Chapter 20-Antimicrobial Agents _______________:The use of drugs to treat a disease (not necessarily infectious) Antimicrobial drugs: Interfere with the growth of microbes within a host Antibiotic: Substance produced by a microbe that, in small amounts, ____________ another microbe Selective toxicity: A drug that kills harmful microbes without damaging the host

DISCOVERY and PURIFICATION of PENICILLIN 1928 – ___________ discovered penicillin, produced by Penicillium – Howard Florey and Ernst Chain performed first clinical trials of penicillin. Figure 20.1 Naturally occurring antimicrobials Metabolic products of bacteria and fungi _________: Streptomyces sp., Bacillus sp. _________: Penicillium sp., Cephalosporium sp.

THE ACTION OF ANTIMICROBIAL DRUGS Broad-spectrum Affect wide range of G+ and G- bacteria Disadvantage is disruption of ___________ Ex. Tetracycline Narrow-spectrum Affect small, __________ range of bacteria Gram positive only or gram negative only Ex. Penicillin G affects G+ but not G- bacteria

TYPES OF ANTIMICROBIAL ACTION Drugs may kill or inhibit bacterial growth 1._________________________ the growth of microorganisms Bacteriostatic drugs rely on host immunity to eliminate pathogen 2._________________________ microorganisms Bacteriocidal drugs are useful in situations when host defenses cannot be relied upon to control pathogen

____________ REACTIONS Allergies to penicillin Allergies often life threatening TOXIC EFFECTS Ex.: Aplastic anemia Body cannot make RBC or WBC SUPPRESSION of _______________ Antibiotic associated colitis Toxic organisms given opportunity to establish themselves ANTIMICROBIAL ________________ Microorganisms have innate or adaptive resistance to antibiotics ADVERSE EFFECTS OF ANTIMICROBIAL DRUGS

MAJOR ACTION MODES OF ANTI_______________ DRUGS

ANTI_____________ ANTIBIOTICS MODE of ACTION: Interference with essential processes of Mycobacterium tuberculosis 1. _________ (NIH) – inhibits synthesis of _______ acid 2. Ethambutol – inhibits incorporation of mycolic acid into the cell wall MODE of ACTION: Blocks _______________ 1. Rifampin

AMANTADINE and RIMANTADINE Mode of action: block the ______________ of influenza virus after it enters cell Reduces severity and duration of disease ZIDOVUDINE ____ and _____________ Mode of action: blocks nucleic acid synthesis ANTI-___________ DRUGS

Mode of action: Inhibition of ergosterol synthesis Amphotericin B Produced by Streptomyces species Treatment of ____________ fungal diseases Toxic to kidneys ___________________ Treatment of athlete’s foot and vaginal yeast infections Ketoconazole Less toxic than miconazole Topical application for cutaneous mycoses ANTI_______________ DRUGS Figure 20.15

Chloroquine Inhibits DNA synthesis Plasmodium species - __________ Metronidazole Damages DNA ___________ sp., Trichomonas sp. ANTI-____________ DRUGS

Niclosamide Prevents ATP generation _______________ Praziquantel Alters _________ permeability Flatworms Mebendazole Interferes with ________________________ Effective against tapeworms and roundworms Used in livestock industry ANTI-________________ DRUGS

KIRBY BAUER ANTIMICROBIAL SUSCEPTIBILITY TESTING: Figure 20.17

FOUR MAIN MECHANISMS of ANTIBIOTIC __________________________ Resistance genes are often on plasmids or transposons that can be transferred between bacteria.

Misuse of antibiotics selects for resistance Misuse includes: Using ___________________ antibiotics Using antibiotics for the common cold and other _________________ conditions Use of antibiotics in ________________ Failure to complete the prescribed regimen Using someone else's leftover prescription ANTIBIOTIC ______________

Staphylococcus aureus Common cause of __________________ infections Becoming increasingly resistant In past 50 years most strains acquired resistance to penicillin Due to acquisition of ____________ genes Until recently most infections could be treated with methicillin (penicillinase resistant penicillin) Many strains have become resistant MRSA  methicillin resistant Staphylococcus aureus MRSA strains are becoming resistant to vancomycin ANTIMICROBIAL RESISTANCE