Introduction 

Azithromycin exhibited high pharmacokinetic distribution into target tissues, and displayed a broad antimicrobial spectrum. Significant clinical improvement has been achieved in pediatric bacterial pharyngitis and/or tonsillitis treated with 10 mg of azithromycin/kg of body weight for 3 days, however, lower success rates have also been reported. Azithromycin administration at doses higher than standard regimens may improve eradication rates in pharyngitis and tonsillitis.

Aim

To compare azithromycin concentrations in tonsils and plasma collected from pediatric patients with tonsillitis treated with 10 or 20 mg/kg daily for 3 days

Patient Profile 

Method

Study Design

• Patients were treated with oral suspension of 10 or 20 mg of azithromycin per kg of body weight for 3 days
• Azithromycin levels in plasma and tonsil samples were determined up to 8.5 days after the last dose.

Endpoints

Results 

Efficacy 

• Azithromycin concentrations in tonsils were significantly higher after administration of 20 mg/kg versus 10 mg/kg up to day 6.5 (from +48.2 to +56.4%)
• The ratio of tissue AUC at 20 mg/kg dose (105.9 mg/kg.day) over AUC at 10 mg/kg (69.19 mg/kg.day) was 1.53
• Consistent azithromycin levels in tonsils were detected up to 8.5 days (4.6 mg/kg)
• The plasma levels of azithromycin 10 mg/kg were similar to that of 20 mg/kg regimen (0.13 mg/liter and 12.1 mg/kg in samples collected 0.5 and 2.5 days after the last dose, respectively)
• The ratio of plasma AUC value at 20 mg/kg (0.72 mg/liter.day) over AUC value at 10 mg/kg (0.62 mg/liter.day) was 1.16
• The time courses of azithromycin disposition in plasma and tonsils were similar to those obtained with 20 mg/kg or 10 mg/kg dose

Safety   

• Two patients experienced mild nausea and abdominal pain that occurred at the third day of therapy and were likely to be induced by azithromycin
• No abnormalities of electrocardiogram, blood chemistry, hematology, or urine analysis were observed

Conclusion 

• The 20-mg/kg regimen of azithromycin achieved higher tonsillar distribution and was well tolerated by pediatric patients as compared to 10 mg/kg daily for 3 days
• These results suggested achievement of enhanced and sustained therapeutic azithromycin concentrations at infective sites of the upper respiratory tract

Antimicrobial Agents Chemotherapy 2002; 1594-1596