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Comparable Effect of Two-Step Versus Extended Infusions on the Pharmacokinetics of Imipenem in Patients with Sepsis and Septic Shock.
Adv Ther ; 37(5): 2246-2255, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32277344
ABSTRACT

INTRODUCTION:

The 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.

METHODS:

Patients 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%.

RESULTS:

Thirty-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.

CONCLUSION:

The 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 REGISTRATION ClinicalTrials.gov identifier, NCT02616354.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Ensaio clínico controlado Idioma: Inglês Revista: Adv Ther Assunto da revista: Terapêutica Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China