
Interferes with tRNA attachment
Binds 50S, prevents translocation
Erythromycin
Gram-positives
Binds 50S, prevents translocation
Disk-Diffusion Test
Figure 20.17
Definitions
MIC
Minimal inhibitory
concentration
MBC
Minimal bactericidal
concentration
Broth Dilution Test
Figure 20.19
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.
Antibiotic Resistance
Misuse of antibiotics selects for
resistance mutants. Misuse includes:
Using outdated, weakened antibiotics
Using antibiotics for the common cold and
other inappropriate conditions
Use of antibiotics in animal feed
Failure to complete the prescribed regimen
Using someone else's leftover prescription
Figure 20.20
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.
Effects of Combinations of
Drugs
Figure 20.22
The Future of
Chemotherapeutic Agents
Antimicrobial peptides
Broad spectrum antibiotics from plants and
animals
Squalamine (sharks)
Protegrin (pigs)
Magainin (frogs)
Antisense agents
Complementary DNA or peptide nucleic acids
that binds to a pathogen's virulence gene(s)
and prevents transcription