Antimicrobial resistance (AMR) represents a serious and growing threat to human and animal health worldwide. In the EU alone, AMR is responsible for some 25 000 deaths every year, and the annual treatment and social costs have been estimated at €1.5 billion. Meanwhile, new forms of resistance continue to develop and spread, leaving clinicians with few weapons to bring infections under control. Yet despite the recognised need for new antibiotics, the reality is that only two new classes of antibiotics have been brought to the market in the last three decades.
A vulnerable group
Patients with cystic fibrosis (CF) and bronchiectasis (BE) are at particular risk of infection. CF is a common inherited disease that affects around 36 000 people in the EU. CF patients face regular respiratory infections; 60% of adult patients have lung infections caused by difficult to treat bacteria such as Pseudomonas aeruginosa, and respiratory failure is the cause of death for 95% of CF patients. Inhaled antibiotics have helped to both improve CF patients’ quality of life and extend their life expectancy.
BE refers to a group of diseases in which the airways become damaged and scarred. It is more common among the elderly, affecting 3 in 1 000 among the over 75s. BE patients experience similar symptoms to CF, including regular respiratory infections, often with Pseudomonas aeruginosa. So far, no inhaled antibiotics have been approved for use in BE patients, although in practice doctors often treat BE patients with antibiotics licensed for use in CF.
Today, the number of inhaled antibiotics available for these vulnerable patients remain limited and infections in both CF and BE patients are increasingly resistant to these life-saving medicines. The costs of carrying out clinical trials for new antibiotics for CF and BE patients are particularly high due to the relatively small number of patients affected.
Towards new treatments for cystic fibrosis and bronchiectasis
iABC will advance the development of two inhaled antimicrobials. BAL30072 is a novel antibiotic that is effective against a range of bacterial infections. The project will develop a version of the antibiotic that can be inhaled by patients with CF and BE. Studies will probe the safety of the inhaled antibiotic and determine the ideal dose. The project will also investigate the appropriate dose of tobramycin inhalation powder (TIP) in treatment of lung infections in BE patients and how safe and effective this dose is in these patients. TIP is currently only licensed for use in CF patients.
More broadly, the programme will undertake a number of activities designed to facilitate future research into and clinical trials involving CF and BE. For example, part of the project is devoted to setting up an EU-wide registry of BE patients that would align new and existing national registries and facilitate the gathering of data on BE in Europe. This will aid in the identification of research needs, make it easier to identify patients who could be included in clinical trials, and guide the development of European guidelines for the management of BE. iABC will ensure that the BE registry will remain viable after the end of the project.
Another project goal is to identify measures that could be used in clinical trials to assess the effectiveness of a medicine. These will include new ways of more accurately assessing lung function, DNA fingerprinting of bacteria, measurement of inflammatory biomarkers in the sputum and scoring CT (computed tomography) scans of the chest. The project will also study the nature and level of microbes found in the sputum.
New hope for patients
Just a few decades ago, most CF patients died in early childhood. Thanks to antibiotics, CF patients born today can expect to reach early middle age. However, this progress is threatened by the rise of antimicrobial resistance. The iABC project represents an important contribution to efforts to counter this threat.