Therapeutic activity and local delivery of azithromycin in animal models of local infection

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  • 動物局所感染モデルにおけるAzithromycinの治療効果および組織移行性

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We compared the therapeutic efficacy of azithromycin (AZM), in several localized infection models, with those of clarithromycin (CAM), tosufloxacin (TFLX) and cefaclor (CCL). Local delivery of AZM and CAM to infection sites was also studied.<BR>In a rat pouch infection with Staphylococcus aureus, 30mg/kg doses of AZM at 0, 6 and 24h postchallenge reduced the CFU by approximately 99% from the initial inoculum. Although the MIC of AZM was 4 and 16 fold higher than that of CAM and TFLX, respectively, AZM demonstrated greater therapeutic efficacy than CAM and TFLX.<BR>In a murine model of subcutaneous infection with Streptococcus pyogenes, 25mg/kg (twice a day) doses of AZM at 1 and 2 days post-challenge produced a 99% reduction of CFU as compared to an untreated control. These effects of AZM were much greater than those of CAM, even though CAM exhibited greater in vitro potency.<BR>In a murine respiratory infection model with Haemophilus influenzae, a single dose of AZM (50 mg/kg) at 4h post-challenge significantly (p<0.01) reduced the CFU as compared with CAM and the untreated control. AZM produced more than 40 times higher concentrations in lungs than in serum, and the lung concentrations exceeded the MIC for the pathogen until at least 48 h post-dosing. Lung concentrations of AZM in infected mice were significantly (p<0.01) higher than in non-infected mice.<BR>These results suggest that AZM may have good clinical efficacy in localized human infections because of its high, and prolonged, levels in tissues.

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