1. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY BY: DR ALPANA VERMA Head, Department of Microbiology and Parasitology
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21. Measurement of antimicrobial activity Minimal inhibitory concentration: the lowest concentration of an antimicrobial compound that prevents growth of a microbe in vitro 0.05 0.1 0.2 0.4 0.8 1.6 3.2 6.3 12.5 25 50 µg/ml Add growth medium Add dilutions of test compound Inoculate & incubate cultures No drug: control MIC
22. Inoculate small samples on drug-free plates Minimum cidal concentration: the lowest concentration of an antimicrobial compound that kills a microbe in vitro Incubate plates Minimal inhibitory concentration: the lowest concentration of a antimicrobial compound that prevents growth of a microbe in vitro 0.05 0.1 0.2 0.4 0.8 1.6 3.2 6.3 12.5 25 50
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34. Mechanisms of antibacterial action DNA mRNA ribosomes THF DHF pABA 50S 30S 50S 30S 50S 30S folate synthesis sulphonamides trimethoprim DNA topoisomerases quinolones, novobiocin RNA polymerase rifampicin cell membrane polymyxins protein synthesis (30S) tetracyclines aminoglycosides fusidic acid and others protein synthesis (50S) macrolides lincosamides chloramphenicol oxazolidinones cell wall -lactams vancomycin bacitracin
46. Action of β -lactamase on penicillin. A number of bacteria, especially staphylococci, possess the enzyme β -lactamase (penicillinase), which inactivates penicillin by cleavage of the β -lactam ring at the point marked by the arrow
81. Mechanisms of antimicrobial resistance 1. inactivate antimicrobial molecule e.g. -lactamases: produced by many G+ and G– bacteria genes for -lactamases often carried on plasmids, so easily spread between bacteria 2. alter antimicrobial target specific mutations in genes encoding target proteins can cause resistance without loss of target’s function 3. prevent access of antimicrobial to target e.g. reductions in permeability to drug (porins) drug efflux mechanisms — multi-drug resistance pumps 4. overexpress antimicrobial target 5. use alternative pathways to the one including the target
82. Spread of antimicrobial resistance transposon mobile genetic element carrying a drug resistance gene expressed from its own promoter: hops from chromosome to plasmid drug resistance plasmids can carry more than one drug resistance-encoding gene easily transferred between organisms integrons groups of drug resistance genes in a large array, under control of a single promoter responsible for rapid spread in Gram-positive bacteria