Comparative Beta-lactamase Hydrolysis of and Inhibition by 7-aminothiazolyl Alpha-methoxyimino Cephalosporins

Six 7-aminothiazolyl alpha-methoxyimino cephalosporins were found to be most variable in their ability to resist Type IV beta-lactamases (ceftizoxime, most stable and ceftriaxone, least stable), to inhibit Type I beta-lactamases (cefotaxime, the best inhibitor and desacetyl-cefotaxime, the least inhibition), to inhibit Enterobacteriaceae as measured by their minimum inhibitory concentrations (MICs), and in their published serum half-lives. The 3-position substituents appear to exert significant physical-chemical effects that influence the pharmacology, molecular enzyme stability and the antimicrobial activity of these compounds. However, we conclude that these differences are of minimal clinical consequence and that other more relevant factors for in vivo drug selection should be considered, including proven clinical efficacy and cost.