Cefotaxime and desacetylcefotaxime antimicrobial interactions. The clinical relevance of enhanced activity: a review

Abstract

This presentation reviews 15 years of in vitro, pharmacokinetic, and clinical data concerning the active metabolite of cefotaxime sodium, desacetylcefotaxime. This principle metabolite maintains an antimicrobial activity and spectrum superior to so-called "second-generation" cephalosporins, plus it has an extended serum elimination half-life. Furthermore, it penetrates well into various important body compartments. The metabolite enhances cefotaxime potency by additive or synergistic antimicrobial interactions that can significantly reduce cefotaxime minimum inhibitory concentrations (MICs) among oxacillin-susceptible staphylococci, Streptococcus species including pneumococci resistant to penicillin, anaerobes, enteric bacilli, Pseudomonas aeruginosa, and when tested in human serum, some enterococci. The high activity of cefotaxime alone and the contributions of desacetylcefotaxime to the drug's total antimicrobial value must be considered in reestablishing correct dosing of this "third-generation" cephalosporin. Physicians should use cefotaxime susceptibility tests to direct appropriate, cost-effective dosing and the selection of co-drugs when needed. Moreover, empiric cefotaxime regimen doses should also be reduced for some infections at sites where expected pathogen MICs remain low (< or = 2 micrograms/ml).