Population pharmacokinetics and efficacy of tazobactam/piperacillin during continuous infusion in patients with community acquired and nosocomial infection

[Purpose] The population pharmacokinetics of piperacillin was investigated to verify the usefulness of continuous infusion of tazobactam/piperacillin (TAZ/PIPC) in patients with bacterial infection. Clinical efficacy was evaluated as a secondary endpoint. [Patients and method] This study was conducted from October 2005 to October 2006 in JA Aichi Showa Hospital. Hospitalized patients who were clinically or bacteriologically diagnosed as having bacterial infection were eligible. Patients received continuous infusion of TAZ/PIPC (5 g) over 24 h. Blood samples were obtained on the following day and 3-5 days later from patients who consented to the examination of the serum level of piperacillin. The population pharmacokinetics of piperacillin was generated by a nonlinear mixed effects model using the NONMEM program. [Results] A total of 47 patients were enrolled in the study (hepatobiliary infection, 19; urinary tract infection, 14; respiratory tract infection, 11; others, 3). Clinical response was excellent in 39 patients, good in 2, poor in 3, and not evaluated in 3 patients.The efficacy rate was 93.2% (41/44). Measurement of the blood levels was carried out in 14 patients. Population pharmacokinetic analysis was performed using a total of 107 points, including 14 patients (27 points) who received continuous infusion and 13 healthy volunteers (80 points) who received 30-minutes infusion of TAZ/PIPC. The 2-compartment model fitted best for the analysis of PK. The final formulae used for the mean population parameters were: CL (L/h) = 17.0 × [Ccr (mL/ min)/70] ^0.499, V ₁ (L) = 11.7, Q (L/h) = 3.25 and V ₂ (L) = 4.55. The steady-state concentration of piperacillin calculated from these pharmacokinetic parameters was 9.69 μg/mL, on average. [Conclusion] The estimated PIPC concentration at steady-state during continuous infusion of TAZ/PIPC in this study was high enough to overcome the main pathogens causing infections of urinary tract, biliary tract and respiratory tract, which supports the clinical usefulness of this dosing method.