AUIC--a general target for the optimization of dosing regimens of antibiotics?

Abstract

To present a systematic evaluation of the are under the inhibitory curve (AUIC) approach for the optimization of antibiotic dosing schedules for three major antibiotic classes (beta-lactams, quinolones, aminoglycosides). It has been proposed that an AUIC over 24 hours of at least 125 may be an applicable target parameter for the optimization of antibiotic dosing schedules across these antibiotic classes. Some limitations of this approach are presented and discussed. A precise equation for the calculation of AUIC is derived. Moreover, a specific equation is derived for the situation that results in a trough concentration at the end of the dosing interval equal to the minimum inhibitory concentration (MIC). With the same three drugs used for deriving the target AUIC value (tobramycin, cefmenoxime, ciprofloxacin), different dosing regimens are simulated to obtain the target AUIC of 125. Very different serum concentration profiles can result in the same AUIC. In an example for cefmenoxime, dosing regimens of 1 g q6h and 4.2 g q24h resulted in equal AUIC values of 125, whereas the respective time above MIC differed dramatically (99% of the dosing interval for q6h vs. 36% for q24h). It does not seem valid to accept the proposed breakpoint AUIC target of at least 125 as an applicable value for determining the appropriate dosing schedule of these classes of antibiotics. Based on the limitations discussed about the AUIC approach, the same conclusion also holds for any other fixed AUIC breakpoint target value.