Introduction

Long term treatment with penicillin for 10 days in Group A Streptococcus infection, is associated with risks. A basic rule of antimicrobial drug treatment is short-term treatment at sufficiently high dose levels.

Aim

To compare the efficacy of 3-day treatment with a combined clavulanate/amoxicillin preparation and 10-day treatment with amoxicillin in pediatric pharyngolaryngitis and tonsillitis caused by Group A β-hemolytic Streptococcus

Patient Profile

97 children (<15 years) with pharyngolaryngitis or tonsillitis caused by Group A β-hemolytic Streptococcus infection

Method

Study Design

• An active drug-controlled, open-label, multicentre study
• Clavulanate/amoxicillin preparation (CVA/AMPC) group: 3-day treatment with a combined CVA/AMPC preparation 96.4 mg/kg/day (CVA 6.4 mg/kg/day, AMPC 90 mg/kg/day) in two divided doses
• Amoxicillin (AMPC) group: 10-day treatment with AMPC 30 mg/kg/day in three divided doses
• Each patient was followed for approximately 1–2 weeks after completion or discontinuation of treatment

  Endpoints

• Primary endpoint: clinical efficacy

Results

Efficacy

• CVA/AMPC group showed equivalent clinical efficacy rate and clinical response rate as that of AMPC group upon completion of treatment (92.6% and 98.1% vs. 88.1% and 92.9%)
• In both groups, body temperature in most patients had decreased to <37.5°C by the time of treatment completion/discontinuation
• The Group A β-hemolytic Streptococcus eradication rate at approximately 1–2 weeks after completion/discontinuation of treatment was significantly higher in the AMPC group versus the CVA/AMPC group (85.4 % vs. 65.4 %, p<0.05)
• The eradication rate for Streptococcus pneumoniae and for Neisseria tended to be higher in the CVA/AMPC group than in the AMPC group; no difference observed for Haemophilus influenzae, Moraxella catarrhalis, or α-hemolytic Streptococcus
• Relapse/recurrence of clinical symptoms was not seen even in cases from which the pathogen continued to be isolated
• The minimum inhibitory concentration (MIC) of both CVA/AMPC and AMPC against each strain of the bacterium (<0.06 µg/ml) indicated that all strains were susceptible to both drugs

Figure 1: Comparison of the clinical effects of CVA/AMPC and AMPC on efficacy and response rates

Safety 

• The incidence of diarrhea was significantly higher in the CVA/AMPC group (46.8 %) than in the AMPC group (12.8 %, p<0.01); diarrhea resolved during continued treatment or after the completion of treatment
• Urticaria and eruption were noted in the CVA/AMPC group, and upper airway inflammation was seen in the AMPC group, but none of them were severe
• Discontinuation of test drug treatment because of an adverse reaction occurred in one patient (urticaria) from the CVA/AMPC group and one patient (diarrhea) from the AMPC group

Conclusion

Clavulanate/amoxicillin 3-day treatment was clinically effective alternative in treating pediatric pharyngolaryngitis and tonsillitis caused by Group A β-hemolytic Streptococcus.

J Infect Chemother 2013; 19: 12–19