Efficacy of azithromycin, clarithromycin and beta-lactam agents against experimentally induced bronchopneumonia caused by Haemophilus influenzae in mice

Azithromycin is an azalide with potent activity against Haemophilus influen zae including ampicillin-resistant strains. We evaluated the efficacy of az ithromycin, clarithromycin and three beta -lactams when used for 1 day only and for 3 days for the treatment of a murine model of bronchopneumonia, us ing three strains of H. influenzae, two of which were ampicillin resistant. MICs of azithromycin (1-2 mg/L) and clarithromycin (4-8 mg/L) were similar for the three strains. The MICs of cefdinir and cefcapene for beta -lactam ase-negative ampicillin-resistant (BLNAR) H. influenzae were 32 times highe r than those for beta -lactamase-positive ampicillin-resistant and ampicill in-susceptible strains. The viable counts in the infected tissues of azithr omycin-treated mice with bronchopneumonia caused by the susceptible strain TUM8, beta -lactamase-positive strain TUH36 and BLNAR strain TUH267 were le ss than the counts obtained with the other antibiotics used, irrespective o f MIC. At a dose of 50 mg/kg, the area under the concentration curve and th e half-life of azithromycin in the lungs were respectively three times high er and six times longer than those of clarithromycin. Our results indicate that azithromycin may be useful for both ampicillin-susceptible and ampicil lin-resistant bronchopneumonial infections caused by H. influenzae.