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Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spre

Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spread?. First steps: chemotherapeutics drugs that killed the microbe but not the patient! Salvarsan (Ehrlich; arsenic; syphilis)

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Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spre

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  1. Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spread?

  2. First steps: chemotherapeutics drugs that killed the microbe but not the patient! Salvarsan (Ehrlich; arsenic; syphilis) Pronotsil (Domagk; sulfa drugs; streptococcus) Antibiotics: produced by microorganisms Fleming: penicillin Waksman: streptomycin More recently, compounds have been altered

  3. Features of antimicrobials (why do most come from soil microbes?) Selective toxicity Type of action bactericidal bacteriostatic Depends of stage of growth of microbe; sensi- tivity to immune mechanisms Spectrum- broad or narrow broad can be prescribed quickly but kill normal flora, too

  4. Metabolism; distribution; stability Must drug be injected? How long does drug persist in system? Can drug cross blood-brain barrier? Does patient have normal liver and kidney function?

  5. What are adverse effects? Hypersensitivity Toxic effects aminoglycosides; chloramphenicol Suppression of normal flora Efficacy Cost

  6. p. 511 How do these drugs work?

  7. Inhibitors of cell-wall synthesis Penicillins Cephalosporins (what types of organisms make them?) Enzyme inhibitors (-lactam rings) Prevent formation of peptidoglycan (vancomycin) Interfere with precursor transport (bacitracin) See table 21.2, pp. 513-514

  8. p. 515

  9. Inhibition of protein synthesis p. 516

  10. These are pretty toxic Aminoglycosides- kidney damage, deafness Neomycin can’t be taken internally Tetracyclines can discolor teeth in children Chloramphenicol- aplastic anemia Newer drugs are less toxic Tend to be broad spectrum (not always)

  11. Other targets nucleic acid synthesis (fluoroquinolones, rifamycins) metabolic pathways, etc. folic acid (humans lack this pathway, therefore these enzymes) trimethoprim, sulfanolamides cell membranes (polymixin B) specialty drugs- antituberculars slow growth; waxy coat; intracellular

  12. How do you know if a particular drug will be effective? Minimum inhibitory concentration (MIC) Minimum bactericidal concentration (MBC) (giving combinations is risky for toxicity, hypersensitivity, drug resistance)

  13. p. 519

  14. Kirby-Bauer is quicker and easier p. 519; tests have been modified

  15. It doesn’t take long for microbes to become drug-resistant! p. 521

  16. Mechanisms of drug resistance, p. 522 Mutation or gene transfer?

  17. p. 522 many resistance genes are on plasmids

  18. Important resistant organisms Vancomycin-resistant enterococci MRSA (methicillin-resistant S. aureus) Penicillin-resistant S. pneumoniae Multiple-drug-resistant M. tuberculosis

  19. How can we prevent the formation of drug- resistant microbes? Health workers: prescribe appropriately! Patients: take drugs as prescribed! Don’t take antibacterials for viral infections! Should antibacterials be easily available? Should we use them in animal feed?

  20. Not all infections are caused by bacteria. What are appropriate treatments for viruses fungi protozoans helminths

  21. Viruses are challenging because many have no unique target structure If immune system doesn’t control infection: Prevent viral replication Prevent viral polymerase activity Prevent assembly and release of new virions

  22. p. 525

  23. Fungal cells are similar in structure to animal cells: drugs toxic to fungi are generally toxic Exception: ergosterol (found in plasma membrane). Drugs are usually safe topically but not systemically

  24. Treating protozoan and helminthic diseases Inhibit cell division or metabolism Neurotoxins for helminths (see p. 529)

  25. New strategies New targets for antimicrobials? Interfere with resistance mechanisms? Enhance host defenses? New vaccine concepts?

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