Optimal treatment schedule of meropenem for adult patients with febrile neutropenia based on pharmacokinetic–pharmacodynamic analysis

Ohata, Yuka; Tomita, Yoshifumi; Nakayama, Mitsunobu; Tamura, Kazuo

doi:10.1007/s10156-011-0271-9

Cited by 14 publications

(5 citation statements)

References 18 publications

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“…Patients with FN comprise a diverse group of patients with significant variability in pharmacokinetic parameters . The lower CL observed in this pediatric oncology population is discordant with the pharmacokinetic findings in many other oncology studies, including the single study with piperacillin/tazobactam and two studies evaluating vancomycin pharmacokinetics in pediatric oncology patients suggesting a faster CL.…”

Section: Discussionsupporting

confidence: 65%

Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia

Cies

Jain

Kuti

2014

Pediatric Blood & Cancer

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Section: Discussionsupporting

confidence: 65%

Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia

Cies

Jain

Kuti

2014

Pediatric Blood & Cancer

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“…Other pharmacokinetic (PK) targets like targeting Cp more than four times of MIC for at least 40% of dosing interval (fT > 4 × MIC > 40) and continuous exposure of meropenem above the MIC (fT > MIC = 100 and fT > 4 × MIC = 100) have also been suggested. The fT > MIC can be increased by prolonging the duration of infusion for β-lactams [4]. Extended infusions (EI), with the dose delivered over several hours, and continuous infusions over 24 h have been proposed in place of the usual intermittent infusions given over a few minutes to an hour, to improve the pharmacokinetic/ pharmacodynamic (PK/PD) properties [5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria

Kothekar

Divatia

Myatra

et al. 2020

Ann. Intensive Care

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Background: Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100.Methods: Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used. Results:A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H). Conclusions:In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article' a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/ mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.

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“…In this study, most of the patients (92%) in whom the blood concentrations of MEPM were measured showed the a %TAM value of greater than 50% against 4 mg/ml of MIC, and a good clinical efficacy was also obtained in each case. A PK/PD simulation showed that the administration of a higher dose of MEPM could increase the %TAM [11], resulting in a higher concentration of MEPM in the local focal sites that may contribute to more favorable clinical outcomes. In fact, treatment with MEPM at 3 g/day has been shown to have good clinical effects against some respiratory infections, with an efficacy rate of 88% for VAP [12], 81%e89% for HAP [13,14], 93% for CAP [14].…”

Section: Discussionmentioning

confidence: 98%

Efficacy and safety of meropenem (3 g daily) in Japanese patients with refractory respiratory infections

Kawanami

Mukae

Noguchi

et al. 2014

Journal of Infection and Chemotherapy

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Optimal treatment schedule of meropenem for adult patients with febrile neutropenia based on pharmacokinetic–pharmacodynamic analysis

Cited by 14 publications

References 18 publications

Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia

Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia

Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria

Efficacy and safety of meropenem (3 g daily) in Japanese patients with refractory respiratory infections

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