Antibiotic Cayston Effective for Some Bronchiectasis Symptoms but Not All, Study Says

Antibiotic Cayston Effective for Some Bronchiectasis Symptoms but Not All, Study Says
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Treatment with the inhaled antibiotic Cayston (aztreonam lysine) reduced cough and sputum production, but was not effective against breathlessness and wheezing in people with bronchiectasis, according to an analysis of two clinical trials.

Based on these findings, the researchers recommended inhaled antibiotics for patients with daily cough producing discolored sputum but not for those with significant wheezing and breathlessness. 

The study, “Inhaled Aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post-hoc analysis of the AIR-BX studies,” was published in the European Respiratory Journal.

Bacterial infections in people with bronchiectasis are linked to a heightened risk of disease exacerbation — an immediate increase in cough and sputum (a mixture of saliva and mucus from the lungs), along with breathlessness and fatigue.

Standard treatment is to prescribe inhaled antibiotics that deliver high concentrations of the medicine directly to the site of infection. 

Despite the success in lowering bacteria numbers in clinical practice, a large-scale analysis of 16 trials showed that inhaled antibiotics only modestly decreased the number of exacerbations and there was no clinically significant alleviation in symptoms

The reason for this disparity may be related to limitations in the quality of life bronchiectasis questionnaire (QOL-B), which is the only disease-specific tool tested in multiple clinical studies. QOL-B assesses lung symptoms by asking questions about cough, congestion, sputum production and color, shortness of breath, wheezing, chest pain, and nighttime cough. 

Despite reported benefits against cough and sputum production, inhaled antibiotics may not have a positive impact on other symptoms. 

To get a better understanding of how inhaled antibiotics affect each lung symptom, researchers at the University of Dundee in Scotland and their collaborators analyzed two identical Phase 3 trials — AIR-BX1 (NCT01313624) and AIR-BX2 (NCT01314716) — that had tested Gilead Sciences‘ inhaled antibiotic Cayston in bronchiectasis patients. 

Data from 440 patients, at an average age of 64, were included in the analysis. They had received either 75 mg of Cayston or a placebo three times daily; 70% of them did not experience an exacerbation during the study. In both Gilead-sponsored trials, treatment was given in two cycles of eight weeks each, with four weeks on the antibiotic and four weeks off.

The primary goal was a change in respiratory symptoms at the end of the first on-treatment period (week four), as measured by the QOL-B. A secondary goal was to measure time to first exacerbation by 16 weeks. 

Results at four weeks showed that, compared with the placebo, treatment with Cayston led to a significant reduction in daily cough (20%), sputum production (25.7%), and sputum purulence (25.2%) — the presence of yellow or green pus in sputum. Similar benefits were shown across the entire trial duration for cough, sputum production, and sputum purulence.

While there were no significant changes in congestion or cough at night, those treated with the inhaled antibiotic reported worse shortness of breath, wheezing, and chest pain. However, these differences were not statistically significant.

Further analysis found that those reporting “a lot” or a “moderate amount” of sputum production at baseline showed a significant improvement with treatment. Those who reported  “a little” or “not at all” sputum production had no benefit. The results were similar for sputum color. 

In the original AIR-BX analysis, the time to first exacerbation for patients treated with Cayston tended to be shorter, and they also had a higher number of exacerbations, which was attributed to the adverse effects of inhaling a medicine. 

However, in this analysis, participants with significantly less congestion, cough, sputum color, and nighttime cough at the start of the study experienced a shorter time to first exacerbation. In contrast, those with higher baseline wheezing had their first exacerbation sooner, although this result was not statistically significant. 

“In conclusion, our results suggest [Cayston] improves cough, sputum production and sputum colour but does not significantly affect other symptoms in bronchiectasis,” the scientists wrote. “Inhaled antibiotic treatment may be most effective in patients with daily cough and producing discoloured sputum, and clinicians may wish to avoid treatment in patients with significant breathlessness and wheeze.”

“Future trials should consider enrolling patients with a higher burden of [lung] symptoms and develop symptom evaluation tools which give greater weight to these symptoms,” they added.

Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
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