Introduction

Azithromycin, a macrolide antibiotic, has demonstrated improved activity against Gram-negative pathogens (Haemophilus influenzae and Moraxella catarrhalis) and other pathogens (Streptococcus pyogenes and Streptococcus pneumoniae). Azithromycin administration in adults has been shown to achieve high tissue concentrations (>100 times; 4.5 mg/kg in tonsillar tissue, with a half-life of 76 h after two 250-mg doses at a 12-h interval) versus those in serum. This data confirmed that azithromycin 500 mg given once daily for 3 days would maintain tonsillar levels at >2 mg/L for over 10 days. This was above the minimum inhibitory concentration of azithromycin against common upper respiratory tract pathogens.

Aim

To assess azithromycin concentrations in the tonsils and/or adenoids of children scheduled for surgical removal of these tissues

Patient Profile

• 23 children (1.6-7.5 years old) undergoing surgical removal of their tonsils and/or adenoids

Method

Study Design

• Open-label non-randomized study
• Children were allocated to one of four groups (groups I-IV) depending upon whether surgery was scheduled for 1, 2, 4 or 8 days after the final dose of azithromycin
• They received azithromycin oral suspension 10 mg/kg once daily for 3 consecutive days, 90 min before the evening meal.

Endpoints

• Azithromycin levels were determined from tonsillar and/or adenoid tissue samples and serum samples obtained at the time of surgery

Results

Efficacy

• The mean tissue concentrations of azithromycin were similar in those tissues obtained at 4 days versus those obtained at 1- or 2-days post-treatment (Figure 1)
• Azithromycin levels obtained 8 days after treatment were significantly lower (P < 005) versus those obtained 1-day post-treatment (Figure 1)
• At the earlier assessments, tissue azithromycin concentrations were >2 mg/kg, whereas for the 8-day assessment tissue concentrations were between 1 and 2 mg/kg in all except one patient
• In contrast to tissue levels, serum azithromycin concentrations were highest for 1-day after the end of treatment (47.25 µg/L) and progressively decreased (14.00 µg/L at 2 -day, 8.00 µg/L at 4-day) until after 8 days they were below the limits of detection (<4 µg/L)
• The mean tissue: serum concentration ratio was highest in the group assayed 4 days after treatment and was significantly higher (P < 005) than at day 1 after treatment (956 at 4-day vs. 227 at day 1) 

Figure 1: Mean tissue concentrations of azithromycin

Safety 

• No adverse events were attributed to azithromycin, even in those given a single dose

Conclusion

• The levels of azithromycin in tonsillar and adenoid tissue were consistently higher than in serum and were maintained for 8 days after the end of dosing and that the values were consistent with those predicted in adults
• The study supported the use of a short-course (3-day), once-daily regimen of azithromycin in children for the treatment of upper respiratory tract infections 

J Antimicrob Chemother 1996; 37(Suppl. C): 45-51