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 influenzae including ampicillin-resistant strains. We evaluated the efficacy of azithromycin, clarithromycin and three beta -lactams when used for 1 day only and for 3 days for the treatment of a murine model of bronchopneumonia, using 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-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae were 32 times higher than those for beta-lactamase-positive ampicillin-resistant and ampicillin-susceptible strains. The viable counts in the infected tissues of azithromycin-treated mice with bronchopneumonia caused by the susceptible strain TUM8, beta-lactamase-positive strain TUH36 and BLNAR strain TUH267 were less than the counts obtained with the other antibiotics used, irrespective of MIC. At a dose of 50 mg/kg, the area under the concentration curve and the half-life of azithromycin in the lungs were respectively three times higher and six times longer than those of clarithromycin. Our results indicate that azithromycin may be useful for both ampicillin-susceptible and ampicillin-resistant bronchopneumonial infections caused by H. influenzae.
Miyazaki
S
S
Department of Microbiology, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan. shuichi@med.toho-u.ac.jp
Fujikawa
T
T
Matsumoto
T
T
Tateda
K
K
Yamaguchi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D001996:Bronchopneumonia / Q000188:drug therapy* / Q000382:microbiology; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000188:drug therapy*; D006193:Haemophilus influenzae / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D016896:Treatment Outcome; D047090:beta-Lactams / Q000008:administration & dosage / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D017963:Azithromycin; D017291:Clarithromycin