antimicrobial agents课件

Antimicrobial Agents,Mechanisms of Action and Spectra of Activity,OBJECTIVES,Describe major classes of antimicrobials and their mechanisms of action Know the spectra of activity of commonly used antibiotics Understand the mechanisms of resistance to antibiotics Know the principle and rationale behind antibiotic susceptibility testing,Overview of Antibiotics as Therapeutic Agents,Selective Inhibition/Toxicity Due to the differences in structure and metabolic pathways Harm microorganisms, not the host Four major sites: Cell wall Ribosomes DNA Cell membrane,Spectrum of Activity,Broad Spectrum Antibiotics: Effective against many types Example: Tetracycline Narrow Spectrum Antibiotics: Effective against very few types Example: Penicillin,Bactericidal v. Bacteriostatic,Bactericidal: Kill bacteria Used when the host defense mechanisms are impaired Required in endocarditis, kidney infection,Bacteriostatic: Inhibit bacteria Used when the host defense mechanisms are intact Used in many infectious diseases,MECHANISMS OF ACTION OF MAJOR GROUPS OF ANTIBIOTICS,STRUCTURE OF -LACTAM ANTIBIOTICS,PENICILLIN HOME,“Penicillin Home”,Looks like a house with a new room added to the side Think of the R-group as of a funky antenna Changing “antennae” and or finishing the “basement” will create better “homes” (penicillins),Penicillin Home Improvement Project,Adding a new antenna creates broad spectrum penicillins Example: Ampicillin Adding additional antennae and finishing the basement creates cephalosporins Example: 1st, 2nd, 3rd, & 4th generation cephalosporins,SPECTRUM OF ACTIVITY OF CEPHALOSPORINS,MECHANISM OF ACTION OF -LACTAM ANTIBIOTICS,-lactam antibiotics are ineffective against protoplasts and spheroplasts: A. TRUE B. FALSE,MECHANISMS OF ACTION OF ANTIRIBOSOMAL ANTIBIOTICS,Inhibition of Protein Synthesis,Anti-ribosomal antibiotics impair ribosomes by binding to either 50S or 30S ribosomal subunits Ribosomes are essential for translation of mRNA into proteins No translation No protein synthesis No protein synthesis No growth,Ribosome Home Plate,Baseball player slides into home The ball is fielded by the catcher who makes a CLEan TAG The word CLEean lies over the base: these inhibit 50S The word TAG lies beneath the base: these inhibit 30S,How are these drugs administered?,MECHANISM OF ACTION OF SULFONAMIDES AND TRIMETHOPRIM,Mechanisms of Resistance,Genetic Mechanisms Non-Genetic Mechanisms,Genetic Mechanisms,Chromosome-mediated Due to spontaneous mutation: in the target molecule in the drug uptake system Plasmid-mediated Common in Gram-negative rods Transferred via conjugation Multidrug resistance Transposon-mediated,Non-Genetic Mechanism,Inaccessibility to drugs (e.g., abscess, TB lesion) Stationary phase (insusceptible to inhibitors of cell wall synthesis) Protoplasts and spheroplasts (insusceptible to inhibitors of cell wall synthesis),The End Result of Genetically Conferred Resistance,Production of drug-inactivating enzymes Modification of target structures Alteration of membrane permeability,Resistance to Beta-Lactams,Gram + -lactamase (Penicillinase) Alteration of the transpeptidase enzyme,Gram - -Lactamase (Penicillinase) Alteration of porins,How can we test for susceptibility/resistance?,Antibiotic Susceptibility Testing,Dilution Method Disc Diffusion Method E-test High-Tech Methods,Dilution Method,Prepare two fold antibiotic dilutions Add 1/2 a million bacterial cells per tube Incubate overnight Check for turbidity Establish the MIC: The lowest concentration of the drug that prevented the bacterial growth (no turbidity),Disc Diffusion Method,Seed agar plates with bacteria in question Place antibiotic-discs over the seeded plate Incubate overnight Measure the inhibition zones Relate the results to the zones given in the interpretive chart There is an inverse relationship between the MICs and zone diameters,Therapeutic