Inhaled alone versus inhaled plus intravenous polymyxin B for the treatment of pneumonia due to carbapenem-resistant gram-negative bacteria: A prospective randomized controlled trial

IF 4.9 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents Pub Date : 2025-02-27 DOI:10.1016/j.ijantimicag.2025.107483

Yu Cheng , Lili Zhou , Danjie Wang , Xueyong Li , Rongqi Lin , Junnian Chen , Fuquan Tu , Yiqin Lin , Wenwei Wu , Maobai Liu , Hui Zhang , Hongqiang Qiu

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引用次数: 0

Abstract

Objectives

Infections due to carbapenem-resistant Gram-negative bacteria (CR-GNB) are associated with considerable morbidity and mortality. Polymyxin B (PMB) is a first-line agent for CR-GNB-associated pneumonia, but limited data exist on the clinical use of inhaled (IH) PMB.

Methods

A single-center, prospective randomized controlled trial was conducted in China to compare IH PMB alone with IH plus intravenous (IV) PMB between February 2022 and February 2024. The primary outcome was the clinical cure rate.

Results

Twenty-two evaluable patients were assigned to the IH group, and 56 patients were included in the IH+IV group. Baseline characteristics were comparable between the two groups. No significant differences were observed in clinical cure rates, favorable clinical outcomes, microbiological outcomes, all-cause mortality, or pneumonia-related mortality. However, IH PMB alone was associated with a lower incidence of nephrotoxicity (P = 0.030). IH PMB demonstrated significantly higher drug concentrations in the epithelial lining fluid (ELF) compared to systemic administration. Patients with immunosuppressive therapy (OR, 0.066; 95% CI, 0.010–0.433; P = 0.005), malignancies (OR, 0.112; 95% CI, 0.016–0.797; P = 0.029), and higher SOFA scores (OR, 0.693; 95% CI, 0.518–0.929; P = 0.014) were less likely to achieve favorable clinical outcomes. Conversely, higher PMB ELF 1-hour concentrations (OR, 1.085; 95% CI, 1.026–1.148; P = 0.004) were associated with more favorable clinical outcomes. The combination of these four indicators demonstrated excellent diagnostic performance (AUC = 0.882). Plasma 1-hour PMB concentrations showed acceptable predictive performance for nephrotoxicity (AUC = 0.766).

Conclusions

The potential benefits of IH PMB outweigh the risks, making it an effective treatment for CR-GNB-associated pneumonia in combination with other empirical antimicrobial agents.

Abstract Image

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单独吸入多粘菌素B与吸入加静脉注射多粘菌素B治疗耐碳青霉烯革兰氏阴性菌所致肺炎：一项前瞻性随机对照试验

碳青霉烯耐药革兰氏阴性菌（CR-GNB）引起的感染与相当高的发病率和死亡率相关。多粘菌素B （PMB）是治疗cr - gnb相关性肺炎的一线药物，但关于吸入（IH）多粘菌素B临床应用的数据有限。在2022年2月至2024年2月期间，在中国进行了一项单中心、前瞻性随机对照试验，比较IH PMB单独与IH加静脉（IV） PMB。主要观察指标为临床治愈率。22例可评估患者被分配到IH组，56例患者被纳入IH+IV组。两组患者的基线特征具有可比性。在临床治愈率、良好的临床结果、微生物学结果、全因死亡率或肺炎相关死亡率方面没有观察到显著差异。然而，单独IH PMB与较低的肾毒性发生率相关（P = 0.030）。与全身给药相比，IH PMB在上皮内膜液（ELF）中显示出明显更高的药物浓度。免疫抑制治疗患者(OR, 0.066；95% ci, 0.010-0.433；P = 0.005)，恶性肿瘤(OR, 0.112；95% ci, 0.016-0.797；P = 0.029)，较高的SOFA评分(OR, 0.693；95% ci, 0.518-0.929；P = 0.014)获得良好临床结果的可能性较小。相反，较高的PMB ELF 1小时浓度(OR, 1.085；95% ci, 1.026-1.148；P = 0.004)与更有利的临床结果相关。四项指标联合应用具有较好的诊断效果（AUC = 0.882）。血浆1小时PMB浓度对肾毒性具有可接受的预测性能（AUC = 0.766）。IH PMB的潜在益处大于风险，使其与其他经验性抗菌药物联合治疗cr - gnb相关性肺炎有效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Antimicrobial Agents 医学-传染病学

CiteScore

21.60

自引率

0.90%

发文量

176

审稿时长

36 days

期刊介绍： The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.