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Antimicrobial Drugs PowerPoint PPT Presentation


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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

  • 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


  • 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


Many Antibiotics come from Bacterial or Fungal Sources

Table 20.1


Table 20.2


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.


The Action of Antimicrobial Drugs

Figure 20.2


The Action of Antimicrobial Drugs

Figure 20.4


Penicillins

Figure 20.6


Penicillinase Enzyme Allows Bacteria to be Resistant to Penicillin

Figure 20.8


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


Other Inhibitors of Cell Wall Synthesis

  • Antimycobacterium antibiotics (TB, Leprosy)

    • Isoniazid (INH)

      • Inhibits mycolic acid synthesis

    • Ethambutol

      • Inhibits incorporation of mycolic acid


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


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


Inhibitors of Nucleic Acid Synthesis

  • Rifamycin

    • Inhibits RNA synthesis

    • Antituberculosis

  • Quinolones and fluoroquinolones

    • Ciprofloxacin

    • Inhibits DNA gyrase

    • Urinary tract infections


Competitive Inhibitors

  • Sulfonamides (Sulfa drugs)

    • Inhibit folic acid synthesis

    • Broad spectrum

Figure 5.7


Figure 20.13


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


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


Antiviral DrugsNucleoside and Nucleotide Analogs

Figure 20.16a


Antiviral DrugsNucleoside and Nucleotide Analogs

Figure 20.16b, c


Antiviral Drugs: Enzyme Inhibitors

  • Protease inhibitors

    • Indinavir

      • HIV

  • Inhibit attachment

    • Zanamivir

      • Influenza

Antiprotozoan Drugs

  • Chloroquine

    • Inhibits DNA synthesis

      • Malaria


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


Disk-Diffusion Test

Figure 20.17


Chemical Methods of Microbial Control

  • Evaluating a disinfectant

    • Disk-diffusion method

Figure 7.6


  • MIC Minimal inhibitory concentration

  • MBC Minimal bactericidal concentration


E Test

Figure 20.18


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


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