Department of Critical Care Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, 253 Gongye Rd, Guangzhou, 510282, China.
Department of Intensive Care Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Crit Care. 2024 Jul 14;28(1):239. doi: 10.1186/s13054-024-05031-w.
The optimal administration of polymyxins for treating multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia remains unclear. This study aimed to systematically assess the efficacy and safety of three polymyxin-containing regimens by conducting a comprehensive network meta-analysis.
We comprehensively searched nine databases. Overall mortality was the primary outcome, whereas the secondary outcomes encompassed microbial eradication rate, clinical success, acute kidney injury, and incidence of bronchospasm. Extracted study data were analyzed by pairwise and network meta-analyses. Version 2 of the Cochrane risk-of-bias tool and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool were used to assess the risk of bias in randomized trials and cohort studies, respectively.
This study included 19 observational studies and 3 randomized controlled trials (RCTs), encompassing 3318 patients. Six studies with high risk of bias were excluded from the primary analysis. In the pairwise meta-analysis, compared to the intravenous (IV) polymyxin-containing regimen, the intravenous plus inhaled (IV + IH) polymyxin-containing regimen showed a significant decrease in overall mortality, while no statistically significant difference was found in the inhaled (IH) polymyxin-containing regimen. The network meta-analysis indicated that the IV + IH polymyxin-containing regimen had significantly lower overall mortality (OR 0.67; 95% confidence interval [CI] 0.50-0.88), higher clinical success rate (OR 1.90; 95% CI 1.20-3.00), better microbial eradication rate (OR 2.70; 95% CI 1.90-3.90) than the IV polymyxin-containing regimen, and significantly better microbial eradication rate when compared with the IH polymyxin-containing regimen (OR 2.30; 95% CI 1.30-4.20). Furthermore, compared with IV + IH and IV polymyxin-containing regimens, the IH polymyxin-containing regimen showed a significant reduction in acute kidney injury.
Our study indicates that among the three administration regimens, the IV + IH polymyxin-containing regimen may be the most effective for treating MDR-GNB pneumonia, with a significantly lower overall mortality compared to the IV regimen and a considerably higher microbial eradication rate compared to the IH regimen. The IH regimen may be considered superior to the IV regimen due to its substantially lower incidence of acute kidney injury, even though the reduction in overall mortality was not significant.
治疗多重耐药革兰氏阴性菌（MDR-GNB）肺炎的最佳多粘菌素给药方案仍不清楚。本研究旨在通过全面的网络荟萃分析来系统评估三种含多粘菌素方案的疗效和安全性。
我们全面检索了九个数据库。总死亡率是主要结局，而次要结局包括微生物清除率、临床成功率、急性肾损伤和支气管痉挛发生率。通过配对和网络荟萃分析分析提取的研究数据。使用 Cochrane 偏倚风险工具 2 版和干预非随机研究的偏倚风险（ROBINS-I）评估工具分别评估随机试验和队列研究的偏倚风险。
本研究纳入了 19 项观察性研究和 3 项随机对照试验（RCT），共纳入 3318 名患者。有 6 项研究存在高偏倚风险，因此被排除在主要分析之外。在成对荟萃分析中，与静脉注射（IV）含多粘菌素方案相比，静脉注射联合吸入（IV+IH）含多粘菌素方案显著降低了总死亡率，而吸入（IH）含多粘菌素方案则没有统计学意义。网络荟萃分析表明，IV+IH 含多粘菌素方案的总死亡率显著降低（OR 0.67；95%置信区间 [CI] 0.50-0.88），临床成功率更高（OR 1.90；95% CI 1.20-3.00），微生物清除率更好（OR 2.70；95% CI 1.90-3.90），与 IV 含多粘菌素方案相比，微生物清除率也显著提高（OR 2.30；95% CI 1.30-4.20）。此外，与 IV+IH 和 IV 含多粘菌素方案相比，IH 含多粘菌素方案可显著降低急性肾损伤的发生率。
本研究表明，在这三种给药方案中，IV+IH 含多粘菌素方案可能是治疗 MDR-GNB 肺炎最有效的方案，与 IV 方案相比，总死亡率显著降低，与 IH 方案相比，微生物清除率显著提高。由于 IH 方案的急性肾损伤发生率明显较低，即使总死亡率降低不显著，其可能优于 IV 方案。
