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Step-wise resistance due to low-affinity PBPs - CISMED分步阻力是由于低亲和力青霉素结合蛋白- cismed
Antibiotic Resistance Mechanisms of Resistance Antibiotics exert selective pressure that favors emergence of resistant organisms Bacteria employ several biochemical strategies to become resistant Genetic Basis of Resistance Spontaneous mutations in endogenous genes Structural genes: expanded spectrum of enzymatic activity, target site modification, transport defect Regulatory genes: increased expression Acquisition of exogenous sequences Usually genes that encode inactivating enzymes or modified targets, regulatory genes Mechanisms of DNA transfer: conjugation (cell-cell contact); transformation (uptake of DNA in solution); transduction (transfer of DNA in bacteriophages) Expression of resistance genes Reversible induction/repression systems can affect resistance phenotypes Spread of Resistance Genes Major Classes of Antibiotics Antibiotic Susceptibility Tests Minimal inhibitory concentration (MIC) Reference method. Add standard inoculum to dilutions of antibiotic. Incubate overnight. MIC is lowest concentration that inhibits growth (can also be performed by agar dilution). Interpretation (S or R) is based on achievable drug levels Antibiotic Susceptibility Tests Kirby-Bauer agar disk diffusion Paper disk containing antibiotic is placed on lawn of bacteria, then incubated overnight. Diameter of zone of inhibition is inversely related to MIC (used to establish interpretive breakpoints). Standardized for commonly isolated, rapidly growing organisms. Antibiotic Susceptibility Tests E-test Strips containing a gradient of antibiotic are placed on lawn of bacteria and incubated overnight. MIC is determined at point where zone of inhibition intersects scale on strip. Combines ease of KB with an MIC method. Particularly useful for S. pneumoniae. b-lactam Antibiotics Structure of Peptidoglycan Penicillin-Binding Proteins (PBPs) Membrane bound enzymes Catalyze final steps of peptidoglycan synthesis (transglycosylation and transpeptidation) Multiple essential PBPs (4-5) -
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