Edelstein P H, Shinzato T, Doyle E, Edelstein M A
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
Antimicrob Agents Chemother. 2001 Aug;45(8):2204-9. doi: 10.1128/AAC.45.8.2204-2209.2001.
The activity of gemifloxacin against intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia was studied. Gemifloxacin, azithromycin, and levofloxacin (1 microg/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 2 to 3 log(10) units. Gemifloxacin and levofloxacin had roughly equivalent intracellular activities. In contrast, erythromycin had static activity only. Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with L. pneumophila pneumonia. When gemifloxacin (10 mg/kg) was given by the intraperitoneal (i.p.) route to infected guinea pigs, mean peak levels in plasma were 1.3 microg/ml at 0.5 h and 1.2 microg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.3 h, and the area under the concentration-time curve from 0 to 24 h (AUC(0--24)) was 2.1 microg. h/ml. For the same drug dose, mean levels in lungs were 3.4 microg/g at both 0.5 and 1 h, with a half-life of 1.5 h and an AUC(0--24) of 6.0 microg. h/ml. All 15 L. pneumophila-infected guinea pigs treated with gemifloxacin (10 mg/kg/dose given i.p. once daily) for 2 days survived for 9 days after antimicrobial therapy, as did 13 of 14 guinea pigs treated with the same dose of gemifloxacin given for 5 days. All 12 azithromycin-treated animals (15 mg/kg/dose given i.p. once daily for 2 days) survived, as did 11 of 12 animals treated with levofloxacin (10 mg/kg/dose given i.p. once daily for 5 days). None of 12 animals treated with saline survived. Gemifloxacin is effective against L. pneumophila in infected macrophages and in a guinea pig model of Legionnaires' disease, even with an abbreviated course of therapy. These data support studies of the clinical effectiveness of gemifloxacin for the treatment of Legionnaires' disease.
研究了吉米沙星对细胞内嗜肺军团菌的活性以及对嗜肺军团菌肺炎豚鼠的治疗效果。吉米沙星、阿奇霉素和左氧氟沙星（1微克/毫升）可使在豚鼠肺泡巨噬细胞中生长的两株嗜肺军团菌的细菌计数减少2至3个对数（10）单位。吉米沙星和左氧氟沙星具有大致相当的细胞内活性。相比之下，红霉素仅具有抑菌活性。对吉米沙星、阿奇霉素和左氧氟沙星进行了针对嗜肺军团菌肺炎豚鼠的治疗研究。当对感染的豚鼠腹腔注射（i.p.）吉米沙星（10毫克/千克）时，血浆中的平均峰值水平在注射后0.5小时为1.3微克/毫升，1小时为1.2微克/毫升。从血浆中消除的终末半衰期为1.3小时，0至24小时的浓度-时间曲线下面积（AUC(0--24)）为2.1微克·小时/毫升。对于相同的药物剂量，肺中的平均水平在0.5小时和1小时均为3.4微克/克，半衰期为1.5小时，AUC(0--24)为6.0微克·小时/毫升。所有15只接受吉米沙星（10毫克/千克/剂量，每天腹腔注射一次）治疗2天的嗜肺军团菌感染豚鼠在抗菌治疗后存活9天，14只接受相同剂量吉米沙星治疗5天的豚鼠中有13只存活。所有12只接受阿奇霉素治疗的动物（15毫克/千克/剂量，每天腹腔注射一次，共2天）存活，12只接受左氧氟沙星治疗的动物（10毫克/千克/剂量，每天腹腔注射一次，共5天）中有11只存活。12只接受生理盐水治疗的动物均未存活。即使疗程缩短，吉米沙星在感染的巨噬细胞和豚鼠军团病模型中对嗜肺军团菌也有效。这些数据支持对吉米沙星治疗军团病临床有效性的研究。
