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TORTORA • FUNKE • CASE Microbiology AN INTRODUCTION EIGHTH EDITION B.E Pruitt & Jane J. Stein Chapter 20, part B Antimicrobial Drugs Antifungal Drugs Inhibition of Ergosterol Synthesis • Polyenes • Amphotericin B • Azoles • Miconazole • Triazoles • Allylamines Figure 20.15 Antifungal Drugs Inhibition of Cell Wall Synthesis • Echinocandins • Inhibit synthesis of -glucan • Cancidas is used against Candida and Pneumocystis Antifungal Drugs Inhibition of Nucleic Acids • Flucytocine • Cytosine analog interferes with RNA synthesis • Pentamidine isethionate • Anti-Pneumocystis; may bind DNA Antifungal Drugs Inhibition of Microtubules (Mitosis) • Griseofulvin • Used for superficial mycoses • Tolnaftate • Used for athlete's foot; action unknown Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16a Acyclovir Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16b, c Antiviral Drugs Enzyme Inhibitors • Protease inhibitors • Indinavir • HIV • Inhibit attachment • Zanamivir • Relenza • Inhibit uncoating • Amantadine • Oseltamivir • Tamiflu • Interferons prevent spread of viruses to new cells • Viral hepatitis Antiprotozoan Drugs • Chloroquine • Inhibits DNA synthesis • Malaria - may require Malarone • Diiodohydroxyquin • Unknown • Amoeba • Metronidazole • Damages DNA • Entamoeba, Trichomonas Antihelminthic Drugs • Niclosamide • Prevents ATP generation • Tapeworms • Praziquantel • Alters membrane permeability • Flatworms • Pyantel pamoate • Neuromuscular block • Intestinal roundworms Antihelminthic Drugs • Mebendazole • Inhibits nutrient absorption • Intestinal roundworms • Ivermectin • Paralyzes worm • Intestinal roundworms Evaluation of Antimicrobials-Disk-Diffusion Test Figure 20.17 MIC and MBC Action on growth after transfer to new media • MIC Minimal inhibitory concentration • MBC Minimal bactericidal concentration Broth Dilution Test Figure 20.19 Figure 20.20 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 Misuse includes: • Using outdated, weakened antibiotics • Using antibiotics for the common cold and other inappropriate conditions • Use of antibiotics in animal feed • Failure to complete the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 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
