CEPHALOSPORINS

∑ Fungi of Cephalosporium sp yielded several antibiotics that resembled penicillins but were resistant to beta-lactamase and were active against both gram-positive and gram-negative bacteria

∑ Both penicillins & cephalosporins have a beta-lactam ring which confers on them a similar mode of action ie a Beta-lactam antibiotic

∑ Are primarily bactericidal in action; act by inhibiting cell wall synthesis, like the penicillins, with resulting defective cell walls so that the protoplasts are osmotically unstable

∑ More effective against young, rapidly dividing organisms than against mature, resting cells that are not in the process of cell-wall formation

∑ In general, gram negative bacteria are less sensitive because they contain less mucopeptide in the cell wall

∑ Are broad spectrum antibiotics and demonstrate activity against most gram positive organisms and some gram negative organisms

∑ Bacterial resistance may be natural or acquired: some bacteria are resistant because their ell walls are impermeable to cephaloporins or their metabolic pathways are not inhibited; other bacteria are resistant due to production of of beta-lactamases (cephalosporinases)

∑ Although cephalosporins are highly resistant to the penicillinase-resistant penicillins beta-lactamases, cross resistance between penicillinase-resistant penicillins and cephalosporins occurs

∑ Should be avoided in patients who have had a anaphylactic reaction to penicillin

∑ Should be administered with caution in presence of renal failure

1st Generation Cephalopsporin [Cephazolin; Cephalothin]

∑ Narrow spectrum

∑ Lack stability to gram-negative beta-lactamases

∑ Inactive against pseudomonas but good against most gram-positive

∑ Intravenous injected penetrates most tissues well & is the drug of choice for surgical prophylaxis [particularly during insertion of prothetic devices]

∑ Relatively non toxic

∑ May be given to patients who exibit a mild reaction to penicillin

2nd Generation Cephalopsporin [Cephamandole; Cefoxitin; Cefuroxime]

∑ Intermediate spectrum

∑ More active against gram-negative and pseudomonas than 1st generation

∑ Less active against gram-positive bacteria than 1st generation

∑ Lack activity against enterococcus

∑ Cefoxitin is not susceptible to beta-lactamases produced by gram-negative organisms

3rdGeneration Cephalopsporin [Cefotaxime; Ceftazidime]

∑ Broad spectrum

∑ Expanded gram-negative coverage

∑ Able to reach CNS

∑ Relatively free from significant toxicity

∑ Lack activity against enterococcus

∑ Increased resistance to beta-lactamases produced by gram-negative organisms

∑ Long half life

∑ Expensive