A Pilot Study of Methodology to Rapidly Evaluate Drugs for Bactericidal Activity, Tolerance, and Pharmacokinetics in the Treatment of Pulmonary Tuberculosis Using Isoniazid and Levofloxacin

Inclusion Criteria

Concurrent Medication:

Allowed in all patients:

• Antacids if administered more than 2 hours before or after study drug.

Allowed in isoniazid patients:

• Anticonvulsant therapy if blood levels are monitored.

Allowed in levofloxacin patients:

• Acceptable medications other than antacids if administered at least 2 hours before or 1 hour after study drug.
• Anticonvulsant therapy, theophylline, or warfarin if doses are monitored.

Patients must have:

• Presumptive active pulmonary TB.
• No clinical evidence of central nervous system or miliary tuberculosis.

NOTE:

• Both HIV-positive and HIV-negative patients are eligible.

NOTE:

• Pregnant women may be enrolled in the isoniazid cohort only.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Active or suspected MAI infection.
• Active or suspected hepatitis.
• Any other serious acute infection, diabetes, chronic obstructive pulmonary disease, malignancy requiring chemotherapy, or major organ dysfunction.
• Extreme illness or toxic appearance.
• Pregnancy (if entering the levofloxacin portion of the study).

Concurrent Medication:

Excluded:

• All standard TB therapies.
• Clofazimine.
• Rifabutin.
• Quinolones.
• Aminoglycosides.
• Corticosteroids.
• Pentoxifylline.
• Colony-stimulating factors.
• Interferons.
• Interleukins.
• Disulfiram (patients receiving isoniazid).

Patients with the following prior conditions are excluded:

• History of treatment-limiting intolerance or known hypersensitivity to isoniazid (in patients receiving isoniazid) or to quinolones (in patients receiving levofloxacin).
• Vomiting or diarrhea >= grade 2 at screening or within 2 days prior to screening.
• History of drug-resistant TB (in patients receiving isoniazid).

Prior Medication:

Excluded:

• Any prior treatment or prophylaxis for TB if enrolling on the isoniazid cohort.
• Any anti-TB drug within the past 12 weeks, including standard drugs against TB as well as clofazimine, rifabutin, and all quinolones and aminoglycosides.
• Corticosteroids, pentoxifylline, colony-stimulating factors, interferons, or interleukins within the past 12 weeks.

Known risk factors for multi-drug resistant (MDR) TB, including:

• Domicile, shelter, or prison exposure to a known case of MDR TB within the past 6 months.
• Residence in a specific domicile, shelter, or prison cell block within 6 months of a known outbreak of MDR TB.
• Hospitalization, within the past 6 months, on a medical service or unit in which nosocomial transmission of MDR TB is known to have occurred.