Cefoperazone activity

Cefpimizole (51) appears to be less active in vitro than cefotaxime and cefoperazone and to have a somewhat narrower activity spectrum although some strains of Pseudomonas are susceptible. It is not orally active, but its performance in vivo appears superior to what would be expected from its in vitro data. Its synthesis begins by acylation of cephaloglycin (48) with the bis acid chloride of imidazole-4,5-dicarboxylic acid (49) to give amide 50. The acetyl moiety at C-3 of this intermediate is displaced with 4-pyridineethanesulfonic acid and sodium iodide to give cef-pimazole (51) [16]. 

Parenterally administered cephalosporins that are metabolically stable and that are resistant to many types of jS-lactamases include eefuroxime, cefamandole, cefotaxime and cefoxitin, which has a 7a-methoxy group at R. Injectable cephalosporins with anti-pseudomonal activity include cefsulodin and cefoperazone. 

Third generation Examples are cefotaxime, cefoperazone, ceftazidime, ceftizoxime, ceftriaxone, cefdinir etc. This generation has greater Gramnegative activity but loses some Gram-positive potency. 

Urinary excretion is the major elimination path for most cephalosporins. When prescribing cephalosporins to patients with renal failure, practitioners must consider dose reduction or dose interval extension (Table 45.2). Renal tubular secretion contributes to the elimination of some cephalosporins, and an increase in cephalosporin plasma concentrations may occur when probenecid blocks renal tubular secretion of cephalosporins. Biliary elimination is important for some cephalosporins. Cefmetazole, cefoperazone (Cefobid), cefoxitin, and ceftriaxone achieve biliary concentrations greater than those in plasma. After parenteral administration of cefoperazone, 70% of the dose appears in the bile within 24 hours. Practitioners should decrease the dose of cefoperazone when prescribing for patients with hepatic failure or biliary obstruction. Metabolism is not a major elimination path for most cephalosporins. Cefotaxime is one of the few cephalosporins having an active metabolite, desacetyl cefotaxime. 

Third-generation Cefoperazone Broader activity against resistant gramnegative organisms some derivatives penetrate the blood-brain barrier. 

Moxalactam is active against most commonly encountered anaerobic bacteria (6,10,14,23-25,29,30,35-37) and is more active against certain strains than cefotaxime, cefoperazone, and cefoxitin. For many isolates, the concentration of moxalactam required for bactericidal activity is the same as or twofold greater than the MIC (23,27,28). For most bacterial strains, increasing the inoculum size has little or no effect on the MIC of moxalactam (6,9,10,13,16,21). 

These resemble the penicillins structurally, in mode of action and in general lack of toxicity. They are primarily excreted by the kidney by tubular secretion and some also by glomerular filtration (e.g. cephalothin) or only by glomerular filtration (e.g. cefazolin). Cefoperazone is excreted by the bile. Cefotaxime undergoes hepatic biotransformation to active metabolites. Hypersensitivity reactions are qualitatively similar to those of the penicillins, but the epileptogenic potential is less. 

Cefoperazone, like cefamandole, has the ability to induce epileptogenic activity, disulfiram-like activity, and hypoprothrombinemia. It appears that hypothrom-binemia occurs more frequently with cefoperazone than with other cephalosporins [45]. 

Renal clearance similar to penicillins, with active tubular secretion blocked by probenecid. Dose modification in renal dysfunction, except cefoperazone and ceftriaxone, which are largely eliminated in the bile. 

Kalman, D. Barriere, S.L. Johnson, B.L., Jr. Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid. Antimicrob.Agents Chemother., 1992, 36, 453-457... 

GENERAL FEATURES OF THE CEPHALOSPORINS Cephalosporins are excreted primarily by the kidney, and dosage should be decreased in patients with renal insufficiency. Cefpi-ramide (not available in U.S.) and cefoperazone are excreted predominantly in the bUe. Cefotaxime is deacetylated to a metabolite with less antimicrobial activity than the parent compound and excreted by the kidneys. The other cephalosporins do not undergo appreciable metabolism. 

B. Pharmacokinetics Several cephalosporins are available for oral use, but most are administered parenterally. Cephalosporins with side-chains may undergo hepatic metabolism, but the major elimination mechanism for drugs in this class is renal excretion via active tubular secretion. Cefoperazone and ceftriaxone are excreted mainly in the bile. Most first- and second-generation cephalosporins do not enter the cerebrospinal Uuid even when the meninges are in-Uamed. 

Cefmenoxime hydrochloride is a third generation cephalosporin antibiotic. Structurally, it possesses the (l-methyl-lH-tetrazoi-5-yl)thiomethyl moiety in the 3-position like several other compounds containing this structural element (moxalactam, cefoperazone, cefamandol), bleeding linked to vitamin K interaction has been reported. Cefmenoxime has activity similar to cefotaxime, ceftizoxime and moxalactam against E. coli, C. diversus, Klebsiella, P. Mirabilis, Salmonella, Shigella, Neiseria spp., S. pyogenes, S. Pneumoniae, and H. influenzae. It is relatively ineffective against Pseudomonas and Bacteroides. 

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