Steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients

The study objective was to evaluate steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Fourteen hospitalised patients weighing >120 kg received piperacillin/tazobactam 4.5 g every 8 h (q8h) or 6.75 g q8h infused over 4 h. Blood samples were collected at steady-state and drug concentrations were determined. Pharmacokinetic parameters were estimated and 5000-patient Monte Carlo simulations were performed for four prolonged-infusion dosing regimens. The probability of target attainment (PTA) for ≥50% fT > MIC was calculated for piperacillin at various MICs, and the PTA for fAUC0-24 ≥ 96 mg h/L was calculated for tazobactam. Mean ± S.D. patient demographics were: age 49 ± 10 years; weight 161 ± 29 kg; and body mass index 52.3 ± 10.8 kg/m2. For piperacillin and tazobactam, respectively, the mean ± S.D. elimination rate was 0.440 ± 0.177 h−1 and 0.320 ± 0.145 h−1, volume of distribution was 33.4 ± 14.0 L (0.21 ± 0.07 L/kg) and 37.5 ± 15.3 L (0.23 ± 0.08 L/kg), and systemic clearance was 13.7 ± 5.2 L/h and 11.1 ± 4.2 L/h. For piperacillin, the PTA was ≥91% for doses ≥4.5 g q8h at MICs ≤ 16 μg/mL. For tazobactam, the PTA was 57%, 84% and 94% for doses of 4.5, 6.75 and 9.0 g q8h, respectively. The pharmacokinetics of piperacillin and tazobactam are altered in obese patients. To ensure adequate tazobactam concentrations for β-lactamase inhibition, it may be prudent to employ larger initial doses for empirical therapy in obese patients.