ArticleJournal of clinical pharmacology2025
Utilizing an Opportunistic Clinical Study and Population-Based Pharmacokinetic Models to Identify Rational Empiric Dosing Regimens for Piperacillin-Tazobactam in Critically Ill Patients.
Article in Journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A multicentre evaluation of pharmacokinetic/pharmacodynamic target attainment of piperacillin and tazobactam and the association with clinical outcomes in critically ill patients with sepsis and septic shock.The Journal of antimicrobial chemotherapy · 2026Article
- Pharmacokinetic-pharmacodynamic target attainment with continuous infusion piperacillin in patients admitted to the ICU with hospital-acquired pneumonia.Antimicrobial agents and chemotherapy · 2026Article
- Critical threshold target attainment rates for tazobactam combined with piperacillin among patients admitted to the ICU with hospital-acquired pneumonia.Antimicrobial agents and chemotherapy · 2026Article
- Inclusion of Women, Children, the Elderly, and Individuals With Underlying Medical Conditions: Prioritizing Vulnerable Populations in Clinical Research.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
Determining an effective dosing regimen for piperacillin-tazobactam in critically ill patients is challenging due to substantial pharmacokinetic variability caused by complex pathophysiological changes. To address this need, a prospective clinical study was conducted, which enrolled 112 critically ill patients and employed an opportunistic sampling strategy. Population modeling and simulation were performed to characterize the pharmacokinetics (PK) and probability of target attainment (PTA) of piperacillin-tazobactam under various dosing regimens. Both piperacillin and tazobactam final models were one-compartment models with zero-order input and first-order elimination. Significant covariates included lean body weight for piperacillin and creatinine clearance along with continuous renal replacement therapy (CRRT) for both drugs. Monte Carlo simulations demonstrated that continuous infusion can achieve higher PTA than intermittent and extended infusions. When considering the minimum inhibitory concentration (MIC) of 16 mg/L for Pseudomonas aeruginosa (a frequently encountered bacterial pathogen among critically ill patients) and a PK/PD target of 100% fT >MIC, continuous infusion of 6 g/day is recommended for critically ill patients with a CLcr <60 mL/min, 9 g/day for patients with CLcr in the range of 60 to 129 mL/min, and 12 g/day for patients with a CLcr ≥130 mL/min. In addition, extended infusion represents a good alternative, especially the 3 g q6h or 4 g q6h regimens which can achieve the designated European Committee on Antimicrobial Susceptibility Testing (EUCAST) non-species-related PK/PD breakpoint of 8 mg/L. Our study provided valuable insight into PTA outcomes, which, together with individual renal function of future patients and institution-specific piperacillin susceptibility patterns, may assist physicians when making dosing decisions.
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