Comparison of antimicrobial pharmacokinetic/pharmacodynamic breakpoints with EUCAST and CLSI clinical breakpoints for Gram-positive bacteria

Pharmacokinetic/pharmacodynamic analysis to evaluate ceftaroline fosamil dosing regimens for the treatment of community-acquired bacterial pneumonia and complicated skin and skin-structure infections in patients with normal and impaired renal function

“…A one-compartment pharmacokinetic model was assumed and the following equation was used, valid for i.v. infusions [16]:…”

“…Despite the accepted level of PTA being 90%, it is not yet well defined and different values (99%, 95% or 90%) have been used [16]. If 90% is used, this means that 10% of the population infected with a micro-organism that has the MIC used to determine the PK/PD index would probably not be covered [16].…”

“…If 90% is used, this means that 10% of the population infected with a micro-organism that has the MIC used to determine the PK/PD index would probably not be covered [16]. In order to decrease the risk of underexposure when considering a PTA of 90%, the EUCAST approach considers the total probability function irrespective of the target.…”

“…In order to decrease the risk of underexposure when considering a PTA of 90%, the EUCAST approach considers the total probability function irrespective of the target. In this way, the values for the mean of the population and the confidence intervals are displayed as a function of the MIC [16]. Over the years, EUCAST has included both the 95% CI and 99% CI, corresponding to a PTA of 97.5% and 99.5%, and has used the MIC values that resulted from these PTAs as the initial values for setting the PK/PD breakpoints [16].…”

“…In this way, the values for the mean of the population and the confidence intervals are displayed as a function of the MIC [16]. Over the years, EUCAST has included both the 95% CI and 99% CI, corresponding to a PTA of 97.5% and 99.5%, and has used the MIC values that resulted from these PTAs as the initial values for setting the PK/PD breakpoints [16]. Taking into account the EUCAST approach and the results of the current simulations (Fig.…”