抗生素英文-Antimicrobial-Agents.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,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,MECHANISMS OF ACTION OF MAJOR GROUPS OF ANTIBIOTICS,STRUCTURE OF,-LACTAM ANTIBIOTICS,PENICILLIN HOME,MECHANISM OF ACTION OF,-LACTAM ANTIBIOTICS,-lactam,antibiotics are ineffective against protoplasts and spheroplasts:,A.TRUEB.FALSE,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,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 Index=,Max.Safely Achievable Level,MIC,Take Home Message,Antibiotic Targets,Bactericidal v.Bacteriostatic Drugs,Spectrum of Activity,Major Groups of Drugs,Mechanisms of Resistance,Susceptibility Tests,