Efficacy and Safety of Levofloxacin for the Treatment of MDR-TB

Inclusion Criteria

• Patients with smear-positive, culture positive* pulmonary TB
• Sputum contains isoniazid* and rifampin-resistant, Ofloxacin-susceptible MTB, all by MTBDR-sl
• Previously treated or newly diagnosed with tuberculosis
• Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 3 months prior to enrollment.
• Age ≥ 18 years.
• Weight > 40 Kg
• Karnofsky score of > 60 (see section 18.1)
• Willingness by the patient to attend scheduled follow-up visits and undergo study assessments.
• Women with child-bearing potential must agree to use birth control if you are having sex with men while participating in this study and for three months afterward.
• Laboratory parameters (performed within 14 days prior to enrollment):
• Estimated Serum creatinine clearance should be 1000/ mm3
• Negative pregnancy test (for women of childbearing potential) within 14 days of enrollment
• HIV viral load and CD4 count if HIV infected (within 3 months)
• Serum ALT and total bilirubin <3 times upper limit of normal
• Able to provide informed consent

Note: *Subjects may be enrolled on the basis of a presumption that they will be culture positive at either screening or baseline if they are smear-positive, but they will be excluded from the analysis if cultures are subsequently negative. This will not be deemed a protocol violation. Similarly, subjects with rifampin susceptibility on a DNA-based test may be enrolled on the basis of a presumption that they will also be INH-resistant, but they will be excluded from the analysis if the isolate is subsequently shown to be INH-susceptible. This will also not be deemed a protocol violation.

Exclusion Criteria

• Currently breast-feeding or pregnant.
• Known allergy or intolerance to or toxicity from fluoroquinolones or other medications utilized in this study.
• In the judgment of the physician the patient is not expected to survive for 6 months
• Anticipated surgical intervention for the treatment of pulmonary tuberculosis
• Participation in another investigational drug trial within the past 30 days
• Concurrent use of known QT-prolonging drugs: a list of such medications can be found at http://www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm
• Poorly controlled diabetes
• Known g-6-phosphate dehydrogenase deficiency
• Use of quinolone for 7 days within past 30 days
• QTc interval greater than 450 msec for men or greater than 470 msec for women