Cephalosporin clinical concentration-time profile modelling and in-vitro bactericidal effects on Escherichia coli

We assessed the cephalosporin concentration-time curve area (AUC), peak con centration, maintained concentration and duration of exposure on in-vitro b actericidal effects on Escherichia coli NCTC 10418, using exposures modelli ng cephazolin clinical profiles after 1 g and 2 g im injection, equal AUC e xposures (288 mg.h/L, 576 mg.h/L; 48 h) and constant exposures to 6, 12 and 24 mg/L. Cephalosporin dosage exposures based on maintenance of concentrat ions at multiples (6-24 times) of the MIC were not as effective in early or sustained (24 h) bactericidal effect as exposures modelling im injection p rofiles with equal or lower AUC (P < 0.05, ANOVA). Similar results applied to im comparisons with equal AUC exposures modelling extremes of concentrat ion and time exposures. These results indicate a need for intermittent dosa ge to produce optimally effective profiles, and raise the possibility that these optimum dosing profiles may allow an extension of minimum interdose i ntervals beyond 8 h.