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Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis

  • Sofia Tejada
    Correspondence
    Corresponding author at: Vall d'Hebron Institut de Recerca, Ps Vall d'Hebron 119 AMI-14th floor. 08035 Barcelona, Spain
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

    Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain
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  • Laura Campogiani
    Affiliations
    Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy
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  • Candela Solé-Lleonart
    Affiliations
    Intensive Care Unit, Hospital Universitari de Vic, Barcelona, Spain
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  • Aroa Gómez
    Affiliations
    Department of Donor & Transplant Coordination, Vall d'Hebron University Hospital, Barcelona, Spain
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  • Miguel Gallego
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

    Respiratory Department, Parc Taulí University Hospital, Barcelona, Spain
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  • Monserrat Vendrell
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

    Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain

    Respiratory Department, Dr. Josep Trueta University Hospital, Girona, Spain

    Insitut d'Investigació Biomèdica de Girona (IDIBGI), Universitat de Girona, Girona, Spain
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  • Joan B. Soriano
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

    Hospital Universitario La Princesa, Universidad Autónoma de Madrid, Madrid, Spain
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  • Jordi Rello
    Affiliations
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

    Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain

    Clinical Research in the ICU, Anesthesia Department, CHU Nimes, Universite de Nimes-Montpellier, France
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      Highlights

      • IA use in stable NCFB had microbiologic benefit with 10% reduction of exacerbations.
      • IA therapy in NCFB increased antimicrobial resistance, with NNT of 6.
      • Minimal benefit in terms of patient-centered outcomes was documented.
      • Further research is required in high inflammatory phenotypes and alternative strategies.

      Abstract

      Background

      Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations.

      Methods

      We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154.

      Results

      Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70–5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81–18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28–1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82–0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV1, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35–3.27) at the end of therapy, with a number needed to treat of 6.

      Conclusions

      IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.

      Keywords

      Abbreviations:

      AE (Adverse Events), IA (Inhaled Antibiotics), NCFB (Non-Cystic Fibrosis Bronchiectasis), NTM (Non-Tuberculosis mycobacterium), OR (Odd Ratio), RCT (Randomized Controlled Trials), RR (Risk Ratio), SAE (Serious Adverse Events), SRMA (Systematic Review and Meta-analysis)
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