Cefazaflur

The values of the pseudo-first order hydrolysis rate constants in the pH range 1 to 10, and the pKa, were determined for cefazaflur in aqueous solution at 37 degrees C and ionic strength 0.2 M. A fluorimetric assay, based on alkaline hydrolysis at 100 degrees C, was also developed for this compound. The results are consistent with previously reported related properties of other monoprotic cephalosporins.

The in vitro activity of cefazaflur, a parenteral cephalosporin, was determined against 590 clinical isolates. Cefazaflur inhibited the majority of gram-positive cocci at concentrations below 1 mug/ml except for enterococci. The agent was as active as cefamandole or cefoxitin against most Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Although it inhibited a number of strains of Enterobacter, indole-positive Proteus, and Serratia resistant to cephalothin, it was much less active against these organisms than were cefamandole or cefoxitin.

Most cephalosporins can only be administered parenterally. Among agents that are absorbed from the gastrointestinal tract, those with bioavailabilities of 85 to 90% include cefroxadine, cefadroxil, cefsumide, cephalexin, cephradine, cephacetrile, and cefazaflur. Most cephalosporins are eliminated rapidly, with serum half-lives (t1/2s) of 1 to 2 hours. Exceptions are cefonicid with a t1/2 of 4.4 hours, cefpiramide with a t1/2 of 5.0 hours, and cefotetan with a t1/2 of 3.5 hours. The longest half-life is shown by ceftriaxone with a t1/2 of 8.5 hours. Cephalosporins are eliminated mostly by the kidneys, some with a substantial contribution from active tubular secretion, which is blocked by probenecid. The degree of metabolism varies. Only a few cephalosporins have a high biliary elimination. For example, with intravenously administered cefoperazone, about 70% appears in bile. High biliary elimination is also observed with cefmenoxime, ceftriaxone, cefbuperazone, and latamoxef (moxalactam). Because these are not appreciably absorbed from the gastrointestinal tract, the consequence is high intraintestinal concentrations of the drugs and a marked ensuing depression of the normal microflora with simultaneous emergence of resistant bacteria. The untoward ecological impact may even lead to Clostridium difficile-associated enterocolitis.