The Efficacy and Safety of Inhaled Antibiotics for the Treatment of Bronchiectasis in Adults: Updated Systematic Review and Meta-Analysis

Abstract

Background: Inhaled antibiotics are recommended conditionally by international bronchiectasis guidelines for the treatment of patients with bronchiectasis, but results of individual studies are inconsistent. A previous meta-analysis demonstrated promising results regarding the efficacy and safety of inhaled antibiotics in bronchiectasis. Subsequent publications have supplemented the existing body of evidence further in this area.

Research question: To what extent do inhaled antibiotics demonstrate both efficacy and safety as a treatment option for adults with bronchiectasis?

Study design and methods: Systematic review and meta-analysis of randomized controlled trials of inhaled antibiotics in adult patients with bronchiectasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for eligible studies. Studies were included if they enrolled adults with bronchiectasis diagnosed by CT imaging and had a treatment duration of at least 4 weeks. The primary end point was exacerbation frequency, with additional key efficacy end points including severe exacerbations, bacterial load, symptoms, quality of life, and FEV₁. Data were pooled through random-effects meta-analysis.

Results: Twenty studies involving 3,468 patients were included. Inhaled antibiotics were associated with reduced number of patients with exacerbations (risk ratio, 0.85; 95% CI, 0.75-0.96), a slight reduction in exacerbation frequency (rate ratio [RR], 0.78; 95% CI, 0.68-0.91), a probable reduction in the frequency of severe exacerbations (RR, 0.48; 95% CI, 0.31-0.74), and a likely slight increase in time to first exacerbation (hazard ratio, 0.80; 95% CI, 0.68-0.94). Inhaled antibiotics likely lead to a slight increase in the Quality of Life Questionnaire-Bronchiectasis respiratory symptom score (mean difference, 2.51; 95% CI, 0.44-4.31) and may reduce scores on the St. George Respiratory Questionnaire (mean difference, -3.13; 95% CI, -5.93 to -0.32). Bacterial load consistently was reduced, but FEV₁ was not changed with treatment. Evidence suggests little to no difference in adverse effects between groups (OR, 0.99; 95% CI, 0.75-1.30). Antibiotic-resistant organisms likely were increased by treatment.

Interpretation: In this systematic review and meta-analysis, inhaled antibiotics resulted in a slight reduction in exacerbations, a probable reduction in severe exacerbations, and a likely slight improvement in symptoms and quality of life in adults with bronchiectasis.

Trial registry: International Prospective Register of Systematic Reviews; No.: CRD42023384694; URL: https://www.crd.york.ac.uk/prospero/.

Keywords: antibiotics; bronchiectasis; inhalation; meta-analysis; therapeutics.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses study flow diagram.

Figure 2

A, B, Forest plots showing frequency of exacerbations (A) and frequency of severe exacerbations (B). The weight of each study is the percentage of its contribution to the overall effect estimate. Weights of individual studies might not add up to the subtotal or overall weights because of rounding. Risk of bias is represented as low (+), unclear (?), or high (–). df = degrees of freedom; IV = inverse variance.

Figure 3

A, B, Forest plots showing of quality of life and symptom scales according to the Quality of Life Questionnaire-Bronchiectasis (QOL-B) (A) and the St. George Respiratory Questionnaire (SGRQ) (B). A negative score has been shown as a reduction in symptoms for ease of interpretation. In the original scales, a reduction in the scale indicates an improvement in symptoms with the SGRQ, but a worsening with the QOL-B. The weight of each study is the percentage of its contribution to the overall effect estimate. Weights of individual studies might not add up to the subtotal or overall weights because of rounding. Risk of bias is represented as low (+), unclear (?), or high (–). df = degrees of freedom; IV = inverse variance; M-H = Mantel-Haenszel.

Figure 4

Forest plot showing isolated bacteria with a minimum inhibitory concentration of more than the resistant breakpoint at the end of treatment. The weight of each study is the percentage of its contribution to the overall effect estimate. Weights of individual studies might not add up to the subtotal or overall weights because of rounding. Risk of bias is represented as low (+), unclear (?), or high (–). df = degrees of freedom; IV = inverse variance.

Figure 5

A, B, Forest plots showing treatment-emergent adverse effects leading to discontinuation (A) and bronchospasm events (B). The weight of each study is the percentage of its contribution to the overall effect estimate. Weights of individual studies might not add up to the subtotal or overall weights because of rounding. Risk of bias is represented as low (+), unclear (?), or high (–). Includes safety population. df = degrees of freedom; IV = inverse variance; M-H = Mantel-Haenszel.

Figure 5

A, B, Forest plots showing treatment-emergent adverse effects leading to discontinuation (A) and bronchospasm events (B). The weight of each study is the percentage of its contribution to the overall effect estimate. Weights of individual studies might not add up to the subtotal or overall weights because of rounding. Risk of bias is represented as low (+), unclear (?), or high (–). Includes safety population. df = degrees of freedom; IV = inverse variance; M-H = Mantel-Haenszel.

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