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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 Misuse includes: • Using outdated, weakened antibiotics • Using antibiotics for the common cold and other inappropriate conditions • Use of antibiotics in animal feed • Failure to complete the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 • Bacterial resistance Paenibacillus 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 Zmapp ZMapp is an experimental drug that combines three “humanized” monoclonal antibodies The new study explains why ZMapp could have been effective. Using an imaging technique called electron microscopy, researchers found that two of the ZMapp antibodies bind near the base of virus, appearing to prevent the virus from entering cells. A third antibody binds near the top of the virus, possibly acting as a beacon to call the body’s immune system to the site of infection. Phage Therapy Phage Therapy Phage Therapy
