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Antimicrobial Drugs. ChemotherapyThe use of drugs to treat a disease Antimicrobial drugsInterfere with the growth of microbes within a host AntibioticSubstance produced by a microbe that, in small amounts, inhibits another microbe

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Antimicrobial Drugs

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Antimicrobial drugs l.jpg

Antimicrobial Drugs

  • ChemotherapyThe use of drugs to treat a disease

  • Antimicrobial drugsInterfere with the growth of microbes within a host

  • AntibioticSubstance produced by a microbe that, in small amounts, inhibits another microbe

  • Selective toxicityA drug that kills harmful microbes without damaging the host


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  • 1928 – Fleming discovered penicillin, produced by Penicillium.

  • 1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin.

  • All three were awarded the Nobel Prize in Medicine in 1945

Figure 20.1


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Many Antibiotics come from Bacterial or Fungal Sources

Table 20.1


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Table 20.2


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The Action of Antimicrobial Drugs

  • Disrupt Cell Wall synthesis or through damage

  • Disrupt Proteins synthesis

  • Disrupt Nucleic Acid synthesis or function

  • Disrupts essential metabolic enzymes-usually by competitive inhibition.


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The Action of Antimicrobial Drugs

Figure 20.2


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The Action of Antimicrobial Drugs

Figure 20.4


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Penicillins

Figure 20.6


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Penicillinase Enzyme Allows Bacteria to be Resistant to Penicillin

Figure 20.8


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Other Inhibitors of Cell Wall Synthesis

  • Cephlosporins-used Penicillin structure to synthesize antibiotics more effective on Gram Negative bacteria

  • Polypeptide antibiotics

    • Bacitracin

      • Topical application

      • Against gram-positives

    • Vancomycin

      • Glycopeptide

      • Important "last line" against antibiotic resistant S. aureus


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Other Inhibitors of Cell Wall Synthesis

  • Antimycobacterium antibiotics (TB, Leprosy)

    • Isoniazid (INH)

      • Inhibits mycolic acid synthesis

    • Ethambutol

      • Inhibits incorporation of mycolic acid


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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


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Inhibitors of Protein Synthesis

  • Tetracyclines

    • Broad spectrum

      • Interferes with tRNA attachment

  • Erythromycin

    • Gram-positives

      • Binds 50S, prevents translocation

Injury to the Plasma Membrane

  • Polymyxin B

    • Topical

    • Combined with bacitracin and neomycin in over-the-counter preparation


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Inhibitors of Nucleic Acid Synthesis

  • Rifamycin

    • Inhibits RNA synthesis

    • Antituberculosis

  • Quinolones and fluoroquinolones

    • Ciprofloxacin

    • Inhibits DNA gyrase

    • Urinary tract infections


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Competitive Inhibitors

  • Sulfonamides (Sulfa drugs)

    • Inhibit folic acid synthesis

    • Broad spectrum

Figure 5.7


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Figure 20.13


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Antifungal DrugsInhibition of Ergosterol Synthesis

  • Ergosterol important part of fungal cell wall. Unique to fungi, therefore a good drug target

Inhibition of Cell Wall Synthesis

  • Echinocandins

    • Inhibit synthesis of -glucan


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Antifungal DrugsInhibition of Nucleic Acids

  • Flucytocine

    • Cytosine analog interferes with RNA synthesis

Antifungal DrugsInhibition of Microtubules (Mitosis)

  • Tolnaftate

    • Used for athlete's foot; action unknown


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Antiviral DrugsNucleoside and Nucleotide Analogs

Figure 20.16a


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Antiviral DrugsNucleoside and Nucleotide Analogs

Figure 20.16b, c


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Antiviral Drugs: Enzyme Inhibitors

  • Protease inhibitors

    • Indinavir

      • HIV

  • Inhibit attachment

    • Zanamivir

      • Influenza

Antiprotozoan Drugs

  • Chloroquine

    • Inhibits DNA synthesis

      • Malaria


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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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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


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Disk-Diffusion Test

Figure 20.17


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Chemical Methods of Microbial Control

  • Evaluating a disinfectant

    • Disk-diffusion method

Figure 7.6


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  • MIC Minimal inhibitory concentration

  • MBC Minimal bactericidal concentration


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E Test

Figure 20.18


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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.


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Effects of Combinations of Drugs

Figure 20.22


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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


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