David L. Cohn, MD; Barbara J. Catlin, RN; Karen L. Peterson, MD; Franklyn N. Judson, MD; John A. Sbarbaro, MD, MPH
Study Objective: To evaluate the efficacy and toxicity of a 62-dose, four-drug, 6-month, and directly observed regimen for treatment of pulmonary and extrapulmonary tuberculosis.
Design: An open, nonblinded clinical trial, with intended follow-up of patients for 36 months after the completion of therapy.
Setting: A metropolitan tuberculosis clinic in a public health department.
Patients: From March 1981 through April 1989, we enrolled 160 patients with suspected or known tuberculosis; 35 of these patients were excluded from the analysis.
Interventions: Isoniazid, rifampin, pyrazinamide, and streptomycin were administered daily for 2 weeks; these drugs were then given in higher doses twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 18 weeks. A total of 62 doses were administered, and all therapy was directly observed by a nurse or an outreach worker.
Measurements and Main Results: Of the 125 evaluable patients, 101 (81%) had pulmonary tuberculosis, 7 (6%) had both pulmonary and extrapulmonary involvement, and 17 (13%) had extrapulmonary disease only. Seventy-one (57%) patients had a history of recent alcoholism. There were two relapses (1.6% ± 2.2%), occurring 6 and 56 months after the completion of therapy. The time at which sputum samples became culture negative in pulmonary patients ranged from 1 to 19 weeks (median, 4.6 weeks); 40% ± 9.6% of patients were culture-negative after 4 weeks of therapy, 75% ± 8.5% after 8 weeks, 94% ± 4.7% after 12 weeks, 97% ± 3.3% after 16 weeks, and 100% after 20 weeks. Adverse drug reactions included hyperuricemia (> 178 µmol/L [3 mg/dL] above normal) secondary to pyrazinamide in 80 patients (64%), twofold or greater elevations of aspartate aminotransferase in 21 patients (17%), 1.5-fold or greater elevations of alkaline phosphatase in 33 patients (27%), cutaneous abnormalities in 8 patients (6%), nausea in five patients (4%), and dizziness in 1 patient (1%).
Conclusions: This 62-dose, largely twice-weekly tuberculosis treatment regimen is efficacious and relatively nontoxic and is especially useful for patients in whom directly observed therapy is indicated.
David L. Cohn, Barbara J. Catlin, Karen L. Peterson, Franklyn N. Judson, John A. Sbarbaro. A 62-Dose, 6-Month Therapy for Pulmonary and Extrapulmonary Tuberculosis: A Twice-Weekly, Directly Observed, and Cost-Effective Regimen. Ann Intern Med. 1990;112:407–415. doi: 10.7326/0003-4819-76-3-112-6-407
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Published: Ann Intern Med. 1990;112(6):407-415.
Healthcare Delivery and Policy, Infectious Disease, Mycobacterial Infections, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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