Introduction

Studies in children with acute otitis media, have shown that azithromycin has been clinically effective when administered as a 5-day dosing regimen. However, a 3-day azithromycin dosing regimen (with same total dose as 5-day regimen) may improve compliance, simplify therapy and be more effective when the bacterial burden is highest.

Aim

To compare a 3 day regimen of azithromycin with 10 day regimen of co-amoxiclav in children with acute otitis media (AOM) 

Patient Profile

• 373 children (6 months - 12 years of age) with symptoms (ear pain or fullness, discharge from the external auditory canal, decreased hearing or fever) and signs of AOM (bulging or marked erythema of the tympanic membrane, loss of the normal light reflex or tympanic membrane landmarks, or impaired tympanic mobility) for <4 weeks and tympanic membrane effusion

Method

Study Design

• Randomized, double-blind study
• Children were randomized to azithromycin 10 mg/kg/day once daily and a matching placebo for 3 days or co-amoxiclav 45 mg/kg/day in divided doses twice daily and a matching placebo for 10 days

Endpoints

• Primary endpoint: clinical response at day 28
• Patient compliance

Results

Efficacy

• Azithromycin treatment achieved an equivalent clinical success rate at day 10 (83% vs. 88%, p=186) and cure rate at day 28 (74% vs. 69%, p=0.353) as compared to co-amoxiclav treatment in children with AOM (Figure 1)
• Azithromycin was associated with low frequency of signs of AOM, such as abnormal acoustic reflectometry (45% vs. 59%; P = 0.017) indicating a persistent middle ear effusion versus co-amoxiclav at days 24–28
• Co-amoxiclav was more frequently associated with abnormalities of the tympanic membrane: bulging of the eardrum (16% vs.10%; P = 0.059) and loss of landmarks (22% vs. 11%; P = 0.010) as compared to azithromycin at days 24–28; however, these signs were observed more frequently in the azithromycin group at day 10 vs. co-amoxiclav (bulging 22% vs. 13%, loss of landmarks 31% vs 20% & impaired TM mobility 39% vs. 28%)
• During the first 10 days of the study, the proportion of children administered an additional antibiotic was similar regardless of study drug (azithromycin group 5.9%; co-amoxiclav group 3.9%)

Figure 1: Clinical cure rate at day 28 with azithromycin in comparison with co-amoxiclav

Safety 

• Azithromycin treatment was associated with lower adverse events related to therapy as compared to co-amoxiclav treatment (11% versus 20%, respectively; P = 0.014)
• The commonly observed events were diarrhoea (14.6% for co-amoxiclav and 5.9% for azithromycin; P = 0.006), rash (4.3% and 0%, respectively; P = 0.003) and vomiting (1.1% and 2.1%, respectively; P = 0.685)
• Azithromycin treatment achieved higher compliance versus co-amoxiclav treatment (99% vs. 89%)

Conclusion

• Azithromycin treatment given over 3 days was as effective by clinical criteria as co-amoxiclav for treatment of AOM and was better tolerated
• An improvement was achieved in the tympanic membrane disease with azithromycin, unlike with co-amoxiclav between day 10 and days 24–28

J Antimicrobial Chemother 2003; 52: 469-472