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ANTIMICROBIAL DRUGS ANTIBIOTICS Chemical substances produced by certain microorganisms either inhibit the growth of other microorganisms or kill

ll them Synthetic antibacterial agents

RESISTANCE Refers to bacterial growth which is not reduced by an antimicrobial agent General Mechanisms for Resistance: Failure of antibiotic to permeate the microorganism Decreased affinity of the drug for its target binding site Inactivation of the drug by microbial enzymes CROSS-RESISTANCE Refers to resistance of organisms to drugs of similar structure and mechanisms of action SPECTRUM Range of antimicrobial activity which a certain agent covers BACTERIOSTATIC BACTERICIDAL

SELECTION OF ANTIMICROBIAL AGENTS Identification of the organism and sensitivity of it to a particular agent The safety of the agent and toxic effects it may have on a particular patient The site of infection may limit the use or determine how an agent should be administered BACTERIAL CELL WALLS Vital for the normal growth and development of bacteria Peptidoglycan (murein)- essential component of the cell wall CELL WALL Rigid outer layer that is unique to bacteria It surrounds the cytoplasmic cell membrane Maintains the shape of the cell and protects bacteria Possess a high internal osmotic pressure (hyperosmolar)

Contains a cross-linked polymer of glycan known as peptidoglycan (murein, mucopeptide) CELL WALL SYNTHESIS INHIBITORS AND B-LACTAMASE INHIBITORS

CELL WALL SYNTHESIS INHIBITORS Bactericidal Kills bacteria by selectively interfering with either the synthesis or repair of the cell wall B-LACTAMASE INHIBITORS Are usually used in combination with a variety of penicillins to extend their spectrum and protect them from B-lactamases Alone, they are ineffective bacterial agents PENICILLINS Are among the most important B-lactam antibiotics

Mechanism of Resistance 1. Production of enzymes (e.g. B-lactamases) by certain organisms that break the beta-lactam ring of penicillin 2. Removal or alteration of specific receptors to which the antimicrobials bind 3. Decreased permeability to the drug preventing it from reaching its target binding receptors 4. Inhibition of cell wall autolytic enzymes 5. Organisms that lack a cell wall or that are metabolically inactive are not susceptible to penicillins or other cell walls inhibitors Penicillin Binding Proteins (PBPs) Are bacterial enzymes located on the bacterial cytoplasmic membrane Involved in the synthesis of the cell wall and maintenance of bacterial morphology Transpeptidases Bacterial enzymes responsible for the final step in cell wall synthesis by cross-linking linear peptidoglycan chains B-lactamases Family of bacterial enzymes which hydrolyze the cyclic amide bond of the B-lactam ring