Introduction

Amoxycillin is used in patients with recurrent otitis media or therapeutic failure after treatment with penicillin although it is susceptible to degradation by beta-lactamases. In amoxycillin/clavulanate combination therapy, clavulanic acid is a potent inhibitor of beta-lactamase and protects amoxycillin from breakdown.

Aim

To compare clinical efficacy of amoxycillin/clavulanate with that of amoxycillin in children with recurrent otitis media and therapeutic failure, and investigate the bacterial aetiology in this patient population.

Patient Profile

91 children (aged 6 months to 10 years) with recurrent otitis media or therapeutic failure after treatment with phenoxymethyl penicillin of at least 3 days duration or had a relapse within 30 days after the initial episode

Method

Study Design

• Comparative, randomized and double-blind study with two parallel groups
• One group was given amoxycillin 25 mg/ml and clavulanate 6.25 mg/ml suspension for 7 days and the other group was given amoxycillin 25 mg/ml suspension for 10 days

Endpoints

• Clinical result was rated as ‘cured’ (normal appearance and mobility of the eardrum and a normal tympanogram, type A or C), ‘improved’ (no signs of acute otitis media but with serous or mucous middle ear fluid and an abnormal tympanogram, type B) or ‘failure’ (persisting or new signs and symptoms of acute otitis media)
• Bacteriological outcome was rated as ‘elimination’ (initial pathogens) eradicated and no new pathogens present), ‘recolonization’ (initial pathogen(s) eradicated but new pathogens present), ‘persistence’ (one or more of the initial pathogens still present) or ‘unassessable’ (impossible to evaluate due to no pathogen initially or no sample at the follow-up visit)

Results

Efficacy

• Amoxycillin/clavulanate and amoxycillin showed equally high, satisfactory treatment results with >90% response: over 90% were cured or improved at first follow-up and at the second follow-up, 88% in the amoxycillin/clavulanate group and 77% in the amoxycillin group were cured or improved
• No significant difference was seen between the treatment groups at the second follow-up visit (about 30 days after start of treatment)
• Bacteriological cultures from the nasopharynx showed equal distribution of Haemophilus influenzae, Branhamellla catarrhalis and Streptococcus pneumoniae between the study groups
• The bacteriological outcome at the first follow-up visit showed better elimination (36% vs. 26%) and less recolonization (10% vs. 21%) for patients on amoxycillin compared with those on amoxycillin/clavulanate
• Elimination of the initially occurring pathogens was equal in the two study groups with the exception of B. catarrhalis which was eliminated to a significantly higher extent with amoxycillin/clavulanate (p=0.022)
• In children with beta-lactamase producing strains, amoxycillin/clavulanate was significantly superior to amoxycillin in elimination of beta-lactamase producing B. catarrhalis; this difference remained even when the non-beta-lactamase producing B. catarrhalis strains were added

Safety 

• Both antibiotics were well tolerated with few side effects
• Three patients discontinued treatment in the amoxycillin group (skin rash and vomiting), and one in the amoxycillin/clavulanate group (diarrhoea)
• Compliance measurements showed that the antibiotic dosages had been well followed and that the average patient had received about 10% over the expected amount for 10 days (30 doses)

Conclusion

• In children with recurrent otitis media or therapeutic failure, treatment with amoxycillin/clavulanate for 7 days resulted in high, satisfactory clinical efficacy and was comparable to treatment with amoxycillin for 10 days
• When beta-lactamase producing B. catarrhalis was present, amoxycillin/clavulanate showed statistically better elimination than amoxycillin

Acta Oto-Laryngologica 2009; 111: 120-129