STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens. The regimens compared were piperacillin 4.0 g-tazobactam 0.5 g administered every 8 hours, and piperacillin 3.0 g-tazobactam 0.375 g administered every 6 hours. DESIGN: Multiple-dose, open-label, randomized, crossover study. SETTING: Clinical research center at Hartford Hospital. SUBJECTS:Twelve healthy volunteers. INTERVENTION: The two dosing regimens for piperacillin-tazobactam were administered intravenously in crossover design. Blood was sampled after the third dose. MEASUREMENTS AND MAIN RESULTS:Drug concentrations were determined by a validated high-performance liquid chromatography assay. The percentage of time above minimum inhibitory concentration (%T>MIC) for piperacillin was calculated for a range of MIC values. The maximum concentration (Cmax), area under the concentration-time curve (AUC0-tau), and total clearance of piperacillin differed significantly between the two study regimens, as did the Cmax, AUC0-tau, volume of distribution, and total clearance of tazobactam (p<0.05). The piperacillin 4.0 g-tazobactam 0.5 g regimen provided 40-50% T>MIC for MIC values 8-16 microg/ml; a similar value for the piperacillin 3.0 g-tazobactam 0.375 g regimen was 16-32 microg/ml. CONCLUSION: Although statistically significant differences in the pharmacodynamic profile were noted for the regimens, both provide adequate T>MIC against commonly encountered pathogens considered susceptible to piperacillin-tazobactam. However, for treatment of Pseudomonas aeruginosa infection, combination therapy or higher-dosage regimens (e.g., piperacillin 3.0 g-tazobactam 0.375 g every 4 hours, piperacillin 4.0 g-tazobactam 0.5 g every 6 hours, or continuous-infusion piperacillin 12 g-tazobactam 1.5 g/day) may be a prudent option when full MIC data are unavailable.
RCT Entities:
STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens. The regimens compared were piperacillin 4.0 g-tazobactam 0.5 g administered every 8 hours, and piperacillin 3.0 g-tazobactam 0.375 g administered every 6 hours. DESIGN: Multiple-dose, open-label, randomized, crossover study. SETTING: Clinical research center at Hartford Hospital. SUBJECTS: Twelve healthy volunteers. INTERVENTION: The two dosing regimens for piperacillin-tazobactam were administered intravenously in crossover design. Blood was sampled after the third dose. MEASUREMENTS AND MAIN RESULTS: Drug concentrations were determined by a validated high-performance liquid chromatography assay. The percentage of time above minimum inhibitory concentration (%T>MIC) for piperacillin was calculated for a range of MIC values. The maximum concentration (Cmax), area under the concentration-time curve (AUC0-tau), and total clearance of piperacillin differed significantly between the two study regimens, as did the Cmax, AUC0-tau, volume of distribution, and total clearance of tazobactam (p<0.05). The piperacillin 4.0 g-tazobactam 0.5 g regimen provided 40-50% T>MIC for MIC values 8-16 microg/ml; a similar value for the piperacillin 3.0 g-tazobactam 0.375 g regimen was 16-32 microg/ml. CONCLUSION: Although statistically significant differences in the pharmacodynamic profile were noted for the regimens, both provide adequate T>MIC against commonly encountered pathogens considered susceptible to piperacillin-tazobactam. However, for treatment of Pseudomonas aeruginosa infection, combination therapy or higher-dosage regimens (e.g., piperacillin 3.0 g-tazobactam 0.375 g every 4 hours, piperacillin 4.0 g-tazobactam 0.5 g every 6 hours, or continuous-infusion piperacillin 12 g-tazobactam 1.5 g/day) may be a prudent option when full MIC data are unavailable.
Authors: Seth R Bauer; Charbel Salem; Michael J Connor; Joseph Groszek; Maria E Taylor; Peilin Wei; Ashita J Tolwani; William H Fissell Journal: Clin J Am Soc Nephrol Date: 2012-01-26 Impact factor: 8.237
Authors: Ana Motos; Joseph L Kuti; Gianluigi Li Bassi; Antoni Torres; David P Nicolau Journal: Antimicrob Agents Chemother Date: 2019-01-29 Impact factor: 5.191
Authors: Catharine C Bulik; Pamela R Tessier; Rebecca A Keel; Christina A Sutherland; David P Nicolau Journal: Antimicrob Agents Chemother Date: 2011-11-07 Impact factor: 5.191
Authors: Thomas P Lodise; Ben Lomaestro; Keith A Rodvold; Larry H Danziger; George L Drusano Journal: Antimicrob Agents Chemother Date: 2004-12 Impact factor: 5.191
Authors: Maxwell J Lasko; Allison M Conelius; Oscar K Serrano; David P Nicolau; Joseph L Kuti Journal: Antimicrob Agents Chemother Date: 2020-11-17 Impact factor: 5.191
Authors: Dagan O Lonsdale; Emma H Baker; Karin Kipper; Charlotte Barker; Barbara Philips; Andrew Rhodes; Mike Sharland; Joseph F Standing Journal: Br J Clin Pharmacol Date: 2018-11-26 Impact factor: 4.335
Authors: Vidmantas Petraitis; Ruta Petraitiene; Povilas Kavaliauskas; Ethan Naing; Andrew Garcia; Christina Sutherland; Aki Yoneda Kau; Nicholas Goldner; Christopher Bulow; David P Nicolau; Thomas J Walsh Journal: Antimicrob Agents Chemother Date: 2021-08-30 Impact factor: 5.191
Authors: T W Felton; W W Hope; B M Lomaestro; J M Butterfield; A L Kwa; G L Drusano; T P Lodise Journal: Antimicrob Agents Chemother Date: 2012-05-14 Impact factor: 5.191