The results of a small clinical trial in Australia indicate that a 4-week course of antibiotics for children with a chronic wet cough offers little advantage over 2 weeks, but some children may benefit from a longer course, Australian investigators reported yesterday in The Lancet Respiratory Medicine.
Patients had suspected protracted bacterial bronchitis
The double-blind, placebo-controlled trial was conducted at four Australian hospitals among children ages 2 months to 19 years of age who had a wet cough lasting more than 4 weeks and were suspected of having protracted bacterial bronchitis (PBB). Current US and European guidance for treatment of chronic wet cough with suspected PBB is 2 weeks of amoxicillin-clavulanate, extending to 4 weeks if the cough doesn't resolve, but there is some uncertainty about optimal treatment. The British Thoracic Society, for example, recommends 4 to 6 weeks.
To test whether a longer course of antibiotic therapy may be preferable for the condition, investigators at the four hospitals randomly assigned 106 children from March 2017 through September 2019 to receive either 2 weeks of amoxicillin-clavulanate or 4 weeks, with all children, caregivers, investigators, and study coordinators masked to treatment assignment. The primary outcome was clinical cure (cough resolution) by day 28.
Secondary outcomes include the time to next cough exacerbation, recurrence of PBB at 6 months, the Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) score from baseline to day 28 and from day 28 to 7 months, adverse events, and prevalence of antimicrobial resistance.
A total of 106 children were included in the trial, with 52 in the 4-week group and 54 in the 2-week group. Most baseline demographics and clinical characteristics were similar between the two groups, but the children in the 4-week group were slightly older (median 2.2 vs 1.7 years).
By day 28, the proportion of children in each group who achieved clinical cure was similar—32 of 52 children (62%) in the 4-week group and 38 of 54 (70%) in the 2-week group (adjusted relative risk, 0.87; 95% confidence interval [CI], 0.60 to 1.28). In the 4-week group, however, the time to next cough exacerbation was four times longer than in the 2-week group (median 150 days vs 36 days; adjusted hazard ratio, 0.47; 95% CI, 0.25 to 0.90.).
The investigators also found that the rate of recurrence of PBB within the 6-month follow-up was reduced in the 4-week group compared with the 2-week group (53% vs 74%). But the difference was not considered significant (adjusted odds ratio, 0.39; 95% CI, 0.14 to 1.04).
"These results suggest the use of 4 weeks of antibiotics might provide greater wet cough symptom control across 6 months follow-up than 2 weeks of treatment," the study authors wrote.
The PC-QoL score improved significantly in both groups from baseline to day 28, with no significant difference between the two groups, and remained stable in both groups, with no significant difference, from day 28 to 7 months.
No differences were found between the two groups in the prevalence of pathogens or antimicrobial resistance identified. Adverse events occurred in 10 of 52 children (19%) in the 4-week group and 13 of 54 (25%) in the 2-week group.
Identifying who may benefit from longer therapy
The authors say that although the findings do not support altering current guidance on antibiotic treatment, they do indicate a need to identify which children with PBB may benefit from an additional 2 weeks of antibiotics, as there increasing evidence to suggest that if left untreated, chronic wet cough can progress to chronic suppurative lung disease, and then bronchiectasis—a condition in which the bronchial tubes are permanently damaged. But they note that antimicrobial stewardship is an important consideration.
"Unnecessary use of antibiotics promotes increased antimicrobial resistance, while inadequate treatment might be associated with poorer clearance of airway pathogens with ongoing airway inflammation and recurrent PBB," they wrote. "Larger, placebo-controlled, randomized controlled trials that incorporate different populations and have longer duration of follow-up are required."
