Cystic fibrosis

OPTIMIZE trial: long term azithromycin preserves lung function in CF children


The longest randomised controlled trial of azithromycin treatment in children with cystic fibrosis has shown a 44% reduction in exacerbations over 18 months.

The OPTIMIZE trial conducted in 221 US children with CF aged 6 months-18 years with recent Pseudomanas aeruginosa acquisition also found that regular treatment with oral azithromycin appears safe when the macrolide is used in addition to conventional tobramycin treatment.

In the study, children with CF were randomised to oral azithromycin three times weekly or placebo in addition to tobramycin inhalation solution.

After 18 months of follow up the number of children experiencing an exacerbation was 43/110 (39.1%) in the azithromycin group and 58/111 (52.3%) in the placebo group (Hazard Ratio  0.56). The largest benefit (62% risk reduction) was seen in younger children under three years of age who had highest rates of treatment adherence.

Published in the American Journal of Respiratory and Critical Care Medicine the findings also show that childrens’ weight increased by an average of 1.27kg in those treated with azithromycin compared to the control group.

Extended use of azithromycin was not associated with any increase in risk of hearing loss or prolongation of QTc interval. There was also no difference between groups in Pseudomonas eradication or re-aquisition rates, suggesting that concomitant azithromycin does not interfere with the efficacy of tobramycin, the study authors note.

They say it is disappointing that azithromycin did not appear to break the cycle of Pseudomonas recurrence, but the findings are significant because they represent the longest duration of effectiveness of azithromycin in reducing exacerbations in patients with CF. The macrolide is believed to act via an anti-inflammatory action, but more work is needed to elucidate inflammatory markers to conform this, they add.

“Given the association between exacerbation risk and morbidity over the lifetime of individuals with CF, azithromycin may be a therapeutic option for children with CF and early Pseudomonas aeruginosa infection,” they conclude.

The findings now raise the question of whether long term azithromycin therapy should be offered to children with CF, according to an accompanying commentary co-authored by Australian paediatric respiratory physician Dr Andre Schultz.

Concerns about the development of macrolide resistance should be weighed against the fact that other antibiotics are available to treat infections such as H. influenzae and S. aureus, writes Dr Schultze, who is Director of Cystic Fibrosis at Perth Children’s Hospital.

However the potential acquisition of non-tuberculous mycobacterium – especially M. absecessus – remains an unaddressed a concern for children in tropical areas of Australia such as Queensland, the commentary notes.

“Hence, while the evidence in favour of long term azithromycin use in children with CF is accumulating, concerns still remain. Long term azithromycin is perhaps best positioned for use in younger children where the risk of M. abscessus infection is low,” he writes with co-author Professor Peter Sly, of the Queensland University Child Health Research Centre.

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