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Meropenem Dosing Based on a Population Pharmacokinetic–Pharmacodynamic Model in Elderly Patients with Infection of the Lower Respiratory Tract

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Abstract

Background

Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli.

Objective

We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI.

Methods

In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG). The latter received meropenem according to a regimen decided by the attending physician. The SG received individualized meropenem therapy with a dosing strategy based on software developed from a meropenem population PK/PD model. The primary endpoint was clinical response to meropenem therapy. Secondary endpoints were the amount of antibiotics used and bacteriologic response.

Results

Klebsiella pneumoniae was the most common pathogen (32.9%), followed by Pseudomonas aeruginosa (30.4%) and Escherichia coli (17.7%). A total of 63 (79.7%) patients achieved clinical success. Prevalence of clinical success was significantly higher in the SG than in the CG (89.7 vs. 70.0%; p = 0.029). The daily dose of meropenem was significantly lower in the SG than in the CG (1.5 vs. 2.0 g; p = 0.017). A total of 52 (65.8%) patients experienced bacteriologic success, the median duration of meropenem therapy was 9 days, and the median total dose of meropenem was 18.0 g. There were no significant differences between the groups in these parameters.

Conclusions

A strategy for meropenem dosing based on a population PK/PD model can improve clinical response and avoid overtreatment in elderly patients with an LRTI.

ClinicalTrials.gov registration number NCT01944319.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Peking University Third Hospital, No. 49 North Garden Road., Haidian District, Beijing, 100191, China

    Qing-Tao Zhou, Bei He, Ning Shen, Ying Liang & Li-Na Sun

Authors
  1. Qing-Tao Zhou
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  2. Bei He
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  3. Ning Shen
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  4. Ying Liang
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  5. Li-Na Sun
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Corresponding author

Correspondence to Bei He.

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Funding

This study was supported by the Capital Medical Development Research Foundation (project number 2009-2025).

Conflict of interest

The authors have no conflicts of interest that are directly relevant to the content of this study.

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Zhou, QT., He, B., Shen, N. et al. Meropenem Dosing Based on a Population Pharmacokinetic–Pharmacodynamic Model in Elderly Patients with Infection of the Lower Respiratory Tract. Drugs Aging 34, 115–121 (2017). https://doi.org/10.1007/s40266-016-0431-9

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