Background: Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the United States or Europe for the treatment of bronchiectasis not related to cystic fibrosis. Pseudomonas aeruginosa infection is common in patients with bronchiectasis, contributing to a cycle of progressive inflammation, exacerbations, and airway remodelling. Objective: The aim of the current study was to identify and evaluate published studies of inhaled tobramycin solution or powder in patients with bronchiectasis and P. aeruginosa infection not associated with cystic fibrosis. Methods: A literature review was conducted utilising the PubMed and Cochrane databases. Studies published in the English language that reported safety and/or efficacy outcomes of inhaled tobramycin either alone or in combination with other antibiotics were included. Results: Seven clinical trials published between 1999 and 2021 were identified that met inclusion criteria. Inhaled tobramycin therapy was effective in reducing P. aeruginosa microbial density in the sputum of patients with bronchiectasis. Several studies demonstrated favourable impacts on hospitalisations, number and severity of exacerbations, and symptoms. Other studies were underpowered for these clinical outcomes or were exploratory in nature. Although tobramycin was generally well tolerated, some evidence of treatment-associated wheezing was reported. Conclusions: In patients with bronchiectasis and chronic P. aeruginosa infection, inhaled tobramycin was effective in reducing the density of bacteria in sputum, which may be associated with additional clinical benefits. Definitive phase 3 trials of inhaled tobramycin in patients with bronchiectasis are indicated to determine clinical efficacy and long-term safety.
Bibliographical noteFunding Information:
Technical, editorial, and medical writing assistance were provided under the direction of the authors by Strategix, an affiliate of The Lynx Group, LLC. Funding for this support was provided by Viatris Inc.
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J Stuart Elborn has received grant funding from Novartis AG to develop inhaled tobramycin as part of the Innovative Medicines Initiative of the Seventh Framework Programme funded by the European Commission. He has also received payment for an educational talk at the European Cystic Fibrosis Society. Francesco Blasi reports grants and personal fees from AstraZeneca PLC, grants from Bayer AG, grants and personal fees from Chiesi Farmaceutici SpA, grants and personal fees from GlaxoSmithKline PLC, personal fees from Grifols SA, personal fees from Laboratori Guidotti SpA, personal fees from Insmed, Inc., grants and personal fees from the Menarini Group, personal fees from Novartis International AG, grants and personal fees from Pfizer Inc., personal fees from Zambon Pharma, personal fees from Vertex Pharmaceuticals, Inc., personal fees from Viatris Inc., and personal fees from Sanofi Genzyme. Charles S Haworth has received consultancy, advisory board or speaker fees from: Aradigm Corp, Chiesi Farmaceutici SpA, Gilead Sciences, Inc., GlaxoSmithKline PLC, Grifols SA, Insmed, Inc., Janssen Pharmaceuticals, Meiji Seika Pharma Co, Ltd, Mylan NV, Novartis International AG, Profile Pharma Limited, Shionogi Inc., Teva Pharmaceutical Industries Ltd, Vertex Pharmaceuticals, Inc., and Zambon. Manfred Ballmann received fees as an advisory board member form Novartis International AG and Gilead Sciences, Inc., and lectures fees from Chiesi Farmaceutici SpA. Harm AWM Tiddens has received grant funding or consultancy fees from Chiesi Farmaceutici Spa, Insmed, Inc., Novartis International AG, Thirona, and Vertex Pharmaceuticals, Inc. Marlene Murris-Espin has received advisory board and non-financial support from Insmed, Inc. and Zambon. James D Chalmers has received grant funding or consultancy fees from AstraZeneca PLC, Chiesi Farmaceutici SpA, Gilead Sciences, Inc., GlaxoSmithKline PLC, Grifols SA, Insmed, Inc., Novartis International AG, and Zambon. André Cantin has received honoraria from Vertex Pharmaceuticals (Canada) Inc. for the preparation of educational material that is outside the scope of the submitted work.