4- Week Vs 2 Weeks Course of Oral Amoxicillin - Clavulanate in Children with Suspected PBB

Introduction

Protracted bacterial bronchitis (PBB) is one of the leading causes of chronic wet cough in young children and is characterised by airway neutrophilia and chronic endobronchial infection. The current standard treatment in European and American guidelines is 2 weeks of antibiotics, but the optimal duration of therapy is unknown.

Aim

To test hypothesis that a 4-week course of oral amoxicillin–clavulanate is superior to a 2-week course in achieving clinical cure (cough resolution) in children with suspected PBB within 28 days

Patient Profile

Children aged 2 months to 19 years with chronic (>4 weeks duration) wet cough, and suspected PBB

Methods

• Parallel, double-blind, placebo-controlled, randomised controlled trial

 Study Outcome

• Primary outcome was clinical cure (cough resolution) by day 28
• Secondary outcomes were recurrence of PBB at 6 months, time to next exacerbation, change in Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) score from baseline to day 28 and from day 28 to 7 months, adverse events, nasal swab bacteriology, and antimicrobial resistance.

Results

• The primary endpoint of clinical cure in the 4-week group was not significantly different to the 2-week group (adjusted relative risk 0·87; p=0·49)

• Time to next wet cough exacerbation was significantly longer in the 4-week group than the 2-week group

Data are mean (SD), median (IQR), or n (%), unless otherwise stated. Participants assigned to the 2-week group were given 2 weeks of amoxicillin–clavulanate plus 2 weeks placebo. Those in the 4-week group were given 4 weeks of amoxicillin–clavulanate. HR=adjusted hazard ratio. All outcomes were adjusted for age, duration of cough at enrolment, and previous use of antibiotics for current cough. OR=adjusted odds ratio. PBB=protracted bacterial bronchitis. PC-QoL=Parent-proxy Cough-Specific Quality-of-Life. RR= adjusted relative risk. *Only those children with clinical cure by 28 days included (n=38 in the 2-week group and n=32 in the 4-week group).†Time to next exacerbation was calculated from the date of clinical cure with data censored at 180 days; children who did not have an exacerbation during follow-up were recorded as 181 days. ‡PC-QoL change was calculated for those children who had questionnaires completed at day 0 and day 28 and day 28 and 7 months, respectively.

• PC-QoL significantly improved from baseline to day 28 in both groups, but there was no significant difference between them (mean difference in change –0·2; p=0·64)
• From day 28 to 7 months, median PC-QoL remained stable in both groups with no difference in change between them
• Data on respiratory pathogens and antimicrobial resistance (paired swabs available for 48 children) were similar between groups

§Adverse event diaries were completed for 104 children with data missing for 2 children from the 2-week antibiotic group

Conclusion

• The study demonstrated that 4-week course of amoxicillin– clavulanate did not improve clinical cure by day 28 in children with PBB
• It was associated with improved symptom control during a 6-month follow-up with a significant 4-times increase in time to next wet cough exacerbation

Reference

Lancet Respir Med 2021; 9: 1121–29