According to an editorial, though these data are encouraging, there are important caveats to consider: first, inclusion criteria were relatively narrow limiting the generalisability. Second, azithromycin treatment was not linked to reductions in urgent care, emergency department visits, or hospitalisations, nor did it prevent subsequent episodes with symptoms significant enough to qualify for initiation of azithromycin. Third, specific subgroup characteristics in which the risk of progression was greater, and the benefit more profound, could not be identified. It adds that the implications of the study must also be interpreted in light of the reality that more widespread azithromycin use for a condition as common as early, intermittent childhood wheezing would increase the prevalence of macrolide resistance.
The commentators note the suggestion made by the researchers that clinicians may consider a therapeutic trial of azithromycin in children with recurrent intermittent wheezing early in the course of acute episodes, and if effective, to consider repeating such therapy with subsequent illnesses, may make the most sense for children with multiple frequent episodes, as NNT to prevent a severe episode decreased from 33 among children with 1 qualifying respiratory tract infection (RTI) to 7 among those with 4 qualifying RTIs. However, they caution that without an objective measure of whether or not a specific child’s episodes are modified by this approach, it is likely to promote widespread use despite the benefit being limited to a few. They acknowledge that limiting children’s loss of days from school (or parents’ days from work) and relieving the anxiety that an RTI that may progress to a hospitalisation is likely to be of benefit to children and families, but the question remains of how to determine which children are most likely to obtain the largest benefit from early initiation of azithromycin. They advise that until a higher-risk population can be prospectively identified for progression to severe LRTI, the consequences of widespread use of azithromycin, both known and hypothesised, outweigh the benefit for most children.