Kazragis R J, Dever L L, Jorgensen J H, Barbour A G
Department of Medicine (Infectious Diseases), University of Texas Health Science Center at San Antonio 78284, USA.
Antimicrob Agents Chemother. 1996 Nov;40(11):2632-6. doi: 10.1128/AAC.40.11.2632.
Borrelia burgdorferi, the agent of Lyme disease, and B. turicatae, a neurotropic agent of relapsing fever, are susceptible to vancomycin in vitro, with an MIC of 0.5 microgram/ml. To determine the activity of vancomycin in vivo, particularly in the brain, we infected adult immunocompetent BALB/c and immunodeficient CB-17 scid mice with B. burgdorferi or B. turicatae. The mice were then treated with vancomycin, ceftriaxone as a positive control, or normal saline as a negative control. The effectiveness of treatment was assessed by cultures of blood and brain and other tissues. Ceftriaxone at a dose of 25 mg/kg of body weight administered every 12 h for 7 to 10 days eliminated cultivable B. burgdorferi or B. turicatae from all BALB/c or scid mice in the study. Vancomycin at 30 mg/kg administered every 12 h was effective in eliminating infection from immunodeficient mice if treatment was started within 3 days of the onset of infection. If treatment with vancomycin was delayed for 7 days or more, vancomycin failed to eradicate infection with B. burgdorferi or B. turicatae from immunodeficient mice. The failure of vancomycin in eradicating established infections in immunodeficient mice was associated with the persistence of viable spirochetes in the brain during antibiotic treatment.
莱姆病病原体伯氏疏螺旋体(Borrelia burgdorferi)以及回归热的嗜神经病原体土拉疏螺旋体(B. turicatae)在体外对万古霉素敏感,其最低抑菌浓度(MIC)为0.5微克/毫升。为确定万古霉素在体内尤其是在脑内的活性,我们用伯氏疏螺旋体或土拉疏螺旋体感染成年免疫功能正常的BALB/c小鼠和免疫缺陷的CB-17 scid小鼠。然后给小鼠分别用万古霉素、作为阳性对照的头孢曲松或作为阴性对照的生理盐水进行治疗。通过对血液、脑及其他组织进行培养来评估治疗效果。以25毫克/千克体重的剂量每12小时给予头孢曲松,持续7至10天,可使研究中的所有BALB/c或scid小鼠体内可培养的伯氏疏螺旋体或土拉疏螺旋体消失。如果在感染开始后3天内开始治疗,每12小时给予30毫克/千克的万古霉素可有效消除免疫缺陷小鼠体内的感染。如果万古霉素治疗延迟7天或更长时间,则无法根除免疫缺陷小鼠体内的伯氏疏螺旋体或土拉疏螺旋体感染。万古霉素无法根除免疫缺陷小鼠体内已确立的感染,这与抗生素治疗期间脑内存活螺旋体的持续存在有关。