antibiotics-11 - VI. Antimicrobial chemotherapy NOTE: I...

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16 VI. Antimicrobial chemotherapy NOTE: I expect you to understand the principles of antimicrobial therapy and the general characteristics of the major antibiotics listed below . A. Based on selective toxicity - toxic to bacteria, not bad for us 1. Selective toxicity based on differences in physiology between bacteria and us 2. Measured as therapeutic index = toxic dose/therapeutic dose (high is good) 3. Also consider allergenicity B. Bactericidal vs. bacteriostatic 1. bactericidal - kills bacteria (irreversible) 2. bacteriostatic - stops growth (reversible) 3. measured in lab as: a. Minimum Bactericidal Concentration (MBC) - lowest dose for complete killing b. Minimum Inhibitory Concentration (MIC) - lowest dose for stasis C. Pharmacologic absorption and distribution in body 1. oral vs. i.v. 2. penetration to relevant site (e.g., blood brain barrier or inside of host cells) 3. rate of excretion 4. rate of metabolism E. Broad spectrum vs. narrow spectrum 1. broad good for unknown bacterial agent with serious effects 2. narrow good for known bacterial agent F. Existing antibiotic resistance among the population G. combination therapies 1. synergistic 2. additive 3. antagonistic H. Other practical considerations for compliancy 1. cost 2. frequency and length of administration 3. for pediatrics - taste! I. Summary of key antimicrobials 1. peptidoglycan a. β -lactams inhibit transpeptidation (similar in structure to D-Ala-D-Ala) i. penicillins (methicillin, amoxicillin) ii. cephalosporins (in third generation) iii. carbapenems b. monobactams inhibit transpeptidation c. vancomycin inhibits transpeptidation (recognizes D-Ala-D-Ala, note difference with β -lactams) d. bacitracin transport of the subunits across membrane 2. Outer membrane - polymyxins (similar to cationic detergents)
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17 3. Protein synthesis - act at ribosome a. aminoglycosides: gentamicin, kanamycin, neomycin, streptomycin b. aminocyclitols: spectinomycin c. tetracycline d. chloramphenicol e. macrolides: erythromycin , azithromycin 4. DNA synthesis a. quinolones inhibit gyrase: nalidixic acid, ciprofloxacin b. metronidazole incorporated into DNA after metabolism in anaerobes 5. RNA synthesis - rifampin (rifampicin, rifamycin) and its derivatives 6. metabolic inhibitors - folic acid inhibitors a. sulfonamides - PABA analogs block dihydropteroate synthetase b. trimethoprim blocks dihydrofolate reductase 7. Inhibitors of antibiotic resistance function a. clavulanic acid inhibits β -lactamase b. used in conjunction with amoxicillin (
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antibiotics-11 - VI. Antimicrobial chemotherapy NOTE: I...

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