Semin Respir Crit Care Med 2021; 42(04): 606-615
DOI: 10.1055/s-0041-1730945
Review Article

Long-Term Antibiotics in Bronchiectasis

Guillermo Suarez-Cuartin
1   Department of Respiratory Medicine, Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
,
Marta Hernandez-Argudo
1   Department of Respiratory Medicine, Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
,
Lidia Perea
2   Department of Respiratory Medicine, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERES, Barcelona, Spain
,
Oriol Sibila
2   Department of Respiratory Medicine, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERES, Barcelona, Spain
› Author Affiliations

Abstract

A significant proportion of bronchiectasis patients are chronically infected by potentially pathogenic microorganisms which may lead to frequent exacerbations and worse clinical outcomes. Current bronchiectasis guidelines recommend long-term inhaled antibiotics and/or oral macrolides as a part of patient management. In recent years, an increasing amount of evidence assessing the impact of these treatments on patient outcomes has been collected. Inhaled antibiotics have demonstrated significant improvements in sputum bacterial load, but their impact on patient quality of life, lung function, and exacerbation rate has not been consistent across trials. In this regard, recent post hoc analyses of inhaled antibiotics trials in bronchiectasis patients have shown that sputum bacterial load may be a key biomarker to predict treatment response in these patients. Oral macrolides, on the other hand, have proven to reduce exacerbation frequency and improve quality of life, but potential drug-related adverse effects and the increase in bacterial resistance are relevant. This review aims to summarize current important evidence for long-term antibiotic treatment in bronchiectasis patients.



