A new pharmacodynamic parameter, the composite recovery time (CRT), is described and used to calculate species-specific MIC breakpoints. Moxifloxacin data were used for illustration. This required determination of MICs, kill curves and post-antibiotic sub-MIC effect values. Thirteen test isolates included Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae. The concentration at which the CRT equals the dosing interval is the minimum effective concentration, and is effectively the breakpoint. The breakpoints were calculated as 2 mg/L for the pneumococci and quinolone-susceptible H. influenzae isolate, 1 mg/L for staphylococci and 0.5 mg/L for Enterobacteriaceae. Calculated pharmacodynamic breakpoints were very similar to traditional published MIC breakpoints.
- VITRO DYNAMIC-MODEL