Cefoxitine has got no activity against anaerobes Caphalosporins First Second Third Fouh Parenteral Cephalothin Cefuroxime Cefotaxime Cefepime Cefazolin Cefoxitin Ceftizoxime Cefpirome Ceftriaxone Ceftazidime Cefoperazone Oral Cephalexin Cefaclor Cefixime Cepharidine Cefuroxime Cefopodoxine Cefadroxil Cefuroxime Cefdinir Antibacterial activity of cephalosporins First generation cephalosporins : - These are active against gram positive cocci including staphylococci. Second generation cephalosporins : ? More active against gram negative organism, Also has some activity against gram positive organisms. Some members also have activity against anaerobes e.g., cefotetan, Cefnzetazole and cefoxitin. Among the second generation cephalosporins, cefuroxime attains higher C.S.F. concentration. Third generation cephalosporins : - Have highly augumented activity against gram negative enterobacteriacea. Less active against gram (+ve) cocci and anaerobes. Highly resistant to [3 lactamases from negative bacteria. Some third generation cephalosporins have antipseudomonal activity : - e.g., Ceftazidime and cefoperazone. Ceftazidime + aminoglycoside is the treatment of choice for pseudomonas infections. Fouh generation cephalosporins : ? These drug possess activity against gram negative organisms (including pseudomonas) resistant to 3rd generation cephalosporins. Their efficacy against gram positive cocci is similar to 3rd generation compounds but an impoant point to remember is that they are not active against anaerobes. General features of Cephalosporins :- (Some impoant points to remember) Cephalosporin like other lactam antibiotics exe their action by inhibiting cell wall synthesis. Cephalosporins are excreted primarily by the kidney therefore they require dose reduction in renal failure. Probenecid slows the tubular secretion of most of the cephalosporins. Cefpiranzide, ceftriaxone and cefperazone are exceptions because they are excreted predominantly in the bile. Cefotaxime is deacetylated in vivo. The metabolite has less antimicrobial activity than the parent compound and is excreted by the kidneys. None qf the other cephalosporins appears to undergo appreciable metabolism. Several cephalosporins penetrate into C.S.F. in sufficient concentrations to be useful for the treatment of meningitis. These include: ? Cefotaxime Ceftriaxone Cefepime Cephalosporins also cross the placenta and they are found in high concentrations in synol and pericardial fluids. Penetration into the aqueous humour of the eye is relatively good after systemic administration of the third generation agents but penetration into the vitreous humour is poor. No cephalosporins is active against enterococcus fecalis, MRSA and listeria monocytogens. Concentrations in bile usually are high with those achieved after administration of cefoperazone and cefpiranzide being the highest. Adverse reactions Most common side effect of cephalosporin is hypersensitivity reaction. Immediate reactions such as anaphylaxis, bronchosposam and uicaria are observed. Cephalosporins have been implicated as potentially nephrotoxic agents (cephaloridine is considered the most nephrotoxic cephalosporin. It is no longer available in the united states). Cephalothin is another cephalosporin that produces renal toxicity, it causes acute tubular necrosis. Cephalosporins cause disulfiram like reaction (e.g., cefamandole, cefotetan, cefoperazone). These are caused by drugs which have rnethylthiotetrazole group. Cephalosporins have been associated with diarrhoea (is more frequent with cefoperazone because of its greater biliary excretion).