黏菌素钠稀释液体积对呼吸机相关性肺炎多重耐药菌感染患者气溶胶特性及药代动力学的影响。

Influence of diluent volume of colistimethate sodium on aerosol characteristics and pharmacokinetics in ventilator-associated pneumonia caused by MDR bacteria.

机构信息

Department of Pharmacology and CIC-1421, F-75013, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France.

Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France.

出版信息

J Antimicrob Chemother. 2018 Jun 1;73(6):1639-1646. doi: 10.1093/jac/dky044.

DOI:10.1093/jac/dky044

PMID:29506194

Abstract

OBJECTIVES

Nebulized colistimethate sodium (CMS) can be used to treat ventilator-associated pneumonia caused by MDR bacteria. The influence of the diluent volume of CMS on aerosol delivery has never been studied. The main objectives of the study were to compare aerosol particle characteristics and plasma and urine pharmacokinetics between two diluent volumes in patients treated with nebulized CMS.

METHODS

A crossover study was conducted in eight patients receiving nebulized CMS every 8 h. After inclusion, nebulization started with 4 million international units (MIU) of CMS diluted either in 6 mL (experimental dilution) or in 12 mL (recommended dilution) of normal saline in a random order. For each diluent volume, CMS aerosol particle sizes were measured and plasma and urine samples were collected every 2 h. Nebulization time and stability of colistin in normal saline were assessed.

RESULTS

The mass median aerodynamic diameters were 1.4 ± 0.2 versus 0.9 ± 0.2 μm (P < 0.001) for 6 and 12 mL diluent volumes, respectively. The plasma area under the concentration-time curve from 0 to 8 h (AUC0-8) of colistinA+B was 6.6 (4.3-17.0) versus 6.7 (3.6-14.0) μg·h/mL (P = 0.461) for each dilution. The total amount of colistin and CMS eliminated in the urine represented, respectively, 17% and 13% of the CMS initially placed in the nebulizer chamber for 6 and 12 mL diluent volumes (P = 0.4). Nebulization time was shorter [66 (58-75) versus 93 (69-136) min, P = 0.042] and colistin stability was better with the 6 mL diluent volume.

CONCLUSIONS

Nebulization with a higher concentration of CMS in saline (4 MIU in 6 mL) decreases nebulization time and improves colistin stability without changing plasma and urine pharmacokinetics or aerosol particle characteristics for lung deposition.

摘要

目的

黏菌素甲磺酸钠（CMS）雾化吸入可用于治疗多重耐药菌引起的呼吸机相关性肺炎。CMS 稀释剂体积对气溶胶输送的影响从未被研究过。本研究的主要目的是比较两种稀释剂体积在接受 CMS 雾化治疗的患者中的气溶胶颗粒特征以及血浆和尿液药代动力学。

方法

对 8 例每 8 小时接受 CMS 雾化吸入的患者进行交叉研究。纳入后，CMS 以 400 万国际单位（MIU）的剂量分别用 6 毫升（实验组）或 12 毫升（推荐组）生理盐水稀释，以随机顺序开始雾化。对于每种稀释剂体积，测量 CMS 气溶胶颗粒大小，并每 2 小时采集血浆和尿液样本。评估 CMS 在生理盐水的雾化时间和稳定性。

结果

质量中值空气动力学直径分别为 1.4±0.2μm和 0.9±0.2μm（P<0.001），分别对应 6 毫升和 12 毫升稀释剂体积。CMS 药代动力学参数中，AUC0-8（0 到 8 小时的血浆浓度-时间曲线下面积）分别为 6.6（4.3-17.0）μg·h/mL 和 6.7（3.6-14.0）μg·h/mL（P=0.461）。对于每种稀释剂，尿液中排出的总(colistinA+B)和 CMS 分别占初始放置在雾化器室的 CMS 总量的 17%和 13%（P=0.4）。6 毫升稀释剂体积的雾化时间更短[66（58-75）min 与 93（69-136）min，P=0.042]，CMS 稳定性更好。