Antimicrobial treatment of non-cystic fibrosis bronchiectasis

Abstract

Bronchiectasis unrelated to cystic fibrosis is characterized by chronic wet or productive cough, recurrent exacerbations and irreversible bronchial dilatation. After antibiotics and vaccines became available and living standards in affluent countries improved, its resulting reduced prevalence meant bronchiectasis was considered an ‘orphan disease’. This perception has changed recently with increasing use of CT scans to diagnose bronchiectasis, including in those with severe chronic obstructive pulmonary disease or ‘difficult to control’ asthma, and adds to its already known importance in non-affluent countries and disadvantaged Indigenous communities. Following years of neglect, there is renewed interest in identifying the pathogenetic mechanisms of bronchiectasis, including the role of infection, and conducting clinical trials. This is providing much needed evidence to guide antimicrobial therapy, which has relied previously upon extrapolating treatments used in cystic fibrosis and chronic obstructive pulmonary disease. While many knowledge gaps and management challenges remain, the future is improving for patients with bronchiectasis.

Keywords::

• amikacin
• azithromycin
• bronchiectasis
• colistin
• Haemophilus influenzae
• microbiota
• non-tuberculous mycobacteria
• Pseudomonas aeruginosa
• respiratory viruses
• tobramycin

Financial & competing interests disclosure

The paper was not directly funded AC salary is supported by a NHMRC practitioner fellowship (grant 1058213) and work around bronchiectasis in children is supported by a NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children (grant number 1040830). SC Bell is supported by a Queensland Health, Health Research Fellowship (QCOS013795). K Grimwood has served as a member of an Advisory Board to GlaxoSmithKline on pneumococcal conjugate vaccines. SC Bell has served as a member of an Advisory Board to Vertex, Rempex and Novartis, and received travel support to attend and speak at symposia by Gilead to attend ECFC (Novartis). SC Bell is also lead investigator on (site) trials sponsored by Pharmaxis, Rempex and Vertex. AB Chang has received an investigator-driven grant from GlaxoSmithKline to examine the effect of a pneumococcal vaccine on the BAL of children. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Bronchiectasis unrelated to cystic fibrosis is an important contributor to morbidity and mortality from chronic pulmonary disorders worldwide. Although historically treatments were extrapolated from successful therapies in cystic fibrosis or chronic obstructive pulmonary disease, more recent clinical trials have shown that these treatments can be poorly tolerated or even deleterious when used for patients with bronchiectasis.

• Despite many causes, the final common pathway involves airway injury and impaired airway clearance following a cycle of infection, inflammation and tissue remodeling. Antibiotics seek to break this cycle by reducing bacterial load and, in so doing, reducing exacerbations, improving quality of life and preventing pulmonary decline.

• Depending upon severity, oral or parenteral antibiotics should be commenced promptly for acute exacerbations and guided initially by prior culture results or, if these results are unavailable, by the most likely pathogens and their local susceptibility patterns. Subsequent therapy is determined by clinical response and respiratory culture results.

• When Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus or non-tuberculous mycobacteria are detected (both for the first time or recurring isolates), advice should be sought from respiratory, microbiology and infectious diseases experts for consideration of treatment, including eradication therapy.

• Long-term suppressive antibiotic therapy is an option when recurrent exacerbations are frequent (≥3 per year) and impacting upon quality of life. Macrolides (or other oral antibiotics) can be given for therapeutic trials of 12–24 months. Because of balancing clinical benefit with risks of rare, but severe adverse events, and developing antibiotic resistance, specialist respiratory and infectious disease advice should be sought initially. When prescribing long-term macrolide antibiotics, it is important to exclude an underlying non-tuberculous mycobacteria infection, check for risk factors for QTc interval prolongation and ensure normal electrocardiograms and hearing for age.

• Long-term inhaled antibiotics are an alternative to oral agents, but they need to be individualized as the evidence to date has relied mostly upon short-term trials, where clinical benefits have been variable and respiratory adverse events common.

• Future research will provide a greater understanding of the pathobiology of bronchiectasis allowing novel therapies to be developed. Simple and safe assessment techniques are required with robust measures of lung structure and function and validated clinical severity tools in various patient populations. The reasons for suboptimal treatment adherence also need investigation.

• Studies are required to evaluate the pathogenic role of the resident lung microbiome and to determine optimal long-term antibiotic regimens.