Early Target Attainment With Continuous Infusion Meropenem and Piperacillin/Tazobactam and Utilization of Therapeutic Drug Monitoring in Critically Ill Patients: A Retrospective Cohort Study From 2017 to 2020

Abstract

Objectives We analyzed the attainment of early pharmacological targets of continuous infusion meropenem and piperacillin/tazobactam and the use and effect of a real-time TDM program on subsequent dosing and target attainment in critically ill patients. Methods This was a single centre, retrospective study among patients hospitalized in the intensive care unit in a Swiss tertiary care hospital from 2017 to 2020. The primary outcome was target attainment [100% tT≥4xECOFF (Pseudomonas aeruginosa)] of continuous infusion meropenem and piperacillin/tazobactam within 72h after initiation of treatment. Results A total of 234 patients were included. Median first meropenem (n=186/234) and piperacillin (n=48/234) concentration was 21 mg/L (IQR 15.6-28.6) and 100.7 mg/L (IQR 64.0-160.2), respectively. Pharmacological target was attained in 95.7% (95% confidence interval 91.7-98.1) of patients receiving meropenem and 77.0% (95%CI 62.7-87.9) treated with piperacillin/tazobactam. In the univariable and multivariable logistic regression, body weight and estimated glomerular filtration rate were negatively associated with target attainment. Subsequently, meropenem dosage was decreased or stopped in 35/186 (18.8%) and 89/186 (47.9%) patients, respectively and increased in 2/186 (1.1%) patients. Conclusions Continuous infusion meropenem and piperacillin/tazobactam yielded excellent and moderate early pharmacological target attainment in critically ill patients, respectively. TDM was mainly used to decrease meropenem dosage.

Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review

“…In this scenario, adopting altered dosing strategies based on CI administration and implementing a therapeutic drug monitoring (TDM)-guided approach may significantly increase the likelihood of attaining aggressive PK/PD targets in critically ill patients (Guilhaumou et al, 2019). Specifically, the proportion of critical patients failing in attaining aggressive PK/PD targets with CI beta-lactams ranged from 5% to 28% (Richter et al, 2019;Chiriac et al, 2021;Gatti et al, 2022;Hagel et al, 2022;Dräger et al, 2023). A previous retrospective study including 166 critically ill patients (6.6% OLT recipients) reported a proportion of failure in attaining aggressive PK/PD targets at first TDM assessment with CI piperacillintazobactam and meropenem of 4.9% and 13.5%, respectively (Gatti et al, 2022).…”

Could an Optimized Joint Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin-Tazobactam Be a Valuable Innovative Approach for Maximizing the Effectiveness of Monotherapy Even in the Treatment of Critically Ill Patients with Documented Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections and/or Ventilator-Associated Pneumonia?

“…Several clinical studies showed that attaining an aggressive pharmacokinetic/ pharmacodynamic (PK/PD) target of 100%f T >4-8 × MIC with continuous infusion (CI) betalactams among critically ill patients was associated with both the maximization of clinical efficacy and the suppression of resistance development [13][14][15][16][17][18][19][20]. Failure in early attainment of this aggressive PK/PD target of piperacillin-tazobactam was shown to be as high as 80% during intermittent or extended infusion administration [21], and around 5-28% during CI administration [22][23][24][25][26]. All studies assessing aggressive PK/PD target attainment of piperacillin-tazobactam were based solely on piperacillin concentrations, without taking tazobactam exposure into account.…”