In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis.
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.
JI
B
B
Bactériologie et Virologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Lounis
N
N
Truffot-Pernot
C
C
Grosset
J
J
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D007536:Isomerism; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D064704:Levofloxacin; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D013163:Splenomegaly / Q000188:drug therapy / Q000382:microbiology; D015996:Survival Rate; D014376:Tuberculosis / Q000188:drug therapy / Q000401:mortality
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D015363:Quinolones; D064704:Levofloxacin; D015242:Ofloxacin; C061363:sparfloxacin; D007538:Isoniazid