Comparative in vitro studies on cefotaxime and desacetylcefotaxime

Abstract

After its parenteral administration in man, cefotaxime is partially metabolized to the desacetyl derivative (24-30% appearing in urine as desacetyl form). A detailed study was therefore carried out in vitro to compare the antibacterial activity against a wide range of clinical isolates and also the beta-lactamase stability of cefotaxime and desacetylcefotaxime, as well as other third-generation cephalosporins. The investigations of bacteriostatic and bactericidal activity were, in addition, extended to representative ureido-penicillins, cefuroxime, aminoglycosides and second-generation quinolones. Although cefotaxime was generally 4 to 8 times more active than its desacetyl derivative, smaller differences were observed against some strains of Enterobacteriaceae, Haemophilus influenzae and gonococci. A similar pattern was seen in relation to beta-lactamase stability, the parent antibiotic being generally more resistant to hydrolysis. Cefotaxime was, overall, the most active of the beta-lactam agents, except against pseudomonads, staphylococci and enterococci. In general, the antibiotic possessed comparable in-vitro efficacy to that of gentamicin, netilmicin and ciprofloxacin. Studies of combinations of cefotaxime and desacetylcefotaxime were carried out by the checkerboard method on solid media and also using a killing curve system in liquid media. A useful degree of synergy was observed against the majority of test organisms. This valuable effect could enhance the activity of cefotaxime in vivo, despite partial desacetylation.