Truccolo Johann, Charavay Françoise, Merien Fabrice, Perolat Philippe
Leptospira Laboratory, Institut Pasteur de Nouvelle-Calédonie, 98845 Nouméa Cedex, New Caledonia.
Antimicrob Agents Chemother. 2002 Mar;46(3):848-53. doi: 10.1128/AAC.46.3.848-853.2002.
The susceptibility of Leptospira interrogans serovar icterohaemorrhagiae strain Verdun to selected antibiotics used in medical practice (ampicillin, doxycycline, and ofloxacin) was evaluated in a Syrian hamster model, to determine the efficacy of these antibiotics during the course of the disease. A quantitative PCR assay was used to monitor the density of leptospires in blood and in target organs (liver, kidney, lung, heart, and spleen). Our results demonstrated the ability of ampicillin at a high dose (100 mg/kg of body weight) to clear leptospires from the host, except from kidneys and heart, where 10(2) leptospires/g remained at day 6. Ofloxacin (30 mg/kg) was unable to clear bacteria from blood or kidneys. With doxycycline (10 mg/kg), the clearance of leptospires occurred in 2 days in all the target organs studied, with the exception of liver, which required 3 days. Our data demonstrate the value of monitoring the kinetics of experimental leptospiral infection in order to accurately evaluate the efficacy of antibiotics. We have demonstrated the potential value of doxycycline for the treatment of leptospirosis cases, except in circumstances where it is contraindicated. This experimental model could be used to define better therapeutic strategies for human leptospirosis, by testing associations or new formulations of antibiotics.
在叙利亚仓鼠模型中评估了问号钩端螺旋体黄疸出血型菌株凡尔登对医学实践中使用的选定抗生素(氨苄西林、多西环素和氧氟沙星)的敏感性,以确定这些抗生素在疾病过程中的疗效。使用定量PCR测定法监测血液和靶器官(肝脏、肾脏、肺、心脏和脾脏)中钩端螺旋体的密度。我们的结果表明,高剂量(100mg/kg体重)的氨苄西林能够从宿主体内清除钩端螺旋体,但肾脏和心脏除外,在第6天时肾脏和心脏中仍有10²个钩端螺旋体/g。氧氟沙星(30mg/kg)无法从血液或肾脏中清除细菌。使用多西环素(10mg/kg)时,除肝脏需要3天外,在所研究的所有靶器官中,钩端螺旋体在2天内被清除。我们的数据表明监测实验性钩端螺旋体感染动力学对于准确评估抗生素疗效的价值。我们已经证明了多西环素在治疗钩端螺旋体病病例中的潜在价值,但在禁忌的情况下除外。通过测试抗生素的联合使用或新配方,该实验模型可用于为人类钩端螺旋体病确定更好的治疗策略。