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Ch 20

Ch 20. Antimicrobial Drugs. Antimicrobial Drugs. Chemotherapy: The use of drugs to treat a disease. Antimicrobial drugs: Interfere with the growth of microbes within a host. Antibiotic : Of biological origin. Produced by a microbe, inhibits other microbes.

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Ch 20

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  1. Ch 20 Antimicrobial Drugs

  2. Antimicrobial Drugs • Chemotherapy: The use of drugs to treat a disease. • Antimicrobial drugs: Interfere with the growth of microbes within a host. • Antibiotic: Of biological origin. Produced by a microbe, inhibits other microbes. • Chemotherapeutic agent: synthetic chemicals • Today distinction blurred  many newer "antibiotics" are biological products that are • chemically modified or • chemically synthesized

  3. Features of Antimicrobial Drugs • Selective toxicity: Drug kills pathogens without damaging the host. • Therapeutic index: ratio between toxic dose and therapeutic dose – or ratio of LD50 to ED50High therapeutic index  less toxic • Antimicrobial action – Bacteriostatic vs. bactericidal • Activity Spectrum – Broad-spectrum vs. narrow- spectrum • Tissue distribution, metabolism, and excretion – BBB; Unstable in acid; half-life duration

  4. The History of Chemotherapy • Paul Ehrlichand Sahachiro Hata developedSalvarsan (Arsphenamine) against syphilis in 1910: The concept of chemotherapy to treat microbial diseases was born. • Sulfa drugs (sulfanilamide) discovered in 1935  against gram + bacteria

  5. The History of Chemotherapy cont. 1928: Fleming discovered penicillin 1940: Howard Florey and Ernst Chain performed first clinical trials of penicillin. Fig 20.1

  6. The Sites of Activity in a Bacterial Cell for Various Antibiotics Compare to Fig 20.2

  7. Antibacterial AntibioticsInhibitors of Cell Wall Synthesis: Penicillin Natural and semisynthetic penicilins contain β-lactam ring Natural penicillins produced by Penicillium are effective against Gram + cocci and spirochetes Semisynthetic penicillins: made in laboratory by adding different side chains onto β-lactam ring  penicillinase resistant and broader spectrum of activity Penicillinase (β-lactamase): bacterial enzyme that destroys natural penicillins Penicillinase resistantpenicillins: methicilin replaced by oxacilin and nafcilin due to MRSA Extended-spectrum penicilins: Ampicilin, amoxicilin; new: carboxypenicilins and ureidopenicillins (also good against P. aeruginosa)

  8. Compare to Fig 20.8

  9. Cephalosporins Fungi of genus Cephalosporium  4 Generations of cephalosporins Chemical structure and mode of action resembles penicilins Advantages: More stable than penicilins to bacterial -lactamases, broader spectrum  used against penicillin-resistant strains. Incidence of cross-sensitivity with penicillin estimated at  5-16%

  10. Vancomycin • Glycopeptide from Streptomyces • Inhibition of cell wall synthesis • Used to kill MRSA • Emerging Vancomycin resistance: VRE and VRSA

  11. Antifungal Drugs • Polyenes, such as nystatin and amphotericin B, for systemic fungal infections. Combine with fungal plasma membrane sterols  fungicidal. Nephrotoxic • Griseofulvin from Penicillium. Systemic/oral. Interferes with eukaryotic cell division and is used primarily for superficial dermatophytoses.

  12. Antiviral Drugs Nucleoside analogs inhibit DNA synthesis • Acyclovir and newer derivatives: Selective inhibition of herpes virus replication. Acyclovir conversion to nucleotide analog only in virus infected cells  very little harm to uninfected cells! • AZT: reverse transcriptase inhibitor • Inhibitors of viral enzymes are used to treat influenza and HIV infection, e.g.: Protease inhibitors • -interferons inhibit spread of viruses to new cells Figure 20.16a

  13. Protease Inhibitors HIV protease cleaves viral polypeptide into functional proteins Protease inhibition  HIV cannot mature and noninfectious viruses are produced.

  14. Antiprotozoan and Antihelminthic Drugs • Chloroquine, quinacrine, diiodohydroxyquin, pentamidine, and metronidazole (Flagyl) are used to treat protozoan infections. • Antihelminthic drugs include mebendazole, praziquantel, and ivermectin.

  15. Antibiotic Assays to Guide Chemotherapy Two general methods for Susceptibility Testing: • Tube dilution method determines minimum inhibitory concentration (MIC) MIC = the lowest concentration of antibiotic sufficient to inhibit bacterial growth when tested in vitro. 2.Agar disk diffusion method determines susceptibility of an organism to a series of antibiotics. Kirby-Bauer test

  16. Drug Resistance Penicillin G resistance of S. aureus from 3% to > 90% Multidrug-resistant S. aureus = MRSA or “super-bug” Vancomycin-resistance  Multi drug resistant TB = MDR-TB Mechanisms of resistance: • Vertical evolution due to spontaneous mutation • Horizontal evolution due to gene transfer

  17. Read Microbiology In the NewsAntibiotics in Animal Feed Linked to Human Disease (p. 606) the end

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