Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings PowerPoint ® Lecture Slide Presentation prepared by Christine L. Case Microbiology B.E Pruitt & Jane J. Stein AN INTRODUCTION EIGHTH EDITION TORTORA FUNKE CASE Ch. 10 Antimicrobial Drugs

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 1928 – Fleming discovered penicillin, produced by Penicillium – Howard Florey and Ernst Chain performed first clinical trials of penicillin. Figure 20.1

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Table 20.1

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Table 20.2

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Action of Antimicrobial Drugs Broad-spectrum Narow-spectrum Superinfection Bactericidal Bacteriostatic

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Action of Antimicrobial Drugs Figure

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Action of Antimicrobial Drugs Figure

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penicillin Natural penicillins Semisynthetic penicillins Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penicillins Figure 20.6

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Penicillin Penicilinase-resistant penicillins Extended-spectrum penicillins Penicillins +  -lactamase inhibitors Carbapenems Monobactam Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Figure 20.8

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Cephalosporins 2 nd, 3 rd, and 4 th generations more effective against gram-negatives Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Figure 20.9

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Polypeptide antibiotics Bacitracin Topical application Against gram-positives Vancomycin Glycopeptide Important "last line" against antibiotic resistant S. aureus Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antimycobacterium antibiotics Isoniazid (INH) Inhibits mycolic acid synthesis Ethambutol Inhibits incorporation of mycolic acid Carbapenems Imipenen has widest spectrum of activity of ß-lactam drugs Monobactams Aztreonam has excellen activity against gr-ve but not gr+ve or anaerobes Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Chloramphenicol Broad spectrum Binds 50S subunit, inhibits peptide bond formation Aminoglycosides Streptomycin, neomycin, gentamycin Broad spectrum Changes shape of 30S subunit Antibacterial Antibiotics Inhibitors of Protein Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Tetracyclines Broad spectrum Interferes with tRNA attachment Macrolides (azithromycin, clarithromycin) Gram-positives Binds 50S, prevents translocation Erythromycin Gram-positives Binds 50S, prevents translocation Antibacterial Antibiotics Inhibitors of Protein Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Streptogramins Gram-positives Binds 50S subunit, inhibits translation Synercid Gram-positives Binds 50S subunit, inhibits translation Linezolid Gram-positives Binds 50S subunit, prevents formation of 70S ribosome Antibacterial Antibiotics Inhibitors of Protein Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Polymyxin B Topical Combined with bacitracin and neomycin in over- the-counter preparation Antibacterial Antibiotics Injury to the Plasma Membrane

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Rifamycin Inhibits RNA synthesis Antituberculosis Quinolones and fluoroquinolones Ciprofloxacin Inhibits DNA gyrase Urinary tract infections Damage growing bones and cartilages Antibacterial Antibiotics Inhibitors of Nucleic Acid Synthesis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antibacterial Antibiotics Inhibitors of Nucleic Acid Synthesis Inhibition of precursor synthesis Sulfonamides Trimethoprim Inhibition of DNA synthesis Quinolones Flucytosine Inhibition of mRNA synthesis Rifampin

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Sulfonamides (Sulfa drugs) Inhibit folic acid synthesis Broad spectrum Antibacterial Antibiotics Competitive Inhibitors Figure 5.7

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure P-aminobenzoic acid

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Alternation of bacterial cell membranes Polymyxins (E) Mainly active against gr-ve “P. aeruginosa” Alteration of fungal cell membranes Amphotericin B “high affinity for ergosterol” (polyene) Nystatin “topically, Candida” Azoles “act by inhibiting ergosterol synthesis” „ e.g. Fluconazole, ketoconazole, itraconazole, clotrimazole and miconazole“ Alternation of cell membrane function

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Used to prevent diseases Prior to surgery Immunocompromised patients Against certain pathogens Chemoprophylaxis

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Live, nonpathogenic bacteria Providing colonization resistance Enhancing the immune system against pathogen Reduce the inflammation response against the pathogen e.g. Lactobacillus rahmnosus Probiotics

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Polyenes Amphotericin B Azoles Miconazole Triazoles Allylamines Inhibition of Nucleic Acids Flucytocine Cytosine analog interferes with RNA synthesis Pentamidine isethionate Anti-Pneumocystis; may bind DNA Antifungal Drugs Inhibition of Ergosterol Synthesis Figure 20.15

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Griseofulvin Used for superficial mycoses Tolnaftate Used for athlete's foot; action unknown Antifungal Drugs Inhibition of Microtubules (Mitosis)

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16a

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antiviral Drugs Nucleoside and Nucleotide Analogs Figure 20.16b, c

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Protease inhibitors Indinavir HIV Inhibit attachment Zanamivir Influenza Inhibit uncoating Amantadine Influenza Interferons prevent spread of viruses to new cells Viral Antiviral Drugs Enzyme Inhibitors

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Antihelminthic Drugs Niclosamide Prevents ATP generation Tapeworms Praziquantel Alters membrane permeability Flatworms Pyantel pamoate Neuromuscular block Intestinal roundworms

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Disk-Diffusion Test Figure 20.17

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings E Test Figure 20.18

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings MIC Minimal inhibitory concentration MBC Minimal bactericidal concentration Serum Bactericidal Activity ß-Lactamase Production Antibiotic Sensitivity Testing

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Broth Dilution Test Figure 20.19

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Overuse or 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 Antibiotic Resistance

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings 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. Indifference occurs when the effect of two drugs together is almost the same as the effect of either alone. Effects of Combinations of Drugs

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Effects of Combinations of Drugs Figure 20.22