Inhaled-IV Antibiotic Combo May Better Treat Acute Flares Than IV-only Mix

When given alongside the antibiotic Colistin (colistimethate), Cayston (aztreonam lysine), an inhaled antibiotic specifically targeting Pseudomonas aeruginosa, was superior to standard intravenous antibiotics at improving lung function and life quality among adults with cystic fibrosis (CF) and lung infections due to P. aeruginosa during an acute flare, a single-site U.K. trial reports.

According to its investigators, these findings from a support further testing in patients of inhaled antibiotics at managing CF acute exacerbations.

Trial data were detailed in the study, “The clinical and microbiological utility of inhaled aztreonam lysine for the treatment of acute pulmonary exacerbations of cystic fibrosis: An open-label randomised crossover study (AZTEC-CF),” published in the Journal of Cystic Fibrosis.

Acute disease flares, or exacerbations, are frequent in people with CF and diminish lung health and overall quality of life.

Current U.K. guidelines recommend that CF exacerbations be managed with a combination of two intravenous (IV) antibiotics given over 10 to 14 days. Yet, study researchers noted, such prolonged antibiotic use can cause side effects, and may affect the lung microbiome — the population of microbes living in the lungs.

Several inhaled antibiotics have been found to be effective at treating lung infections caused by the P. aeruginosa bacteria in CF patients. However, little is known regarding their potential usefulness at managing acute flares.

Investigators at an adult CF care center in Liverpool conducted a Phase 4 trial (NCT02894684) to assess if a combination of Cayston (marketed by Gilead) and Colistin, an IV antibiotic often used as a last resort to treat bacterial infections, might be superior to a standard IV antibiotic combination in treating patients with acute exacerbations.

Their open-label, randomized, and crossover study, called AZTEC-CF, enrolled 16 adults (median age, 29.5) with CF and lung infections caused by P. aeruginosa.

Participants were followed over the course of two acute flares. During the first, they were randomly assigned to be treated either with inhaled Cayston and intravenous Colistin, or with standard IV antibiotic care, for 14 days.

The 12 patients treated for a second flare (two left the study and two did not have a further exacerbation) changed treatment groups. Those previously given the Cayston-Colistin combination crossed to the standard IV antibiotic combo, while patients on that standard of care moved to the inhaled-IV regimen. Both groups were again treated for 14 days.

The study’s primary goal was changes in patients’ lung function, based on forced expiratory volume in one second (FEV1) — a parameter that measures the total amount of air exhaled in one second after a deep breath. Changes in patients’ quality of life, bacterial load, and lung microbiota composition were also assessed.

For their analyses, researchers combined data from those patients who underwent each of the two, 14-day treatment regimens. Results showed that patients receiving Cayston together with Colistin saw their lung function improve — a mean FEV1 increase of 4.6% — compared with those on standard IV antibiotics.

“A poor FEV1 response during treatment for an exacerbation is associated with failure to recover pre-exacerbation lung function and occurs in approximately 25% of exacerbations. In that regard, the continued improvements observed in the second week of treatment with AZLI+IV [Cayston plus Colistin] may be of particular clinical significance,” the scientists wrote.

Although both treatment courses led to improvements in patients’ quality of life (under the Cystic Fibrosis Revised Questionnaire, or CFQ-R), investigators found that a higher percentage of those treated with the Cayston-Colistin combo experienced clinically meaningful improvements in life quality (83.3%), compared with those given  intravenous antibiotics (43.8%).

IV antibiotic treatment was also found to change the composition of patients’ lung microbiome, while no significant microbiome alterations were seen with Cayston plus Colistin treatment.

Yet, no differences were seen between these two regimens regarding the amount of bacteria in patients’ sputum samples (mucus expelled by coughing), or on other blood parameters analyzed, including white blood cell counts.

The incidence of side effects was identical between groups, with half of the patients in each reporting at least one side effect. The most common, reported for 25% in each group, was a need for antibiotic treatment that stretched beyond 14 days. Overall, both regimens were “well-tolerated,” the researchers wrote.

“In adults with CF and P. aeruginosa infection experiencing an acute pulmonary exacerbation, [Cayston and Colistin] improved lung function and quality of life compared to the current standard treatment. These findings support the need for larger definitive trials of inhaled antibiotics in the acute setting,” the researchers wrote.