抗生素耐药的机理（英文）.ppt

Antibiotics Part 1 Dr P Gayo Munthali Consultant Microbiologist UHCW Honorary Associate Clinical Professor University of Warwick Objectives By the end of this lecture you should be able to: Explain the mode of action of beta lactams, aminoglycosides, fluoroquinolones, macrolides, tetracyclines and glycopeptides Mention the major side effects of the antibiotic groups in (1) Appreciate different types of resistance and in simple terms, explain the mechanisms of resistance to beta lactams Explain some limitations in the use of antibiotics in (1) Understand the general spectrum of activity of antibiotics in (1) Antibiotics, Point of Action Important mechanisms of resistance to antibiotics ?-Lactams Penicillins and Cephalosporins Carbapenems and Others Mobactams Mechanisms of Action Inhibit bacterial enzymes involved in cell wall synthesis Penicillin binding proteins (PBPs) essential for peptidoglycan synthesis Trigger membrane associated autolytic enzymes that destroy cell wall Inhibit bacterial endopeptidase and glycosidase enzymes which are involved in cell wall growth Time dependent activity Spectrum of Activity Very wide Gram positive and negative bacteria Anaerobes Spectrum of activity depends on the agent and/or its group Aztreonam only active against gram negatives Pharmacokinetics Absorption PO forms have variable absorption Food can delay rate and extent of absorption Distribution Widely to tissues fluids CSF penetration: IV – limited unless inflamed meninges IV 3rd 4th generation cephalosporins, meropenem, Aztreonam – penetrate well Metabolism Excretion Primarily renal elimination Some have a proportion of drug eliminated via the liver ALL ?-lactams have short elimination half-lives Adverse Effects Penicillin hypersensitivity – 0.4% to 10 % Mild: rash Severe: anaphylaxis death There is cross-reactivity among all Penicillins Penicillins and cephalosporins ~5-15% Penicillins and carbapenems~1% (may be higher) Desensitization is possible