The first randomised controlled trial to investigate the optimal duration of antibiotic treatment for wet cough and protracted bacterial bronchitis in children has produced mixed results for extending treatment beyond two weeks.

While a four week course of amoxicillin-clavulanate was no different to a two week course in terms of cough resolution, it did result in better symptom control over six months, Australian researchers found.

In a study led by Dr Tom Ruffles of the Queensland Children’s Hospital, 106 children with protracted bacterial bronchitis (median age two year) were randomly assigned  to  receive two or four weeks   of amoxicillin–clavulanate as a twice-daily oral suspension.

For the primary outcome of cough resolution by day 28, there was no difference between the two and four week treatment groups (70% vs 62%).

However the time until next exacerbation was four times longer in the four-week group than the two-week group (median 150 vs 36 days; adjusted hazard ratio 0·47, p=0·02).

The rate of recurrence at six months was lower in four week group compared with the two week group (53% vs 74%) but the difference was no significant.

There were no differences in quality of life or in microbial resistance between the two groups.

Writing in Lancet Respiratory Medicine, Dr Ruffles and colleagues said that until now there had been a paucity of evidence to guide treatment decisions for children with wet cough and likely PBB.

They noted that currently some guidelines such as those from the British Thoracic Society recommend an initial course of four to six weeks duration, while most recommend two weeks.

And although four weeks of antibiotics did not improve clinical cure  at 28 days compared with a two-week course, there was still a case for prescribing longer courses, they suggested.

“There is insufficient evidence to support an alteration from current guidance of an initial 2-week course of antibiotics for PBB that can be extended up to a total of 4 weeks if cough resolution has not occurred. However, some children could benefit from a 4-week course, as this longer duration of antibiotics led to a longer cough-free period,” they wrote.

They also noted that the improved wet cough symptom control provided by an initial four-week course of antibiotics resulted in a similar mean total antibiotic duration between the groups during the trial and at 6-months follow-up.

“Taken in context with the finding of no difference between the groups for antimicrobial resistance of nasal respiratory pathogens, these results provide reassurance of responsible prescribing when a four-week course of antibiotics is being considered for treatment of suspected PBB.”

An accompanying commentary article highlighted the finding that one third of children with a clinical suspicion of PBB did not subsequently meet the diagnostic criteria due to a failure to achieve cough resolution.

“The lack of difference in cough resolution between groups suggests for non-responders there is little apparent benefit in extending the antibiotic course beyond two weeks as currently recommended. These children should instead be investigated for a cause other than PBB,” the authors said.

For children who did improve following initial treatment, the differences in cough exacerbation and possibly relapse “might be important enough to warrant a longer initial course in responders,” they added.

They proposed a further RCT of two week versus six week courses of antibiotics for wet cough, to address the hypothesis that extending the initial treatment beyond that required for symptom resolution would enable damaged epithelium to repair and mucociliary clearance to improve, thereby reducing relapses.