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Pharmacokinetics of meropenem in burn patients with infections caused by Gram-negative bacteria: Are we getting close to the right treatment?

Abstract：

OBJECTIVES:Infections caused by multidrug-resistant Gram-negative bacteria are associated with high mortality. A relevant concern is the efficacy of antibiotic therapy in burn patients in whom pathophysiological changes strongly influence pharmacokinetic (PK) parameters. This study aimed to describe the PK parameters of meropenem in a population of burn patients. METHODS:Blood samples were collected immediately before and 2 h and 5 h after the start of intravenous drug administration. Plasma meropenem concentrations were determined using an ultra-performance liquid chromatography-photodiode array method. RESULTS:Seventeen burn patients were enrolled in the study. Thirteen patients (76%) were treated with meropenem for infections byPseudomonas aeruginosa or Acinetobacter baumannii isolated from blood or wounds. Mean Cmax, Cmin, AUC0-24, half-life, drug clearance and volume of distribution were 28.9 mg/L, 3.7 mg/L, 280.2 mg h/L, 2.0 h, 19.0 L/h and 44.4 L, respectively. Six patients (35%) achieved a Cmin ≥3.3 mg/L and seven patients (41%) achieved a Cmax ≥ 28.4 mg/L, whilst nine patients (53%) achieved an AUC0-24 of >226 mg h/L. Given a minimum inhibitory concentration (MIC) of 0.5 mg/L, all patients satisfied the target AUC/MIC of >125, but when the MIC rises to 2 mg/L (the ECOFF), only five patients reached the desired AUC/MIC. Regarding fT>MIC at an MIC of 2 mg/L with a 2-h infusion time, 13 patients (76%) achieved the PK target (>75%). CONCLUSION:These data suggest that a combined 2-h infusion with a higher dosage of meropenem, including a loading dose, may be successful to achieve effective PK parameters.

journal_name

J Glob Antimicrob Resist

journal_title

Journal of global antimicrobial resistance

authors

Corcione S,D'Avolio A,Loia RC,Pensa A,Segala FV,De Nicolò A,Fatiguso G,Romeo M,Di Perri G,Stella M,De Rosa FG

doi

10.1016/j.jgar.2019.06.011

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

22-27

eissn

2213-7165

issn

2213-7173

pii

S2213-7165(19)30155-9

journal_volume

pub_type

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Pharmacokinetics of meropenem in burn patients with infections caused by Gram-negative bacteria: Are we getting close to the right treatment?