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Evaluation of imipenem pharmacokinetic/pharmacodynamic parameters and the impact on antimicrobial outcomes in critically ill patients
  • +3
  • Dan Zhang,
  • WenQian Chen,
  • WanYi Xu,
  • Wei Qin,
  • xianglin zhang,
  • pengmei li
WenQian Chen
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xianglin zhang
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pengmei li
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Peer review status:UNDER REVIEW

01 Jun 2020Submitted to British Journal of Clinical Pharmacology
08 Jun 2020Assigned to Editor
08 Jun 2020Submission Checks Completed
10 Jun 2020Reviewer(s) Assigned

Abstract

Aims: Imipenem is a widely used antibiotic for the treatment of critically ill patients with severe infections. Here, we present a translational pharmacokinetic/pharmacodynamic mathematical model to assess fT>MIC and evaluate the clinical outcomes of imipenem treatment in critically ill patients. Methods: Critically ill patients with severe infections were included in our study. Blood samples at different time points were collected after imipenem plasma concentration reached a steady state in vivo. A one-compartment model was used for pharmacokinetic profiles. PK/PD parameters were calculated separately with or without a mathematical model. Clinical results were mainly defined as the microbiological results. The resolution of fever and the decrease in PCT and WBC levels were also considered. Results: A total of 54 patients were enrolled in our study. The fT>MIC calculated by the mathematical model was 67.26±39.96%, and the fT>MIC was 73.75±23.11% without the model. The PK/PD parameters calculated between the two groups were not significantly different. Regarding clinical outcomes, 35 (64.3%) patients were defined as having clinical success. The fT>MIC was 83.33±12.90% in the clinical success group and 59.42±19.11% in the clinical failure group. The fT>MIC was significantly different between the two groups (p=0.022). Based on the regimens, the PCT level decreased to at least 20% of the peak level and the WBC level decreased during the first 3 days when patients’ fT>MIC was greater than 70%. Conclusion: The pharmacokinetic mathematical model may be used for PK/PD parameter evaluation. To treat critically ill patients, achieving fT>MIC greater than 70% may be necessary.