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Comparable Effect of Two-Step Versus Extended Infusions on the Pharmacokinetics of Imipenem in Patients with Sepsis and Septic Shock

Authors
  • Huang, Yingzi1
  • Xu, Kang2
  • Zhan, Ying1
  • Zha, Xian1
  • Liu, Songqiao1
  • Xie, Jianfeng1
  • Liu, Lin1
  • Li, Qing1
  • Shao, Hua1
  • Yang, Yi1
  • 1 Southeast University, Nanjing, China , Nanjing (China)
  • 2 Chinese Academy of Medical Sciences, Nanjing, China , Nanjing (China)
Type
Published Article
Journal
Advances in Therapy
Publisher
Springer Healthcare
Publication Date
Apr 10, 2020
Volume
37
Issue
5
Pages
2246–2255
Identifiers
DOI: 10.1007/s12325-020-01339-5
Source
Springer Nature
Keywords
License
Yellow

Abstract

IntroductionThe present study aimed to compare the pharmacokinetic/pharmacodynamic (PK/PD) parameters of imipenem administered by two-step (50% delivered in a 30-min bolus, 50% for the following 90 min) or extended (administered continuously for 2 h) infusion.MethodsPatients with sepsis and septic shock were prospectively enrolled and randomized into four groups. Subjects in the two-step or extended groups were given two doses of imipenem (0.5 g q6h and 1.0 g q8h). The plasma imipenem concentrations were measured at given time points after the fifth dose. The PK/PD target was defined as the achievement of a fractional time above the minimal inhibitory concentration (MIC) of > 40%.ResultsThirty-five patients were eventually enrolled. No significant difference was observed in the percentage of patients achieving 40% T > MIC between the different infusion modes with the same dosage, although the two-step groups exhibited a significantly shorter Tmax compared with the extended groups (0.5 g q6h: 1.5 ± 0.8 vs. 2.0 ± 0.0 h; 1.0 g q8h: 1.0 ± 0.6 vs. 2.0 ± 0.0 h; both, p < 0.05). All four groups achieved 40% T > MIC when MIC was 0.5–4.0 μg/ml, but only regimens with a higher dose (1.0 g q8h) achieved target when MIC was 8 μg/ml.ConclusionThe two-step and extended regimens of imipenem are comparable to the PK/PD target in the treatment of sepsis and septic shock. A higher dose (1.0 g q8h) should be considered for target achievement at an MIC of > 8 μg/ml.Trial RegistrationClinicalTrials.gov identifier, NCT02616354.

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