In vitro and in vivo evaluation of the antimicrobial activity of azithromycin againstLegionella species

The antimicrobial activity of azithromycin (AZM) was evaluated againstLegionella species using an experimental model of legionellosis. The minimum inhibitory concentration₉₀s (MIC₉₀s) of AZM against 35 standard strains (0.25 mg/L) and 22 Japanese clinical isolates ofLegionella pneumophila (0.063 mg/L) were lower than those of erythromycin (EM) and almost equal to those of clarithromycin and roxythromycin. Using¹⁴C-labeled antibiotic, AZM and EM were observed concentrated inside human polymorphonuclear leukocytes (PMN) with intracellular/extracellular concentration ratios of AZM and EM at 120 minutes after dosing of 27.3 and 22.2, respectively. AZM inhibited the growth ofL. pneumophila (80-045 strain) from cultured guinea pig alveolar macrophages, even when the extracellular AZM was washed out on day 2 of culture. However, the addition of identical concentrations of EM failed to produce a similar inhibition. Pharmacokinetic studies of AZM tissue distribution in guinea pigs infected withL. pneumophila 80-045 revealed high drug concentrations in the lung and liver and a longer half-life in these organs compared with those in plasma. Treatment of guinea pigs with experimentally-induced legionellosis with oral AZM (10 mg/kg/day for 2 days) was more effective than EM treatment (10 mg/kg/day for 4 days) or a placebo, and resulted in a significant improvement in the survival rate. Our results suggest that AZM is a promising new drug for the treatment of legionellosis using a short-term dosing regimen.