Levy L, Peters J H
Antimicrob Agents Chemother. 1976 Jan;9(1):102-12. doi: 10.1128/AAC.9.1.102.
In the course of a clinical trial of acedapsone therapy in 17 patients with lepromatous leprosy, the rate of response to therapy was measured by inoculation of mice with Mycobacterium leprae recovered from biopsy specimens of skin lesions obtained before treatment and at intervals of 4, 12, and 24 weeks after institution of treatment. The susceptibility of each isolate of M. leprae to dapsone (4,4'-diaminodiphenylsulfone [DDS]) was measured by passaging organisms that had multiplied in mice to new groups of untreated mice and to mice treated with DDS incorporated in the mouse chow in concentrations of 10(-5), 3 x 10(-5), and 10(-4) g/100 ml. The rate of response to acedapsone therapy and the susceptibility of patient strains of M. leprae to DDS varied widely among patients. All isolates were inhibited from multiplication by treatment of mice with 10(-4) g of DDS per 100 ml; all but two isolates were susceptible to 3 x 10(-5) g of DDS per 100 ml; and 17 of 36 isolates, representing nine patient strains, were susceptible to 10(-5) g of DDS per 100 ml. Plasma levels of DDS measured in the mice administered these diets show that the minimal inhibitory concentration of DDS for M. leprae isolated from untreated patients is about 3 ng/ml. No relationship could be demonstrated between DDS susceptibility of pretreatment isolates of M. leprae and the rate at which patients responded to acedapsone therapy. Neither acedapsone treatment of patients nor DDS treatment of mice appeared to select genotypically more resistant M. leprae.
在一项针对17例瘤型麻风患者的醋氨苯砜治疗临床试验过程中，通过用从治疗前及治疗开始后4周、12周和24周获取的皮肤病变活检标本中分离出的麻风分枝杆菌接种小鼠，来测定治疗反应率。通过将在小鼠体内繁殖的麻风分枝杆菌接种到新的未治疗小鼠组以及用含10⁻⁵、3×10⁻⁵和10⁻⁴ g/100 ml浓度的氨苯砜（4,4'-二氨基二苯砜[DDS]）掺入小鼠饲料中进行治疗的小鼠组，来测定每株麻风分枝杆菌对氨苯砜的敏感性。患者对醋氨苯砜治疗的反应率以及患者麻风分枝杆菌菌株对DDS的敏感性在患者之间差异很大。用每100 ml含10⁻⁴ g DDS治疗小鼠可抑制所有分离株的繁殖；除两株分离株外，所有分离株对每100 ml含3×10⁻⁵ g DDS敏感；36株分离株中的17株（代表9个患者菌株）对每100 ml含10⁻⁵ g DDS敏感。在给予这些饲料的小鼠中测得的DDS血浆水平表明，从未治疗患者分离出的麻风分枝杆菌对DDS的最低抑菌浓度约为3 ng/ml。治疗前麻风分枝杆菌分离株的DDS敏感性与患者对醋氨苯砜治疗的反应率之间未显示出相关性。对患者进行醋氨苯砜治疗或对小鼠进行DDS治疗似乎都未选择出基因型上更具抗性的麻风分枝杆菌。
