A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDRTB) in HIV-Infected Patients.
A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDRTB) in HIV-Infected Patients.
To determine the demographic, behavioral, clinical, and geographic risk factors associated
 with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the
 clinical and microbiological responses and overall survival of MDRTB patients who are treated
 with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per
 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of
 patients who show failure or relapse are due to the same strain or reinfection with a new
 strain.

 Among TB patients, there has been an increase in progressive disease due to the emergence of
 antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify
 patients at high risk for MDRTB increases the hazard for both treatment failure and
 development of resistance to additional therapeutic agents. Efforts to improve survival in
 patients with MDRTB will depend on improved methods of assessing the risk of acquisition of
 MDRTB and identifying drug susceptibility patterns in a timely fashion.
Among TB patients, there has been an increase in progressive disease due to the emergence of
 antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify
 patients at high risk for MDRTB increases the hazard for both treatment failure and
 development of resistance to additional therapeutic agents. Efforts to improve survival in
 patients with MDRTB will depend on improved methods of assessing the risk of acquisition of
 MDRTB and identifying drug susceptibility patterns in a timely fashion.

 Patients are asked a series of questions to determine epidemiologic factors that may be
 predictive of MDRTB. Patients who are determined to be at low risk for MDRTB will be referred
 to another TB treatment protocol (ACTG 222), if appropriate. Patients suspected of having
 primary or acquired MDRTB or those with confirmed MDRTB will be offered a regimen of anti-TB
 therapy from a hierarchically ordered list of drugs, based on the patient's resistance status
 (suspect primary MDRTB, suspect acquired MDRTB, or confirmed MDRTB). The hierarchical list is
 as follows: isoniazid, rifampin, ethambutol, streptomycin, levofloxacin, ethionamide,
 cycloserine, capreomycin, aminosalicylic acid, and clofazimine. Treatment will be
 administered daily for at least 6 months, then on an intermittent schedule at the clinician's
 discretion. Patients with confirmed MDRTB (defined as known resistance to at least isoniazid
 and rifampin within 6 months prior to study entry) will receive a minimum of 18 months of
 treatment following sputum culture conversion. Follow-up is performed every 4 weeks for 8
 weeks, and then every 8 weeks.
Inclusion Criteria

 Patients must have:

 -  Working diagnosis of HIV infection.

 -  Working diagnosis of pulmonary TB.

 Per 08/02/94 amendment, patients with confirmed MDRTB or known susceptibilities for the
 current episode at baseline are not eligible for the epidemiologic study only.

 FOR TREATMENT PILOT:

 -  Positive sputum AFB smear (or a positive sputum culture for TB within 6 months prior
 to study entry).

 -  Assessment of suspect primary, suspect acquired, AND/OR confirmed MDRTB.

 -  Life expectancy of at least 2 weeks.

 -  Age >= 18 years for suspect MDRTB. Age >= 13 years for confirmed MDRTB.

 Exclusion Criteria

 Co-existing Condition:

 Patients with the following symptoms or conditions are excluded:

 -  Known hypersensitivity or resistance to quinolones.

 -  Other disorders or conditions for which the study drugs are contraindicated.

 Prior Medication:

 Excluded:

 -  More than 6 weeks total therapy within 3 months prior to study entry using three or
 more drugs effective against the isolates. (Per 08/02/94 amendment, patients from
 protocol ACTG 222/CPCRA 019 who have MDRTB are eligible for rollover to this study
 regardless of treatment duration on ACTG 222/CPCRA 019.)