Antimicrobial Chemotherapy

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Antimicrobial Chemotherapy

• WT 2006
• Bad Bugs An Introduction to Infectious Disease

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Selective Toxicity

• Want to kill bacteria not the host.

http//www.medem.com/MEDEM/images/jamaarchives/JAM
A_InfectiousDisease_Antibiotics_Lev20_Antibiotics_
JPP_01.gif
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Prokaryotes vs. Eukaryotes
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Bacterial Targets
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Cell Wall Inhibitors

• Generally more effective against Gram organisms.

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b-lactams
Pencillins
Cephalosporins
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Problems with b-lactam drugs

• Susceptible to degradative enzymes called
  b-lactamases or penicillinases.
• Sensitive to stomach acid.
• Cant cross outer membrane of G- organisms.
• Allergic reactions.

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Variations of Penicillin
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Vancomycin

• last resort antibiotic
• VRSA (vancomycin resistant Staphylococcus aureus)
• VISA (vancomycin intermediate Staphylococcus
  aureus)
• VRE (vancomycin resistant Enterococcus)

http//en.wikipedia.org/wiki/Vancomycin
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Bacitracin

• Topical antibiotic
• Nephrotoxin (toxic to kidneys)

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Cell Membrane Disruptor

• Polymyxin
• Makes membrane more permeable.
• Also found in Neosporin .
• Toxic to kidneys and to central nervous system.
• Only used topically.
• Highly effective against Pseudomonas.

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Protein Synthesis Inhibitors
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Aminoglycosides

• Examples
• Kanamycin
• Streptomycin
• Neomycin (in Neosporin)
• Broad spectrum
• Bactericidal

Kanamycin
http//www.genome.ad.jp/kegg/catalog/cpd_antibio1.
html
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Tetracyclines

• Examples
• Tetracycline
• Doxycycline
• Bacteriostatic
• Broad spectrum
• Side effects
• Discoloration of teeth in children
• Sensitivity to sunlight
• Gastrointestinal upset

http//www.sp.uconn.edu/terry/images/micro/tetrac
ycline.gif
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Macrolides

• Examples
• Erythromycin
• Azithromycin
• Bacteriostatic
• Effective against G
• Side effects
• Gastrointestinal upset
• Allergic reaction

http//nsm1.utdallas.edu/bio/gonzalez/lecture/micr
o/images/B4d.jpg
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Chloramphenicol

• Broad spectrum
• Bacteriostatic
• Side effect
• Aplastic anemia (irreversible loss of RBC stem
  cells)

http//www.itmonline.org/image/bees1.jpg
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Lincoamides (Lincomycins)

• Examples
• Lincomycin
• Clindamycin
• Broad spectrum
• Side effect
• Antibiotic-associated colitis due to Clostriudium
  difficile

http//www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu
8/images/antibiotics/lincomycin.gif
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Oxazolidinones

• Example
• Linezolid
• Effective against G
• Newest class of antibiotics so very little
  resistance has been observed.

http//www.mediscover.net/Files/structure2.gif
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Nucleic Acid Synthesis Inhibitors

• Selectively inhibit bacterial DNA or RNA
  synthesis.

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Quinolones/Fluoroquinolones

• Examples
• Ciprofloxacin
• Nalidixic acid
• Norfloxacin
• Inhibit DNA gyrase
• Bactericidal
• Broad spectrum
• Often used to treat UTIs

ciprofloxacin
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Rifamycins

• Example
• rifampin
• Block RNA polymerase
• Bactericidal
• Broad spectrum
• Primarily used to treat tuberculosis and leprosy.

http//www.itg.be/itg/DistanceLearning/LectureNote
sVandenEndenE/imagehtml/images/prevs/CD_1063_009c.
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Metabolic Inhibitors

• Sulfonamides (sulfa drugs)
• Broad spectrum
• Trimethoprim
• Used together, these drugs have synergistic
  effect.
• Commonly used to treat UTI.

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Drugs to Treat TB
Isoniazid

• Isoniazid
• Ethambutol
• Inhibit synthesis of mycobacterial cell wall
  components.

http//www.taacf.org/images/Isoniazid-2D.jpg
Ethambutol
http//www.medicinescomplete.com/mc/clarke/current
/images/clk0652c001.gif
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Be Responsible