Comparison of in-vitro pharmacodynamics of once and twice daily ciprofloxacin

The pharmacodynamics of ciprofloxacin were explored in an in-vitro continuous bacterial culture model of infection, by simulating two oral dosing regimens; 0.5 g 12-hourly (bd) and 1 g 24-hourly (od). Three strains of Escherichia coli(ciprofloxacin MICs 0.03, 0.5 and 2 mg/L); two strains of Pseudomonas aeruginosa (MICs 0.09 and 1.5 mg/L), two strains of Staphylococcus aureus (MICs 0.12 and 1 mg/L) and two strains of Streptococcus pneumoniae (MICs 0.5 and 2 mg/L) were used. Three pharmacodynamic parameters, T> MIC, C-max/MIC and AUC/MIC (T = time, C-max = peak serum concentration, AUC = area under the curve), were compared with area under the bacterial-kill curve (AUBKC) (after transformation of the AUBKC) using a simple E-max or sigmoidal E-max model. AUBKC was taken to be the main antibacterial effect measure. The models were compared by inspection of residuals and Akaike information criterion. E-max models adequately described the relationship between AUC/MIC and AUBKC and between C-max/MIC and AUBKC, but not between T> MIC and AUBKC. All three pharmacodynamic parameters are related to each other but multiple regression analysis indicated that AUC/MIC was the best individual predictor of AUBKC. Despite this, comparison of od and bd regimens indicates some advantage to od in terms of early antibacterial effect. Serum concentration-time curve shape has some importance in determining antibacterial effect. These data indicate that for ciprofloxacin AUC/MIC ratio is not the sole determinant of antibacterial effect.