Antibiotic treatment is recommended for group A b-haemolytic
streptococcal pharyngitis to prevent rheumatic fever,
hasten symptom resolution, limit transmission, and prevent
suppurative complications [1].
Several studies have documented the efficacy of the azithromycin
immediate-release formulation (AZ-IR) when given
for 3 days (500 mg once daily) to adults with streptococcal
pharyngitis/tonsillitis [2–4], and this 3-day treatment has been
approved in many countries. In children, a 3-day course of
azithromycin totalling 60 mg/kg has proved more effective
than 30 mg/kg, and bacteriological failure was five-fold lower
in patients receiving 60 mg/kg over 3 days than in those treated
with 10-day courses of comparators [5].
A novel microsphere-based azithromycin extended-release
formulation (AZ-ER) allows administration of a higher oral
dose of azithromycin as a single-dose regimen, while maintaining
tolerability [6]. Drug exposure after a single 2-g oral
dose of AZ-ER is considerably higher than that achieved with
a 1.5-g total dose of AZ-IR administered over 3 or 5 days.
This so-called ‘front-loading’ of the dose early during the
course of infection maximizes drug exposure when the bacterial
burden is highest. Front-loading increases the AUC0–24/
MIC ratio, the parameter that best predicts azithromycin
efficacy [7]. Data from animal infection models suggest that
this approach is effective in a variety of infections [8] (Kamicker
et al., 44th ICACC, 2004, Abstract 1181B). In addition,
clinical trials have demonstrated that AZ-ER is as effective
and well tolerated as comparator antibiotics in the treatment
of community-acquired pneumonia, acute exacerbations of
chronic bronchitis, and acute bacterial rhinosinusitis [9–12].Therefore, this study was performed to confirm whether a
single 2-g oral dose of AZ-ER is bacteriologically non-inferior
to a 500-mg once-daily dose for 3 days of AZ-IR when used
to treat adults and adolescents with group A b-haemolytic
streptococcal pharyngitis/tonsillitis.