Publication History

Article published online:
14 July 2021

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  • References

  • 1 Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet 2018; 392 (10150): 880-890
  • 2 Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A comprehensive analysis of the impact of Pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann Am Thorac Soc 2015; 12 (11) 1602-1611
  • 3 Tunney MM, Einarsson GG, Wei L. et al. Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am J Respir Crit Care Med 2013; 187 (10) 1118-1126
  • 4 Angrill J, Agustí C, de Celis R. et al. Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors. Thorax 2002; 57 (01) 15-19
  • 5 Chalmers JD, Aliberti S, Filonenko A. et al. Characterization of the “frequent exacerbator phenotype” in bronchiectasis. Am J Respir Crit Care Med 2018; 197 (11) 1410-1420
  • 6 Sibila O, Perea L, Cantó E. et al. Antimicrobial peptides, disease severity and exacerbations in bronchiectasis. Thorax 2019; 74 (09) 835-842
  • 7 Perea L, Cantó E, Suarez-Cuartin G. et al. A cluster analysis of bronchiectasis patients based on the airway immune profile. Chest 2020; S0012-3692 (20)35156-4 DOI: 10.1016/j.chest.2020.11.011.
  • 8 Martínez-García MA, Soler-Cataluña J-J, Perpiñá-Tordera M, Román-Sánchez P, Soriano J. Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis. Chest 2007; 132 (05) 1565-1572
  • 9 Davies G, Wells AU, Doffman S, Watanabe S, Wilson R. The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis. Eur Respir J 2006; 28 (05) 974-979
  • 10 Araújo D, Shteinberg M, Aliberti S. et al. The independent contribution of Pseudomonas aeruginosa infection to long-term clinical outcomes in bronchiectasis. Eur Respir J 2018; 51 (02) 1701953
  • 11 Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur Respir J 2014; 44 (02) 382-393
  • 12 Laska IF, Crichton ML, Shoemark A, Chalmers JD. The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis. Lancet Respir Med 2019; 7 (10) 855-869
  • 13 Polverino E, Goeminne PC, McDonnell MJ. et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J 2017; 50 (03) 1700629
  • 14 Martínez-García MÁ, Máiz L, Olveira C. et al. Spanish guidelines on treatment of bronchiectasis in adults. [in Spanish]. Arch Bronconeumol 2018; 54 (02) 88-98
  • 15 Hill AT, Sullivan AL, Chalmers JD. et al. British Thoracic Society Guideline for bronchiectasis in adults. Thorax 2019; 74 (Suppl. 01) 1-69
  • 16 Orriols R, Roig J, Ferrer J. et al. Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa . Respir Med 1999; 93 (07) 476-480
  • 17 Barker AF, Couch L, Fiel SB. et al. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 2000; 162 (2, Pt 1): 481-485
  • 18 Couch LA. Treatment with tobramycin solution for inhalation in bronchiectasis patients with Pseudomonas aeruginosa . Chest 2001; 120 (3, Suppl): 114S-117S
  • 19 Scheinberg P, Shore E. A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis. Chest 2005; 127 (04) 1420-1426
  • 20 Drobnic ME, Suñé P, Montoro JB, Ferrer A, Orriols R. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa . Ann Pharmacother 2005; 39 (01) 39-44
  • 21 Loebinger MR, Polverino E, Chalmers JD. et al; iBEST-1 Trial Team. Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study. Eur Respir J 2021; 57 (01) 2001451
  • 22 Insmed. Safety and Tolerability Study of 2 Dose Level of ArikayceTM in Patients with Bronchiectasis and Chronic Infection Due to Pseudomonas Aeruginosa. - Study Results - ClinicalTrials.gov. Accessed January 17, 2021 at: https://clinicaltrials.gov/ct2/show/results/NCT00775138
  • 23 Murray MP, Govan JRW, Doherty CJ. et al. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2011; 183 (04) 491-499
  • 24 Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2012; 186 (07) 657-665
  • 25 Sibila O. Reducing Pseudomonas sputum density in bronchiectasis. Eur Respir J 2021; 57 (01) 2003390
  • 26 Barker AF, O'Donnell AE, Flume P. et al. Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med 2014; 2 (09) 738-749
  • 27 Sibila O, Laserna E, Shoemark A. et al. Airway bacterial load and inhaled antibiotic response in bronchiectasis. Am J Respir Crit Care Med 2019; 200 (01) 33-41
  • 28 Crichton ML, Lonergan M, Barker AF. et al. Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies. Eur Respir J 2020; 56 (01) 2000608
  • 29 Serisier DJ, Bilton D, De Soyza A. et al; ORBIT-2 Investigators. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. Thorax 2013; 68 (09) 812-817
  • 30 Wilson R, Welte T, Polverino E. et al. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J 2013; 41 (05) 1107-1115
  • 31 De Soyza A, Aksamit T, Bandel TJ. et al. RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis. Eur Respir J 2018; 51 (01) 1702052
  • 32 Aksamit T, De Soyza A, Bandel T-J. et al. RESPIRE 2: a phase III placebo-controlled randomised trial of ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis. Eur Respir J 2018; 51 (01) 1702053
  • 33 Haworth CS, Bilton D, Chalmers JD. et al. Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. Lancet Respir Med 2019; 7 (03) 213-226
  • 34 Chalmers JD, Cipolla D, Thompson B. et al. Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies. Eur Respir J 2020; 56 (04) 2000110
  • 35 Haworth CS, Foweraker JE, Wilkinson P, Kenyon RF, Bilton D. Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 2014; 189 (08) 975-982
  • 36 Wong C, Jayaram L, Karalus N. et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 2012; 380 (9842): 660-667
  • 37 Altenburg J, de Graaff CS, Stienstra Y. et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA 2013; 309 (12) 1251-1259
  • 38 Serisier DJ, Martin ML, McGuckin MA. et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA 2013; 309 (12) 1260-1267
  • 39 Chalmers JD, Boersma W, Lonergan M. et al. Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis. Lancet Respir Med 2019; 7 (10) 845-854
  • 40 Kelly C, Chalmers JD, Crossingham I. et al. Macrolide antibiotics for bronchiectasis. Cochrane Database Syst Rev 2018; 3 (03) CD012406
  • 41 PROLONGED antibiotic treatment of severe bronchiectasis; a report by a subcommittee of the Antibiotics Clinical Trials (non-tuberculous) Committee of the Medical Research Council. BMJ 1957; 2 (5039): 255-259
  • 42 Currie DC, Garbett ND, Chan KL. et al. Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis. Q J Med 1990; 76 (280) 799-816
  • 43 Rayner CFJ, Tillotson G, Cole PJ, Wilson R. Efficacy and safety of long-term ciprofloxacin in the management of severe bronchiectasis. J Antimicrob Chemother 1994; 34 (01) 149-156
  • 44 Hill AT, Welham SA, Sullivan AL, Loebinger MR. Updated BTS Adult Bronchiectasis Guideline 2018: a multidisciplinary approach to comprehensive care. Thorax 2019; 74 (01) 1-3
  • 45 Pomares X, Montón C, Bullich M. et al. Clinical and safety outcomes of long-term azithromycin therapy in severe COPD beyond the first year of treatment. Chest 2018; 153 (05) 1125-1133