Although most children with cystic fibrosis (CF) who received azithromycin recovered lung function following intravenous tobramycin treatment for pulmonary exacerbations, these children also had smaller relative improvements compared with those not on azithromycin when baseline forced expiratory volume in 1 second (FEV1) was taken into account.

The result of the study, published in Annals of the American Thoracic Society, indicate a need for randomized controlled trials comparing antibiotic therapies.

Researchers designed the study to identify associations between oral azithromycin use and lung function response to intravenous tobramycin treatment in pediatric patients with CF and chronic Pseudomonas aeruginosa infections being treated for pulmonary exacerbations. Treatment response was defined as the change in FEV1 from the start of treatment to end of treatment as well as FEV1 recovery to ≥90% of baseline (defined as best FEV1 measured in the previous 6 months before the exacerbation). Treatment response of azithromycin users was compared with the treatment response of azithromycin nonusers using marginal structural modeling that accounted for baseline FEV1 as both a confounder and mediator.

Of the 33 patients with 67 exacerbations, 69% of azithromycin users returned to ≥90% of baseline FEV1 compared with 61% of azithromycin nonusers. However, the azithromycin users had worse baseline FEV1 compared with nonusers, making the relative FEV1 improvement 9.5% lower in azithromycin users compared with azithromycin nonusers (95% CI, –18.7 to –0.3).

Limitations included a small sample size due to strict inclusion criteria, only pediatric participants, and an inability to measure lifetime exposure to tobramycin.

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“This retrospective study is limited in its ability to definitively answer the question as to whether CF patients on chronic oral azithromycin have a poorer response to IV tobramycin treatment of [pulmonary exacerbations],” the researchers wrote. “Randomized controlled trials of IV tobramycin compared to alternative antibiotic therapy in CF patients on chronic oral azithromycin are thus needed to prospectively address this question, as is currently being done with the TEACH trial, testing the effect of adding chronic azithromycin to inhaled tobramycin (NCT02677701).”

Reference

Klingel M, Stanojevic S, Tullis E, Ratjen F, Waters V. The effect of oral azithromycin on the response to pulmonary exacerbations treated with intravenous tobramycin in children with cystic fibrosis [published online March 15, 2019]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201811-774OC