Antibiotic Plus Vitamin E Given Stable CF Patients Fails to Lower Oxidative Stress Levels in Pilot Study

Treating cystic fibrosis (CF) patients with the antibiotic azithromycin in addition to vitamin E supplements did not change their oxidative stress status in a pilot study, researchers report.

These results were published in the journal Frontiers in Pharmacology, in the article “Metabolomic Analysis by Nuclear Magnetic Resonance Spectroscopy as a New Approach to Understanding Inflammation and Monitoring of Pharmacological Therapy in Children and Young Adults With Cystic Fibrosis.”

Studies in mice models of CF have found that azithromycin (brand name Zithromax, by Pfizer) could reduce the levels of inflammatory biomarkers in the animals’ blood, and support its antioxidant mechanisms. While its anti-inflammatory activity has already been demonstrated in CF patients, little is known about its potential antioxidant effects.

To further evaluate azithromycin’s properties, Italian researchers conducted a pilot, proof-of-concept, clinical study.

A total of 45 patients with stable CF, ages 6 and 20, were randomized to receive daily oral vitamin E alone or in combination with 250 or 500 mg of azithromycin, depending on body weight, for eight weeks.

The team assessed the levels of 15-F2t-Isoprostane, a reliable biomarker of oxidative stress, in the patients’ blood and exhaled breath condensate (EBC; a non-invasive technique for sampling airway secretions). Researchers also looked for the presence of other biological compounds (metabolites) in these samples.

Results showed that azithromycin as an add-on treatment did not trigger changes in 15-F2t-Isoprostane compared to baseline levels, or compared to vitamin E alone, in both EBC and blood samples. No changes were seen in the levels of C-reactive protein, a biomarker of inflammation, or in lung function during the study. The combo treatment’s lack of efficacy in improving lung function might be due to the short treatment period and “the fact that less than 50% of CF patients included in our study had chronic P. aeruginosa infection,” they wrote.

But analysis of other metabolites in EBC samples showed possible therapy effects, although they are not yet understood.

Two weeks after the study’s end, researchers found that the combo treatment promoted different patterns of metabolite levels, namely those of ethanol, saturated fatty acids, acetate, acetone, and methanol.

Further studies are needed to fully understand the biological and therapeutic implications of these metabolite changes seen in CF patients, the researchers noted.

“Our study was unable to show antioxidant effect of azithromycin as add-on treatment with … oral vitamin E,” the researchers wrote. “But its suspension is associated with EBC metabolic profiles that are different from those observed after vitamin E suspension.”

These preliminary results suggest that EBC metabolomics (metabolic profile) “might be used for assessing the effects of pharmacological treatment suspension in stable CF patients,” they suggested.