Amoxycillin Clavulanate Effective in Children with Chronic Wet Cough

Introduction

Protracted bacterial bronchitis (PBB) is common in children with chronic wet cough. Clinical guidelines recommend antibiotic therapy for children with PBB.

Aim

To assess the efficacy of oral amoxycillin clavulanate compared with placebo in achieving cough resolution in children with chronic wet cough

Patient Profile

50 children (aged 6 months to <18 years) with chronic (>3 weeks) wet cough

Method

Study Design

• Parallel double-blind randomised controlled trial
• Children were randomised to either oral amoxycillin clavulanate twice daily for 2 weeks or placebo
• In selected children, bronchoalveolar lavage (BAL) was undertaken at baseline.

Endpoints

• Primary outcome: ‘cough resolution’, defined as an improvement in baseline cough score (>75% reduction in cough score) at ‘end of trial’ or cessation of coughing for a minimum period of 3 days within the trial period
• Baseline cough score: average score in the 2 days immediately before trial medication commencement
• ‘End of trial’ score: average score of the 2 days immediately following completion of 14 days of medication
• Secondary outcomes: absolute change in cough score and change in verbal category descriptive (VCD) score

Results

Efficacy

• Amoxycillin clavulanate achieved significantly higher cough resolution rates as compared to placebo (48% versus 16%, p=0.016); these children continued to remain cough-free at 4 weeks and a further two children in the treatment group had ceased coughing
• The observed difference between proportions was 0.32, odds ratio was 4.85 and number needed to treat was 4 at 2 weeks
• On day 28, coughing ceased in 77% children in the treatment group who had significant bacteria growth on pre-treatment BAL
• Amoxycillin clavulanate group achieved a significantly lower and better VCD scores as compared to the placebo group post treatment (0.5 versus 2.25, p=0.02)
• Pre-treatment BAL data were consistent with protracted bacterial bronchitis (PBB) in the majority of children

Figure 1: Cough resolution rate with amoxycillin clavulanate and placebo

Safety 

• No significant difference seen in the side effects in both the groups
• Two patients in the placebo group and five in the amoxycillin clavulanate group had mild diarrhoea (difference in proportions of -0.12)
• One child in the amoxycillin clavulanate group had vomiting and stopped the trial drug on day 3

Conclusion

• Amoxycillin clavulanate was effective in cough resolution in a significant number of children with isolated chronic wet cough in 2 weeks
• This study has provided the first high-level evidence for the inclusion of antibiotics in paediatric cough-specific guidelines as treatment for PBB and chronic moist cough

Thorax 2012; 67: 689-693