Experimental verification of the efficacy of optimized two-step infusion therapy with meropenem using an in vitro pharmacodynamic model and Monte Carlo simulation

Ken Eguchi, Katsunori Kanazawa, Takeshi Shimizudani, Keiji Kanemitsu, Mitsuo Kaku

研究成果: Article査読

13 被引用数 (Scopus)

抄録

In this study we compared the efficacy of a theoretically optimized two-step infusion therapy (OTIT; rapid first-step infusion and slow second-step infusion) to the efficacies of prolonged infusion therapy (PIT) and traditional 0.5 h infusion therapy (TIT) with meropenem against Pseudomonas aeruginosa using an in vitro pharmacodynamic model and a Monte Carlo simulation. In the in vitro pharmacodynamic model, the bactericidal effect against P. aeruginosa was evaluated for 8 h, which is the usual dosing interval of meropenem. It was confirmed that the durability of the bactericidal effect of OTIT (0.25-1 g/0.5 h + 0.25-1 g/4 h t.i.d.) was almost equal to that of PIT and superior to that of TIT (0.5-2 g/0.5-4 h t.i.d.). In addition, the initial bactericidal effects of OTIT were superior to those of the prolonged 4 h infusion. In the Monte Carlo simulation study, the probability of target attainments (PTAs) of all dosing regimens of OTIT at MICs of 2-8 μg/ml were apparently superior to those of TIT and 4- and 6 h-PIT, when the target therapeutic condition for serious life-threatening infections was the achievement of both the percentage of the dosing interval at which the drug concentration exceeds the MIC (%T >MIC) ≥ 50% and the peak level divided by the MIC (C max/MIC) ≥ 4. Especially, the PTAs of the dosing regimens of 0.25-1 g/0.5 h + 0.25-1 g/4-6 h were excellent at MICs of 2-8 μg/ml. Against recent clinical isolates of P. aeruginosa in Japan, the dosing regimens of OTIT provided higher PTAs compared with those of TIT and 4- and 6 h-PIT. These results suggested that OTIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of meropenem against serious life-threatening infections.

本文言語English
ページ(範囲)1-9
ページ数9
ジャーナルJournal of Infection and Chemotherapy
16
1
DOI
出版ステータスPublished - 2010 2月

ASJC Scopus subject areas

  • 微生物学(医療)
  • 薬理学(医学)
  • 感染症

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