Inhaled antibiotics improve clinical cure and reduce mortality in ventilator-associated pneumonia

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Critical care medicine Published June 4, 2026 Medically reviewed June 4, 2026 Study authors: Lyu Shan, Luo Jian, Liu Ping, Qin Xiaojing, He Wanjia, Jing Guoqiang, Ehrmann Stephan, Li Jie PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider adjunctive inhaled antibiotics for ventilator-associated pneumonia, noting benefits are based on meta-analysis with exploratory IV comparisons.

This is a systematic review and meta-analysis of adjunctive inhaled antibiotics for ventilator-associated pneumonia (VAP). The analysis pooled data from 1425 patients for the primary clinical cure outcome versus placebo or blank, and 1855 patients for all-cause mortality.

The meta-analysis found inhaled antibiotics significantly improved clinical cure (risk ratio [RR], 1.24; 95% CI, 1.07-1.43) and reduced all-cause mortality (RR, 0.84; 95% CI, 0.71-0.98) versus placebo or blank. In VAP-only patients, clinical cure (RR, 1.29; 95% CI, 1.10-1.52) and mortality (RR, 0.77; 95% CI, 0.65-0.90) were also improved. Microbiological eradication was improved (RR, 1.42; 95% CI, 1.27-1.58), and emergence of new drug resistance was reduced (RR, 0.20; 95% CI, 0.06-0.64).

Comparisons with intravenous (IV) antibiotics showed ventilator duration was shortened (mean difference, -2.11 days; 95% CI, -3.73 to -0.49 days; n=322) and nephrotoxicity was reduced (RR, 0.42; 95% CI, 0.26-0.68; n=292). ICU length of stay and ventilator duration versus placebo showed no difference.

The authors note exploratory analyses for IV comparisons are based on limited data. No differences in adverse events were found. Practice relevance warrants further high-quality trials, and benefits in mixed pneumonia populations or advantages beyond exploratory analyses should not be overstated.

Study Details

Study typeMeta analysis

Sample sizen = 1,425

EvidenceLevel 1

PublishedJun 2026

PMID41837717

View Original Abstract ↓

OBJECTIVES: To assess the effects of adjunctive inhaled antibiotics in treating ventilator-associated pneumonia (VAP). DATA SOURCES: We searched PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov through May 31, 2025. STUDY SELECTION: We included randomized controlled trials (RCTs) and nonrandomized studies comparing adjunctive inhaled antibiotics with placebo/blank or IV antibiotics for VAP treatment. DATA EXTRACTION: Two groups independently screened studies, extracted data, and assessed risk of bias. Analyses used random effects models. Subgroup analyses, meta-regression, trial sequential analysis, and the Grading of Recommendations Assessment, Development, and Evaluation were performed. DATA SYNTHESIS: We included 32 RCTs in the primary analysis and 41 non-RCTs in sensitivity analysis. Compared with placebo/blank, inhaled antibiotics significantly improved clinical cure (16 RCTs; n = 1425; risk ratio [RR], 1.24; 95% CI, 1.07-1.43) and reduced all-cause mortality (21 RCTs; n = 1855; RR, 0.84; 95% CI, 0.71-0.98), with consistent findings in sensitivity analyses including non-RCTs. These benefits were significant in VAP-only patients (clinical cure: 11 RCTs; n = 775; RR, 1.29; 95% CI, 1.10-1.52 and all-cause mortality: 15 RCTs; n = 1152; RR, 0.77; 95% CI, 0.65-0.90), but not in studies including mixed pneumonia populations. Meta-regression confirmed VAP-only population as a significant effect modifier. Inhaled antibiotics also improved microbiological eradication (20 RCTs; n = 1805; RR, 1.42; 95% CI, 1.27-1.58) and reduced emergence of new drug resistance (four RCTs; n = 182; RR, 0.20; 95% CI, 0.06-0.64). No differences were found in ICU length of stay, ventilator duration, or other adverse events. Compared with IV antibiotics, inhaled antibiotics shortened ventilator duration (three RCTs; n = 322; mean difference, -2.11 d; 95% CI, -3.73 to -0.49 d), and reduced nephrotoxicity (three RCTs; n = 292; RR, 0.42; 95% CI, 0.26-0.68). CONCLUSIONS: Compared with placebo/blank, adjunctive inhaled antibiotics improve clinical cure and microbiological eradication, and may reduce mortality, particularly in VAP-only patients. Exploratory analyses based on limited data suggest potential advantages over IV therapy, including shorter ventilator duration and lower nephrotoxicity, warranting further high-quality trials.