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Journal of Antimicrobial Chemotherapy (1999) 44, 471-476
© 1999 The British Society for Antimicrobial Chemotherapy

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

Kate A. Cholewkaa, Lisa L. Ioannides-Demosa,b,d, Lisa Lioliosa,c, Phillip Paulld, W. John Spicerc and Allan J. McLeana,f,*

a Department of Clinical Pharmacology, Alfred Hospital, Prahran, 3181 b Department of Pharmacy, Alfred Hospital, Prahran, 3181 c Department of Microbiology and Infectious Diseases, Alfred Hospital, Prahran, 3181 d Victorian Centre of Ambulatory Care Innovation, Alfred Hospital, Prahran, 3181 e Department of Biochemistry, St Vincent's Hospital, Melbourne , 3065 f University of Sydney Department of Medicine and Department of Geriatric Medicine, The Canberra Hospital, Garran, ACT 2605, Australia

We assessed the cephalosporin concentration–time curve area (AUC), peak concentration, maintained concentration and duration of exposure on in-vitro bactericidal effects on Escherichia coli NCTC 10418, using exposures modelling cephazolin clinical profiles after 1 g and 2 g im injection, equal AUC exposures (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 concentrations 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 profiles with equal or lower AUC (P < 0.05, ANOVA). Similar results applied to im comparisons with equal AUC exposures modelling extremes of concentration and time exposures. These results indicate a need for intermittent dosage to produce optimally effective profiles, and raise the possibility that these optimum dosing profiles may allow an extension of minimum interdose intervals beyond 8 h.

* Corresponding author. Tel: +61-2-6244-2577; Fax: +61-2-6244-4036; E-mail: allan_mclean{at}dpa.act.gov.au


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