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Chapter 20: Antimicrobial Drugs

Chapter 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: Substance produced by a microbe that, in small amounts, inhibits another microbe.

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Chapter 20: Antimicrobial Drugs

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  1. Chapter 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

  3. Antibiotic: Substance produced by a microbe that, in small amounts, inhibits another microbe Table 20.1

  4. www.textbookofbacteriology.net

  5. 1928 – Fleming discovered penicillin, produced by Penicillium (mold) • First clinical trials in early 1940s Figure 20.1

  6. Broad-spectrum antibiotics: those that affect a broad range of gram-positive and/or gram-negative bacteria Table 20.2

  7. Antimicrobial Drugs:Selective Toxicity • Selective toxicity: property of a drug that allows it to kill microbes without damaging the host cells • Takes advantage of differences in cell structure and metabolism between the microbe and host cells • Antibacterials: target prokaryotic structures • Penicillin prevents proper synthesis of peptidoglycan

  8. The Action of Antimicrobial Drugs • Bactericidal: causes death of bacteria • Bacteriostatic: prevents growth of bacteria

  9. Targets of Antimicrobial Drugs Figure 20.2

  10. Targets of Antimicrobial Drugs:Cell wall synthesis • Penicillin: weakens bacterial cell walls by inhibiting the crosslinking of peptidoglycan • Peptidoglycan is found only in bacterial cell walls • Bactericidal (must be actively growing)

  11. Targets of Antimicrobial Drugs:Cell Wall Synthesis Penicillins • Natural penicillins • Isolated from Penicillium mold • Narrow spectrum of activity • Susceptibility to penicillinases (or β–lactamases) • Semisynthetic penicillins • Chemically add new side chains to nucleus in attempt to • reduce susceptibility to penicillinase • extend their spectrum of activity

  12. Targets of Antimicrobial Drugs:Cell Wall Synthesis Penicillins • Semisynthetic penicillinase-resistant penicillins • Methicillin was the first • Resistant strains of staphylococci have become prevalent: MRSA (methicillin-resistant Staphylococcus aureus)

  13. Targets of Antimicrobial Drugs:Protein Synthesis • Exploit 70S ribosomes of prokaryotic cells • Eukaryotic (host) cells: 80S ribosomes • Host side effects due to mitochondrial toxicity (mitochondria: 70S) Figure 20.4

  14. Targets of Antimicrobial Drugs:Protein Synthesis • Tetracyclines • Broad spectrum of activity • Inhibit the association of tRNAs with the 70S ribosome • Prevent the addition of amino acids to the growing protein chain • Bacteriostatic http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/control/images/tetres.gif

  15. Other Targets of Antimicrobial Drugs • Plasma membranes • Drugs increase membrane permeability • Nucleic acid synthesis • May affect mammalian nucleic acid synthesis as well • Essential metabolite synthesis • Competitive inhibitors that prevent production of metabolites that are essential for growth/survival of the microbe

  16. Testing effectiveness of antibiotics on bacteria:Disk-Diffusion Test • Zone of inhibition diameter reflects susceptibility of test organism to antibiotic drug Figure 20.17

  17. Effects of Combinations of Drugs • Antagonism: the effect of two drugs together is less than the effect of either alone • Synergism: the effect of two drugs together is greater than the effect of either alone • i.e. Polymyxin (membrane-disrupting drug) makes it easier for streptomycin to enter the cell

  18. Effects of Combinations of Drugs Figure 20.22

  19. Antibiotic Resistance • Cellular mechanisms of antibiotic resistance: 1. Prevention of penetration of drug into cell 2. Alteration of drug's target site (Mutation) 3. Enzymatic destruction of drug 4. Rapid ejection of the drug (Efflux) • Resistance genes are often on plasmids that can be transferred between bacteria • 1968: 12,500 Guatemalans died of Shigella diarrhea • This strain contained a plasmid with resistance to four antibiotics http://www.fda.gov/cvm/antiresistvideo.htm

  20. Emergence of Antibiotic-resistant mutant bacteria • Antibiotic-resistant bacteria replacing the sensitive population • Every time an antibiotic is used, sensitive bacteria are killed, and resistant bacteria may survive and continue to grow (repopulate) • Presence of the antibiotic provides selective pressure • Selecting for antibiotic-resistant bacteria • Survival of the fittest Figure 20.20

  21. Infection Antibiotic Administration Inappropriate dose/duration Appropriate dose/duration Evolution of the surviving bacterial population -SELECTIVE PRESSURE -Sensitive cells die -Resistant cells survive, grow Extinction of the whole bacterial population -Sensitive cells die -Resistant cells die

  22. MRSA • About half of S. aureus infections in US are resistant to penicillin, methicillin, tetracycline, and erythromycin • Methicillin-resistant Staphylococcus aureus • Frequently used to describe S. aureus strains resistant to all penicillins • “Quite common” in hospitals • Current treatment for MRSA is vancomycin, the last weapon in the arsenal • VRSA was reported in 1997, and is (slowly) on the rise • As more antibiotics are discovered/synthesized, bacteria continue to adapt by developing and sharing antibiotic resistance

  23. MRSA infections: small red bumps  deep, painful abscesses http://www.mayoclinic.com/images/image_popup/ans7_staph_skin.jpg

  24. Antibiotic Resistance • One of the world’s most pressing health problems • Misuse of antibiotics selects for resistant mutants Misuse includes: • Using outdated, weakened antibiotics • Using someone else's leftover prescription • Failure to complete the prescribed regimen • Using antibiotics for the common cold and other inappropriate conditions • Use of antibiotics in animal feed Each of these applies selective pressure on a microbial population, favoring resistant cells.

  25. Acquisition of fluoroquinolone (FQ)-resistant Campylobacter from poultry. • FQ approved for use in poultry in 1995 • FQ use discontinued in 2001 www.cdc.gov/ncidod/EID/vol10no6/04-0403-G.htm

  26. Strategies to Reduce Emergence of Antibiotic-resistant bacteria • Prescription of antibiotics only when it will likely benefit the patient • Use an agent with narrow spectrum of activity when possible • Use antibiotics at the proper dose and duration

  27. http://www.nearingzero.net/screen_res/nz149.jpg

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