Optimal cefotaxime dosing for gram-negative bacteremia: effective trough serum bactericidal titers and drug concentrations 8 and 12 hr after 1- or 2-gm infusions.

Thirteen adult patients (47-81 yr) with gram-negative bacteremia and normal (less than or equal to 1.5 mg/dl) serum creatinines were treated with 1 or 2 gm of cefotaxime every 8 or 12 hr. The infecting organisms were Escherichia coli (9 strains), Klebsiella pneumoniae (2 strains), and one isolate of Salmonella enteritidis and Serratia marcescens. All patients recovered without any serious sequelae. The range of MICs for cefotaxime and desacetyl-cefotaxime were 0.015-0.25 micrograms/ml and 0.015-4.0 micrograms/ml, respectively. The MBC values for cefotaxime and desacetyl-cefotaxime were identical to the MIC values except for two strains. The trough levels of cefotaxime varied from 65.9 to 1.1 micrograms/ml. The serum concentration of desacetyl-cefotaxime varied from 84 to less than 1.0 microgram/ml. All corresponding trough serum inhibitory activities (SIA) were greater than or equal to 1:32. Comparisons of calculated and directly measured serum bactericidal activity (SBA) and SIA results suggest an additive and occasional synergistic benefit of the cefotaxime desacetyl metabolite. This study supports the clinical efficacy and cost-effectiveness of 8- and 12-hr dosing intervals for cefotaxime against bacteremic gram-negative strains having the usual high susceptibility (MICs, less than or equal to 0.25 micrograms/ml) to the newer cephalosporins.