Download Chapter 20, part A

TORTORA • FUNKE
• CASE
Microbiology
AN INTRODUCTION
EIGHTH EDITION
B.E Pruitt & Jane J. Stein
Chapter 20, part A
PowerPoint® Lecture Slide Presentation prepared by Christine L. Case
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Antimicrobial Drugs
• Chemotherapy
The use of drugs to treat a
disease
• Antimicrobial drugs
Interfere with the growth of
microbes within a host
• Antibiotic
Substance produced by a
microbe that, in small amounts,
inhibits another microbe
• Selective toxicity
A drug that kills harmful microbes
without damaging the host
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• Ehrlish the
magic bullet
• 1928 – Fleming
discovered
penicillin,
produced by
Penicillium.
• 1940 – Howard
Florey and
Ernst Chain
performed first
clinical trials of
penicillin.
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Figure 20.1
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Table 20.1
• Spectrum of antibiotics
• Narrow spectrum
• Broad spectrum
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Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Table 20.2
The Action of Antimicrobial Drugs
• Broad-spectrum
• Superinfection
• Bactericidal
• Bacteriostatic
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The Action of Antimicrobial Drugs
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Figure 20.2
The Action of Antimicrobial Drugs
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Figure 20.4
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
• Penicillin
• Natural penicillins
• Penicillin G excreted 3-6 hours
•Procine Penicillin stable 24 hours
•Benzathine Penicillin 4 month
•Penicillin V stable in stomach
• Semisynthetic penicillins
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Penicillins
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Figure 20.6
Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
• Penicillin
• Penicilinase-resistant penicillins
•Methicillin Oxacillin
• Extended-spectrum penicillins
• aminopenicillin like Carbenicillin
•Uridopenicillin like azocillin
• Penicillins + -lactamase inhibitors
• amoxicillin and calvulanic acid (Augmentin)
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Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
B lactam ring+thiazolidine ring
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Figure 20.8
• Carbapenems
•broadest antibacterial spectrum compared to other
beta-lactam classes such as penicillins.
•Meropenem
• Monobactam
•Aztreonam
•Synthetic antibiotics
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Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
dihydrothiazine ring
• Cephalosporins
• 2nd, 3rd, and 4th
generations more
effective against
gram-negatives
thiazolidine ring
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Figure 20.9
First generation
Cephazolin, cephalothin
Second generation
Cefaclore, cefuroxime
Third generation
Ceftriaxone, Ceftaxime, Ceftazidium
Fourth generation
Cefepime
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Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
• Polypeptide antibiotics
• Bacitracin
• Topical application
• Against gram-positives
• Vancomycin
• Glycopeptide
• Important "last line" against antibiotic resistant S.
aureus
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Antibacterial Antibiotics
Inhibitors of Cell Wall Synthesis
• Antimycobacterium antibiotics
• Isoniazid (INH)
• Inhibits mycolic acid synthesis
• Ethambutol
• Inhibits incorporation of mycolic acid
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Antibacterial Antibiotics
Inhibitors of Protein Synthesis
• Tetracyclines
• Broad spectrum
• bacteristatic,
• Interferes with tRNA attachment
• Tetracycline , deoxycycline, minocycline
• Act against intracellular bacteria as Rickettsia,
Chlamydia.
• Not used with children, pregnant women.
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• Aminoglycosides
• Streptomycin, neomycin, gentamycin
• Broad spectrum
• Changes shape of 30S sbuunit
• Gentamicin, Amikacin, Streptomycin most
common.
• Effect on kidney and auditory nerve.
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Antibacterial Antibiotics
Inhibitors of Protein Synthesis
• Chloramphenicol
• Broad spectrum, bacteriostatic
• Binds 50S subunit, inhibits peptide bond
formation
• Macrolides
• Gram-positives
• Binds 50S, prevents translocation
• Erythromycin
• Gram-positives
• Binds 50S, prevents translocation, bacteriostatic
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Antibacterial Antibiotics
Injury to the Plasma Membrane
• Polymyxin B
• Peptide derivatives
• One end of molecule water soluble and the other end
is hydrophobic.
• Topical
• Bactericidal
• Gram negative
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• Polyens
• amphotericin B and Nystatin The most important .
• Act against fungi by binding to ergosterol.
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Antibacterial Antibiotics
Inhibitors of Nucleic Acid Synthesis
• Rifamycin
• Inhibits RNA synthesis
• inhibits DNA-dependent RNA polymerase
• Anti tuberculosis
• Narrow spectrum Gram positive.
• Quinolones and fluoroquinolones
• Nalidixic acid, gram negative , UTI
• Ciprofloxacin, Broad spectrum, bactericidal
• Inhibits DNA gyrase
• Urinary tract infections
• Not used with children or pregnant
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Antibacterial Antibiotics
Competitive Inhibitors
• Sulfonamides (Sulfa drugs)
• Inhibit folic acid synthesis
• Broad spectrum
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Figure 5.7
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Figure 20.13
Disk-Diffusion Test
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Figure 20.17
E Test
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Figure 20.18
• MIC
Minimal inhibitory concentration
• MBC
Minimal bactericidal concentration
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Broth Dilution Test
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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.
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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.
• Autonomous or indifferent.
WHY!!!!!!!!!!!!!!!
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Who to choose antibiotics
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Figure 20.22
The Future of Chemotherapeutic Agents
• Antimicrobial peptides
• Broad spectrum antibiotics from plants and animals
• Disrupts permeability of microbial membrane.
• 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
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Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings