The use of inhaled antibiotics for treating pneumonia in invasively ventilated patients offers a direct approach, allowing for high local concentrations of the drug in the lower respiratory tract while simultaneously reducing systemic toxicity. However, the real efficacy and safety of nebulized antibiotics remain unclear. The aim of the present is to assess among critically adult patients with pneumonia and invasive ventilation, whether receiving adjuvant inhaled antibiotics improves the rate of microbiological eradication. A comprehensive literature search of randomized clinical trials (RCTs) was conducted (from inception until September 20, 2024, PROSPERO-CRD592906) across Medline, Embase, and Scopus. Randomized controlled trials, enrolling intensive care units (ICU) patients with pneumonia and comparing nebulized antimicrobial therapy (inhaled group) with intravenous antimicrobial treatment or intravenous antimicrobial therapy plus inhaled placebo (control group), were included. The primary outcome was the rate of microbiological eradication after treatment. Secondary outcomes were the rate of clinical recovery, the incidence of drug-related adverse events, ICU and hospital mortality. A qualitative analysis was conducted according to the GRADE framework. Data were pooled using an odds-ratio analysis. The heterogeneity and reliability of our results were evaluated using the I2-statistic and trial sequential analysis (TSA), respectively. A total of 11 RCTs (1472 patients) met the inclusion criteria. Compared to controls, the use of adjuvant inhaled antibiotics determined a greater rate of microbiological eradication (OR 2.63, 95% CI 1.36–5.09; low certainty of evidence). The TSA confirmed the reliability of our primary outcome. Moreover, nebulized antibiotics increased the risk of bronchospasm (OR 3.15, 95% CI 1.33–7.47; high evidence), while nephrotoxicity, clinical recovery, ICU and hospital survival (either in the case of pneumonia caused by MDR bacteria or not) were not different between groups. In conclusion, compared to the sole intravenous therapy, the use of adjuvant inhaled antibiotics for treatment of pneumonia in invasively ventilated critically ill patients was associated with a greater incidence of microbiological eradication (low GRADE and high risk of publication bias), but not with clinical recovery and survival.

中文翻译：

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吸入抗生素治疗重症监护病房有创通气患者肺炎：随机临床试验的荟萃分析和试验序贯分析


使用吸入抗生素治疗有创通气患者的肺炎提供了一种直接的方法，允许药物在下呼吸道局部浓度较高，同时降低全身毒性。然而，雾化抗生素的真正疗效和安全性仍不清楚。本综述的目的是评估患有肺炎和有创通气的危重成年患者，接受辅助吸入抗生素是否能提高微生物根除的速度。在 Medline、Embase 和 Scopus 中对随机临床试验 （RCT） 进行了全面的文献检索（从建库到 2024 年 9 月 20 日，PROSPERO-CRD592906）。纳入随机对照试验，纳入重症监护病房 （ICU） 肺炎患者，并将雾化抗菌治疗（吸入组）与静脉注射抗菌治疗或静脉注射抗菌治疗加吸入安慰剂（对照组）进行比较。主要结局是治疗后微生物根除率。次要结局是临床恢复率、药物相关不良事件的发生率、ICU 和住院死亡率。根据 GRADE 框架进行定性分析。使用比值比分析合并数据。我们结果的异质性和可靠性分别使用 I2 统计量和试验序贯分析 （TSA） 进行评估。共有 11 项 RCT （1472 名患者） 符合纳入标准。与对照组相比，使用辅助吸入抗生素决定了更高的微生物根除率（OR 2.63,95% CI 1.36–5.09;低质量证据）。TSA 证实了我们主要结局的可靠性。 此外，雾化抗生素增加了支气管痉挛的风险（OR 3.15,95% CI 1.33-7.47;高证据），而肾毒性、临床恢复、ICU 和住院生存率（无论是否由 MDR 细菌引起的肺炎）在组间没有差异。总之，与单独的静脉注射治疗相比，使用辅助吸入抗生素治疗有创通气危重症患者的肺炎与较高的微生物根除发生率 （低 GRADE 和高发表偏倚风险） 相关，但与临床恢复和生存率无关。