头孢菌素类抗生素（英文PPT）Cephalosporin Antibiotics.ppt

Cephalosporin Antibiotics First discovered in 1945 from a Cephalosporium fungi Commercial drugs derived semi-synthetically From 7-aminocephalosporanic acid - produced by fermentation Similar to penicillins – 4 Generations Derivatives acylated at the 7-amino group Reasons for synthetic modification include: Increased acid stability Improved pharmacokinetics (oral absorption) Broaden antimicrobial spectrum Increased activity (decreased resistance due to destruction) Improved penetration Increased receptor affinity Decreased allergenicity Increased tolerance due to parenteral administration Cephalosporin Antibiotics Transition from first generation to third generation agents reflects Broadening of the Gram (-) organism spectrum Loss of efficacy against Gram (+) organisms Greater efficacy against resistant organisms (but increased cost) MOA: Inhibit cell wall synthesis ? osmotically induced cell lysis Usually bactericidal – a function of dosage, organism susceptibility, tissue concentrations, and growth rate Cross allergenicity with penicillins is 5-16% Drug interactions: Alcohol use may produced a disulfiram like reaction - NMTT Aminoglycoside nephrotoxicity can be increased Anticoagulant effects can be potentiated - NMTT Antacids can decrease plasma concentrations of oral agents Loop diuretic nephrotoxicity can be increased Monitor renal function since all are renally excreted Cefoperazone the exception Cephalosporin Antibiotics Classified by Generations - explosive advances First Generation Epitomized by cefazolin Good activity against Gram(+) Modest Gram(-) activity Second Generation Increased Gram(-) activity Some active against baccillus fragilis (highly resistant anaerobe) Third Generation - cost vs. efficacy “Broad” spectrum with high penicillinase resistance Greater Gram (-) spectrum Less active than G1 against most Gram(+) More active than G1 against enterobacter Fourth Generation - Cefepime Extended range of activity compared to G3 – More Gram (+) Increas