Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
Int J Antimicrob Agents. 2024 Oct;64(4):107293. doi: 10.1016/j.ijantimicag.2024.107293. Epub 2024 Aug 2.
The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited.
This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed.
Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69-133.78) and 33.82 (0.83-126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were >2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low.
Inhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.
多重耐药革兰氏阴性菌(MDR GNB)引起的肺炎发病率不断上升,给公共健康带来了巨大负担。吸入联合静脉多黏菌素已成为一种可行的治疗选择。然而,针对静脉和吸入多黏菌素 B(PMB)的药代动力学研究有限。
本研究纳入 2022 年 3 月 1 日至 11 月 30 日浙江大学医学院附属第一医院重症监护病房收治的 7 例 MDR GNB 引起肺炎的患者,采用静脉联合吸入 PMB 治疗。回顾性分析 PMB 的临床疗效和治疗药物监测数据。
PMB 在 ELF 中的中位浓度分别为 0、2、6 和 12 h 的 7.83(0.72-66.5)、116.72(17.37-571.26)、41.1(3.69-133.78)和 33.82(0.83-126.68)mg/L,明显高于血清中的浓度。PMB 在 ELF 中的浓度在 0、2、6 和 12 h 时均高于从患者分离的病原体的最低抑菌浓度。大多数患者的 PMB 血浆稳态浓度>2 mg/L。57.14%的患者治愈,71.43%的患者微生物学反应良好。PMB 的不良反应发生率低。
吸入联合静脉 PMB 可达到较高的 ELF 浓度和良好的临床疗效,且不良反应发生率无增加。这种治疗方法有望成为治疗多重耐药革兰氏阴性菌引起肺炎的患者的一种选择。