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Table 1 Documented rates of pharmacodynamic target non-attainment for various piperacillin dosing regimens in ARC patients

From: Increased dosing regimens of piperacillin-tazobactam are needed to avoid subtherapeutic exposure in critically ill patients with augmented renal clearance

Study Population PIP dosing regimen and administration ARC Probability of achieving a 100%fT>16mg/L in ARC patients
Andersen et al. [1] 22 non-critically ill patients 4 g every 8 h 3-min bolus eClCr > 130 mL/min N = 4/22 (18%) In ARC patients, probability of achieving a 100%fT> 16 mg/L was 0%.
Udy et al. [2] 48 critically ill patients 4 g/0,5 g every 6 h 20-min intermittent infusion 6-h mClCr as continuous variable Cumulative fraction of response decreased from 40% to less than 5% when CrCL values increased from 120 to 300 mL/min.
Carlier et al. [3] 60 critically ill patients 43 treated by PIP 4 g/0,5 g every 6 h 3-h extended infusion 24-h mClCr > 130 mL/min N = 29/60 (48%) In ARC patients, probability of achieving a 100%fT> 16 mg/L was 24% [no specific data for PIP].
Carrié et al. [4] 59 critically ill patients 173 PIP plasma samples 16 g/day continuously 160 mg/mL, 12-h infusion 24-h mClCr > 130 mL/min N = 36/59 (61%) Probability of achieving a 100%fT> 16 mg/L was 93% for 130 ≤ CrCL < 200 mL/min and 80% for ClCr > 200 mL/min.
Dhaese et al. [5] 110 critically ill patients 270 PIP plasma samples Continuous infusion, dosing regimen based on kidney function (16–24 g/day) 8-h mClCr > 130 mL/min N = 77/270 (32%) The fractional target attainment for the standard dosing regimen (16 g/day) decreased from 75 to 37% when CrCL increased from 150 to 300 mL/min.
  1. %fT> 16 mg/L fraction of time spent with an unbound concentration > 16 mg/L (representing the highest MIC for Pseudomonas as per the European Committee on Antimicrobial Susceptibility Testing), ARC augmented renal clearance, eClCr estimated creatinine clearance (Cockroft and Gault), mClCr measured creatinine clearance, FTA fractional target attainment, MIC minimal inhibitory concentration, PIP piperacillin