Effectiveness and safety of adjunctive inhaled antibiotics for ventilator-associated pneumonia: A systematic review and meta-analysis of randomized controlled trials

Introduction: The efficacy and safety of adjunctive inhaled antibiotic therapy for ventilator-associated pneumonia (VAP) was systematically reviewed based on updated studies. Methods: We searched four databases and four clinical trial registration platforms to identify relevant studies published prior to May 19, 2020. Randomized controlled trials (RCTs) assessing adjunctive antibiotic inhalation treatment for VAP patients were eligible for this review. Two reviewers independently screened the articles and extracted the data. Information on inhaled therapy and clinical outcomes was collected. Study quality was assessed with the Cochrane risk of bias tool. The meta-analysis was conducted with Review Manager and R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines were used to evaluate the quality of evidence for each pooled outcome. Results: Eleven RCTs and 1210 patients were included in this analysis after the application of the inclusion and exclusion criteria. Compared with the use of intravenous injection alone, the use of adjunctive inhaled antibiotic therapy improved the rates of clinical cure (relative risk (RR) 1.13, 95% CI [1.02,1.26]) and microbiological eradication (RR 1.45, 95% CI [1.19,1.76]) in VAP patients. However, despite these improvements, mortality was not reduced (RR 1.00, 95% CI [0.82,1.21]). Adjunctive antibiotics delivered through the respiratory tract were not associated with a higher risk of renal impairment but were associated with an increased risk of bronchospasm (RR 2.74, 95% CI [1.31,5.73] during treatment. Conclusions: Adjunctive inhaled antibiotics improved the clinical outcomes in VAP patients, but the increased rates clinical cure and microbiological eradication were not associated with reduced mortality. The use of nebulized antibiotics is not supported by the currently available evidence as a routine therapeutic strategy for VAP. PROSPERO registration number: CRD42020186970. (c) 2021 Elsevier Inc. All rights reserved.