Mechanism of action, antimicrobial activity, pharmacology, adverse effects, and clinical efficacy of cefotaxime.

Cefotaxime sodium, a parenteral cephalosporin antibiotic, exerts its bactericidal action through inhibition of bacterial cell wall synthesis. Chemical structure modifications have enabled this compound to be resistant to the action of Richmond I, III, IV, and V beta-lactamase enzymes. Excellent activity against many gram-negative bacilli, especially Enterobacteriaceae, has been demonstrated. Antipseudomonal activity is generally poor, however. Activity against gram-positive cocci, with the notable exception of Streptococcus fecalis, is adequate. Anaerobic activity is variable, particularly against Clostridia and Bacteroides species. Acute, subacute, and chronic toxicity studies in animals were generally unremarkable. No mutagenic effects or reproductive toxicity have been noted in animals. In man, cefotaxime is desacetylated to a microbiologically active metabolite. Urinary excretion is approximately 50-60% and 15-20% of a dose for the parent compound and desacetyl metabolite, respectively. The elimination half-life of cefotaxime is about one hour, with the total body clearance being approximately twice that of the renal clearance. Severe renal dysfunction causes a prolongation of the elimination half-life of cefotaxime and particularly desacetyl cefotaxime. A relatively low degree of protein binding in part attributes to a wide bodily distribution of cefotaxime. Cefotaxime is effective in a variety of infectious processes caused by susceptible organisms. Local reactions at the injection site and hypersensitivity phenomena are the most common adverse effects. Comparative trials attesting to cefotaxime's clinical utility over other parenteral cephalosporins or amino-glycosides are very limited. Based on the available evidence, cefotaxime should be most useful in combating serious gram-negative infections, because of its excellent activity against most of these organisms and its low toxicity profile.