Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. People with cystic fibrosis are particularly prone to chest infections caused by bacteria that are hard to treat, but one possible treatment is a class of antibiotic known as the macrolides. There's been a Cochrane Review of this since 2003 and the fourth update was published in February 2024. Here's Kevin Southern from Alder Hey Children's Hospital in the UK, who is one of its authors and an Editor for the Cochrane Cystic Fibrosis Group, to tell us more.

Kevin: Cystic fibrosis, or CF, is a life-limiting genetic condition which affects around 90,000 people worldwide. It causes sticky mucus to build up in several organs in the body, which, in the airways, can lead to recurring chest infections. Two different bacteria that commonly cause these chest infections are Staphylococcus aureus and Pseudomonas aeruginosa.
Treating chronic infection is challenging because of increasing resistance of the bacteria to antibiotics and only a small number of antibiotics directly kill bacteria such as Pseudomonas aeruginosa. The macrolide antibiotics, which include erythromycin and azithromycin, have direct killing properties against some types of bacteria typically found in people with CF, in particular Staphylococcus aureus, but have no direct killing activity against others, such as Pseudomonas aeruginosa. There is, however, some laboratory evidence that macrolides may reduce the activity of Pseudomonas aeruginosa.
Therefore, our Cochrane Review aims to see whether macrolide antibiotics can improve the health of people with CF and whether there are any unwanted side effects. We're willing to include trials that compared macrolide antibiotics with either a placebo, a different macrolide antibiotic or the same macrolide antibiotic but at a different dose.
We found 14 eligible trials, which had a total of almost 1500 participants. Four of these trials were new for the 2024 update, adding just over 500 participants.
All 14 trials looked at the effects of azithromycin. Six enrolled only children, one enrolled only adults and seven enrolled both children and adults. The bulk of the evidence comes from the 11 trials that compared oral azithromycin with a matched placebo. There were also two trials that compared a high dose of azithromycin with a low dose, one that compared azithromycin inhaled as a mist with the drug taken orally and one that compared weekly versus daily doses.
Overall, we found that people taking azithromycin had a slight improvement in lung function after six months compared to those taking a placebo. They also had a lower risk of having a flare up of symptoms, known as a pulmonary exacerbation. Risks of side effects were similar in both groups. We have good certainty about these results because the trials were well conducted and included a large number of participants.
The trial of taking oral azithromycin once a week rather than every day showed that the weekly dose probably leads to less of an improvement in lung function but a longer time until a person has an exacerbation. We were moderately certain of this result, but it's based on only one trial and the dosing regimen used in the larger trials of azithromycin versus placebo was different: three times a week.
We're unsure about the evidence for the other comparisons, such as whether a higher dose of azithromycin was better than a lower dose or whether inhaled azithromycin was better than taking it orally. This is because the trials were smaller and there were risks of bias in how they were carried out.
In summary, we know that chronic infections are hard to treat and can reduce the quality and length of life of people with CF. However, we have enough evidence to say that six months of azithromycin can improve lung function and decrease exacerbations when compared to a placebo treatment; but there is no evidence to support a specific role in chronic Pseudomonas aeruginosa chest infection in people with CF. We also remain uncertain about the relative effects of different doses or ways of giving the antibiotics.
Finally, it's worth noting that azithromycin appears to have few side effects, is relatively inexpensive and doesn't significantly add to treatment burden for people with CF. On the other hand, though, there is a concern around the emergence of macrolide resistance and long-term data are needed to support the use of azithromycin therapy for everyone with CF.

Mike: If you'd like to find out more about the review and watch for future updates if that additional evidence becomes available, you can find it by going online to Cochrane Library dot com and searching with the words "macrolide and cystic fibrosis".