Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin–Tazobactam or Meropenem and Microbiological Outcome among Urologic Patients with Documented Gram-Negative Infections

Abstract

(1) Objectives: To describe the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin–tazobactam or meropenem monotherapy and microbiological outcome in a case series of urological patients with documented Gram-negative infections. (2) Methods: Patients admitted to the urology ward who were treated with CI piperacillin–tazobactam or meropenem monotherapy for documented Gram-negative infections and underwent real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program from June 2021 to May 2023 were retrospectively retrieved. Average steady-state (Css) piperacillin–tazobactam and meropenem concentrations were determined, and the free fractions (fCss) were calculated. Optimal PK/PD target attainments were defined as an fCss/MIC ratio >4 for CI meropenem and an fCss/MIC ratio of piperacillin >4 coupled with an fCss/CT ratio for tazobactam >1 for piperacillin–tazobactam (joint PK/PD target). The relationship between beta-lactam PK/PD targets and microbiological outcome was explored. (3) Results: Sixteen urologic patients with documented Gram-negative infections (62.5% complicated urinary tract infections (cUTI)) had 30 TDM-guided ECPAs. At first TDM assessment, beta-lactam dosing adjustments were recommended in 11 out of 16 cases (68.75%, of which 62.5% decreases and 6.25% increases). Overall, beta-lactam dosing adjustments were recommended in 14 out of 30 ECPAs (46.6%). Beta-lactam PK/PD target attainments were optimal in 100.0% of cases. Microbiological failure occurred in two patients, both developing beta-lactam resistance. (4) Conclusion: A TDM-guided ECPA program may allow for optimizing beta-lactam treatment in urologic patients with documented Gram-negative infections, ensuring microbiological eradication in most cases.

Keywords

• piperacillin–tazobactam
• meropenem
• urology
• Gram-negative infections
• PK/PD target attainment
• microbiological outcome