抗生素英文课件精品microbiologyprinciples and

Microbiology: Principles and Explorations Sixth Edition Chapter 13: Antimicrobial Therapy Copyright 2005 by John Wiley & Sons, Inc. Jacquelyn G. Black Antimicrobial Agents A special group of chemotherapeutic agents used to treat diseases caused by microbes Antibiosis: literally means “against life” Antibiotic: A chemical substance produced by microbes which has the capacity to inhibit or destroy the growth of bacteria/other microbes Synthetic/semi-synthetic drugs 1910: Paul Ehrlich used Salvarsan to treat syphilis 1935: Gerhard Domagk discovered prontosil, a red dye, inhibits growth of many gram-positive bacteria 1936: Ernest Fourneau discovered that the sulfanilamide portion contained antimicrobial activity The History of Chemotherapy Selective Toxicity The Spectrum of Activity Modes of Action Side Effects The Resistance of Microorganisms General Properties of Antimicrobial Agents The antimicrobial agent must harm the microbes without causing significant damage to the host Toxic dosage level: causes host damage Therapeutic dosage level: successfully eliminates the pathogenic organism if the level is maintained Selective Toxicity The range of different microbes against which an antimicrobial agent acts Broad spectrum: Agents effective against both gram-positive and gram- negative bacteria Narrow spectrum: Agents effective against a small number of microbes Spectrum of Activity Spectrum of Activity Inhibition of cell wall synthesis Disruption of cell-membrane function Inhibition of protein synthesis Inhibition of nucleic acid synthesis 5. Action as antimetabolites Modes of Action Modes of Action Inhibiting cell wall synthesis selectively damages bacterial and fungal cells Penicillin and cephalosporin contain a structure called a -lactam ring The -lactam ring attaches to the enzymes that cross-link peptidoglycans and prevent cell wall synthesis Inhibition of Cell Wall Synthesis Bacteria Before Exposure to Penicillin Bacteria After Exposure to Penicillin Certain polypeptide antibiotics, such as polymyxins Act as detergents and distort bacterial cell membranes Bind to phospholipids in the membrane Especially effective against gram-negative bacteria which have an outer membrane Disruption of Cell Membrane Function An example of selective toxicity Attack bacterial cells without significantly damaging animal cells Aminoglycoside antibiotics: Tetracycline, Erythromycin, streptomycin, chloramphenicol Bind to the bacterial 30S ribosomal subunit and interfere with the translation of mRNA Inhibition of Protein Synthesis Differences between the enzymes used by bacterial and animal cells to synthesize nucleic acids Antibiotics of the rifamycin family bind to a bacterial RNA polymerase and inhibit RNA synthesis Inhibition of Nucleic Acid Synthesis Substances that affect the utilization of metabolites and prevent metabolic reactions Function in two ways: Competitively inhibiting enzymes Erroneously incorporated into important molecules such as nucleic acids Action as Anti-metabolites Competitive Inhibition Nucleic Acid Base Analogs The side effects of antimicrobial agents fall into three general categories: Toxicity Allergy Disruption of normal microbiota Kinds of Side Effects Acquisition of Resistance 1.Microorganisms normally acquire antibiotic resistance by genetic changes: 2.Natural Selection 2.Chromosomal Mutation 3.Extrachromosomal Resistance 1.R Plasmids or R factors Method of Detecting Genetic Resistance Alteration of Targets Alteration of Membrane Permeability Development of Enzymes Alteration of an Enzyme 5. Alteration of a metabolic pathway Mechanisms of Resistance b-lactamase Effect on Penicillin This mechanism usually affects bacterial ribosomes The mutation alters the DNA such that the protein produced or target is modified Antimicrobial agents can no longer bind to the target Resistance to erythromycin, rifamycin, and anti- metabolites Alteration of Targets B-lactamase These enzymes are found in various bacteria They catalyze the breaking of the B- lactam ring in penicillins and some cephalosporins Enzyme Development First-Line, Second-Line Third-Line Drugs 1930s sulfonamides were found to cure the disease, gonorrhea Sulfonamide-resistant strains developed and penicillin was used as a cure Penicillin-resistant strains developed and spectinomycin was used Now there are spectinomycin-resistant strains of gonorrhea Effects of Premature Termination of Antibiotic Treatment Kirby-Bauer Method of Determining Microbial Sensitivities to Various Antibiotics Minimal Inhibitory Concentration (MIC) Microbial Susceptibility An Epsilometer (E) Test for Determining Antibiotic Sensitivity Inoculating Samples Into Individual Wells Containing Specific Chemical Agents Incubator Chamber Structures of Penicillin and Related Molecules Staining of Teeth by Tetracycline Red Man Syndrome Agents That Inhibit Protein Synthesis Agents That Inhibit Nucleic Acid Synthesis Agents That Inhibit Cell Wall Synthesis Agents That Interfere With Cell Membrane Function Antimetabolites and Other Agents Black Hairy Tongue: A Reaction to Metronidazole (Flagyl) Antifungal Agents Antihelminthic Agents Antiviral Agents Antiprotozoan Agents Disrupters of Cell Membranes Polymyxins (A, B, C, D, and E) Obtained from soil bacterium Bacillus polymyxa Usually applied topically, often with bacitracin, to treat skin infections caused by Pseudomonas Internally, can cause numbness in the extremities, serious kidney damage, and respiratory arrest Tetracyclines Obtained from species of Streptomyces Are bacteriostatic, readily absorbed from the digestive tract, and becom