Azithromycin at chronic PSA

Question

Dear expert team,
my 11-year-old son is chronically colonized with Pseudomonas aeruginosa (PSA) for one year (FEV1 98%). He inhales 2x colistin and 1x DNAse.
We consider, in case his lung function should worsen, to try azithromycin.
- how is the effect of this antibiotic on the PSA ? (by which mechanisms)
- how compatible is it?
- which dosage and time of taking it would be optimal for 40 kg and 1.49 cm?
Many thanks for your assesesment!

Answer

Hello,
the idea of giving macrolides, to which belong also Azithromycin, to patients with CF comes from a japanese study, in which a positive effect could have been shown under the treatment with Erythromycin at diffuse panbronchiolitis, an illness which has many similarities with CF. In CF, a similar positive effect could have been shown in several studies with the macrolide Azithromycin, some studies showed an improvment of the lung function, less admissions to hospital, a reduced need for antibiotic therapy and decreasing inflammatory markers; in addition some studies were able to show a decrease of the number of exacerbations (worsenings of infections) and an improvment of the quality of life parameters. The detailed mechanism of action of the macrolides in humans with CF and chronical colonization with Pseudomonas aeruginosa is not clarified totally, however anti-inflammatory and anti-bacterial effects are suspected as well as immunmodulating effects and protective effects on the epithelial cells.
The duration of therapy has been 3-12 months in the above mentioned studies. The positive effects seems only to occur after several weeks, whereas after cessation the effect disappears after one month. About the recommendable duration and administration there is plenty of discussion.
Assumed that there is no allergy against macrolides, it is recommended in patients under 18 years and 40 kg body weight to take daily an oral dosage of 250mg Azithromycin, alternatively once a week 1000mg. The drug is independent of the modus of administration mostly well tolerated, gastro-intestinal complaints however, have been reported. In most cases this oral therapy is begun after a cylce of i.v. administered antibiotics.
Yours sincerely,
Prof.Dr.H.Ellemunter

09.07.2009