Department of Anaesthesiology and Surgical Intensive Care, Hospital del Mar, IMIM (Hospital del Mar Research Institute), Paseo Marítimo 25-29, Barcelona, Spain.
Department of Pharmacy, Hospital del Mar, IMIM (Hospital del Mar Research Institute), Paseo Marítimo 25-29, Barcelona, Spain.
J Antimicrob Chemother. 2019 Nov 1;74(11):3268-3273. doi: 10.1093/jac/dkz356.
To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).
Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded.
Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed.
In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.
评估重症外科患者医院获得性肺炎（HAP）或呼吸机相关性肺炎（VAP）经雾化给予两种不同高剂量黏菌素甲磺酸钠后的血浆中形成的黏菌素药代动力学和安全性。
对接受两种不同剂量黏菌素甲磺酸钠雾化治疗（3MIU/8h 与 5MIU/8h）的肺炎重症外科患者测量血浆中形成的黏菌素浓度。记录可能与黏菌素甲磺酸钠雾化相关的不良事件。
共纳入 27 例患者（3MIU/8h 组 15 例，5MIU/8h 组 12 例）。3MIU/8h 组 8 例（53.3%）和 5MIU/8h 组 7 例（58.3%）患者的黏菌素血浆浓度无法定量（<0.1mg/L）。雾化前和雾化后 1、4 和 8h 时，3MIU/8h 组的可定量黏菌素血浆浓度中位数（IQR）分别为 0.17（0.12-0.33）、0.20（0.11-0.24）、0.17（0.12-0.23）和 0.17（0.11-0.32）mg/L，5MIU/8h 组分别为 0.20（0.11-0.35）、0.24（0.12-0.44）、0.24（0.10-0.49）和 0.23（0.11-0.44）mg/L，两组在任何时间均无差异。两组各有 3 例患者在雾化治疗期间出现肾功能损害，但不太可能与黏菌素甲磺酸钠治疗有关。黏菌素甲磺酸钠雾化治疗耐受良好，未观察到支气管痉挛或神经毒性事件。
在接受高剂量黏菌素甲磺酸钠雾化治疗的 HAP 或 VAP 重症患者的这项有限观察性病例系列研究中，全身暴露量很小，且治疗耐受良好。
