For piperacillin, the probability of target attainment for at least 50% of free drug T > MIC was at least 91% for doses of at least 4.5 g every 8 h at MICs of 16 μg/ml or less [10 ▪].
To evaluate the forgiveness criterion, the success of target attainment for each simulated patient was evaluated with a perfect adherence profile and an imperfect adherence profile.
However, it is important to note that most studies [ 28- 31] demonstrated a poor probability of target attainment for the levofloxacin 500 mg QD regimen when MICs are 1 mcg/ml or more.
The probability of target attainment for Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, Aspergillus fumigatus, A. niger, and A. terreus were evaluated for a goal fAUC/MIC >25 or >35 at a voriconazole loading dose of 6 mg/kg IV every 12 hours and maintenance dosages of 4 and 6 mg/kg every 12 hours.
For tazobactam, the probability of target attainment was 57, 84, and 94% for doses of 4.5, 6.75, and 9.0 g every 8 h, respectively [10 ▪].
A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values.
Indeed, for an intermittent bolus administration, a 4gx4 dose is associated with a very low probability of target attainment, even for the lowest PK/PD target of T > MIC = 50%[32]].
The PK/PD cutoff is the MIC, at which the probability of target attainment (PTA) for 3-log10-unit decrease equals 90% under clinical recommended dose.
Monte Carlo simulation (Crystal Ball version 7, Oracle Corporation, Redwood Shores, CA, USA) was used to calculate probability of target attainment (PTA) for pharmacodynamic goals.
For the illustrative example, the probability of target attainment with imperfect adherence (Pip) was 0.38 and the probability of target attainment with perfect adherence (Pp) was 0.62 yielding a relative forgiveness (RF) of 0.38.
