JI B, Lounis N, Truffot-Pernot C, Grosset J
Bactériologie et Virologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Antimicrob Agents Chemother. 1995 Jun;39(6):1341-4. doi: 10.1128/AAC.39.6.1341.
In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but the MICs at which 90% of the strains are inhibited were similar. The in vivo activity of LVFX against M. tuberculosis was compared with the activities of isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with 1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out six times weekly for 4 weeks. The severity of infection and effectiveness of treatment were assessed by survival rate, spleen weights, gross lung lesions, and enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti-M. tuberculosis activities of the treatments used ran in the following order: LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg) > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It seems, therefore, that the in vivo activity of LVFX is comparable to that produced by a twofold-greater dosage of OFLO. It is assumed that the maximal clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX displayed powerful bactericidal activity, promising effects against human tuberculosis may be achieved if patients are treated with the maximal clinically tolerated dosage of LVFX.
在对18株药物敏感的结核分枝杆菌菌株进行的试验中，左氧氟沙星（LVFX）抑制50%菌株生长的最低抑菌浓度（MIC）比氧氟沙星（OFLO）抑制50%菌株生长的MIC低一个稀释度，但抑制90%菌株生长的MIC相似。将LVFX对结核分枝杆菌的体内活性与异烟肼、OFLO和司帕沙星（SPFX）的活性进行了比较。给小鼠静脉接种1.74×10⁶CFU的H37Rv，次日开始治疗，每周进行6次，持续4周。通过存活率、脾脏重量、肺部大体病变以及脾脏中CFU的计数来评估感染的严重程度和治疗效果。就CFU计数而言，所用治疗方法抗结核分枝杆菌活性的排名如下：LVFX（300mg/kg体重）=SPFX（10mg/kg）>异烟肼>SPFX（50mg/kg）>OFLO（300mg/kg）=LVFX（150mg/kg）>OFLO（150mg/kg）=LVFX（50mg/kg）。因此，LVFX的体内活性似乎与两倍剂量OFLO产生的活性相当。假定LVFX的最大临床耐受剂量与OFLO相似，即每日800mg，相当于小鼠每千克体重300mg的LVFX。由于LVFX显示出强大的杀菌活性，如果用LVFX的最大临床耐受剂量治疗患者，可能会对人类结核病产生有前景的疗效。
