Asim K. Dutt

Short-Course Chemotherapy for Extrapulmonary Tuberculosis: Nine Years' Experience

: Short-course chemotherapy with isoniazid and rifampin is well established for pulmonary tuberculosis but not yet for extrapulmonary disease. We report our 9-year experience with short-course chemotherapy in treating 350 patients; 402 extrapulmonary sites were involved. Therapy was largely self-administered with careful monitoring by local public health nurses. Administration of drugs was directly supervised in less than 2% of patients. Short-course chemotherapy with isoniazid and rifampin for 9 months was successful in 95% of patients, equivalent to conventional therapy with two to three drugs for 18 to 24 months. It was found that early drainage and complete debridement of necrotic material in bone lesions enhances healing. Short-course chemotherapy has excellent patient acceptance, short duration, fewer doses, and modest toxicity. Our largely twice-weekly regimen has the additional advantages of reduced cost, fewer doses, and ease of supervision when needed.

Tuberculosis in the elderly.

Elderly persons of today are survivors of a time when most adults were infected with tuberculosis. Although many people died at that time, others survived the initial infection but continued to harbor viable bacilli in dormant caseous and calcified lesions. This article discusses the tuberculin test in the elderly, transmission and risk of infection in nursing homes, clinical manifestations, diagnosis, management considerations, preventive therapy, and surveillance of tuberculosis in nursing homes.

Short-Course chemotherapy for tuberculosis with mainly twice-weekly isoniazid and rifampin: Community physicians' seven-year experience with mainly outpatients

The general medical community in the United States has been rather slow in adopting short-course bactericidal chemotherapy for tuberculosis despite the clear demonstration of the advantage by several carefully controlled clinical trials. Reported herein is experience between January 1976 and December 1982 in 1,028 patients with bacteriologically proved pulmonary tuberculosis treated for nine months with isoniazid (300 mg) and rifampin (600 mg) daily for one month followed by twice-weekly isoniazid (900 mg) and rifampin (600 mg) for the other eight months. They were treated by 45 local practitioners and supervised by public health nurses through 60 Arkansas Department of Health chest clinics in the state. Outpatient therapy was mostly self-administered in the routine treatment program. Overall success was achieved in 95 percent of the 751 patients who completed therapy; in 21 (2.8 percent), sputum cultures failed to convert to negative, and 15 (2.1 percent) have had relapse since therapy was stopped. Therapy could not be completed in 26.9 percent due to deaths, drug toxicities, relocation, refusal, etc. Of 21 bacteriologic failures, 18 patients developed isoniazid resistance and were treated with additional two bactericidal drugs. Most of the relapses (nine of 15) occurred within 12 months after chemotherapy was stopped. However, four relapses occurred quite late during follow-up. Only three of 15 patients with relapse showed isoniazid resistance. Side effects of the drugs were encountered in 10.3 percent, but major toxicities occurred in 3.2 percent (hepatitis in 2.6 percent, hematologic effects in 0.6 percent). Clinical surveillance for toxicity is preferred over routine and regular biochemical monitoring. Patient acceptance of the regimen was excellent, and compliance was good. Short-course chemotherapy is effective, with low drug toxicity, reduced cost of drugs, and ease of direct supervision when needed, and is acceptable to patients in routine treatment.

Theophylline kinetics in chronic obstructive airway disease in the elderly

Theophylline kinetic studies, serial spirometric function tests, and arterial blood gas determinations were performed in 39 adult men with stable chronic obstructive airway disease (COPD). Subjects were given an intravenous aminophylline loading dose of 5.6 mg/kg and a maintenance dose of 0.9 mg/kg/hr for 6 hours. Elderly (>60 years old) nonsmoking subjects had 36% lower theophylline clearance (Cl) and a 40% longer serum theophylline elimination t½ than did middle‐aged (<60 years old) nonsmoking subjects (X̄ ± SE; clearances of 32.6 ± 3.2 [n = 13] and 50.7 ± 8.5 ml/kg/hr [n = 8] and t½s of 11.0 ± 0.8 and 7.4 ± 0.8 hours, respectively). There were also differences in Cl and t½ between elderly and middle‐aged subjects in both the smoking and nonsmoking groups: elderly group, Cl = 43.6 ± 3.7 mg/kg/hr and t½ = 9.0 ± 0.7 hours; middle‐aged group, Cl = 57.6 ± 6.0 mg/kg/hr and t½ = 6.7 ± 0.6 hours). There was consistent improvement in spirometric functions in both nonsmoking and smoking elderly subjects: percent changes in forced expiratory volume in 1 second of 19% to 25%; in forced vital capacity of 25% to 31%; in forced expiratory flow at 25% to 75% of vital capacity of 59% to 67%; and in maximum mid‐flow time of −25% to −30%, at serum theophylline concentrations of 10 to 13 mg/L (group mean). We conclude that elderly nonsmoking subjects with COPD cleared theophylline more slowly than did middle‐aged, nonsmoking subjects with COPD. There was also a slight improvement in pulmonary function during theophylline dosing to maintain serum levels between 8 and 16 mg/L.

Follow-up of patients with tuberculosis treated in a general hospital program. Treatment largely as outpatients by community physicians.

As of December 1975, there had been 5 to 8 1/2 years of observation on 263 patients with bacteriologically proven tuberculosis who were initially admitted to a general hospital and were treated largely as outpatients by community physicians from July 1967 through December 1970. Ten patients died during hospitalization, and 253 were released to therapy as outpatients. Although smears or cultures of sputum remained positive at discharge in 136 (54 percent) of the 253 patients, no new infections were subsequently detected among their contacts. During initial therapy, 24 patients died of causes other than tuberculosis. Of the remaining 229 patients, the original 18-month treatment was successful in 197 (86 percent). The treatment failed initially in 11 patients, eight of whom represented relapses from previous therapy. During long-term follow-up of the 229 patients, there were only six relapses (3 percent) after the initial success. An overall rate of successful treatment of 92 percent (211/229) was achieved in the program, with 18 failures of treatment (8 percent); ie, 11 patients were lost to supervision, four died of tuberculosis, and in three, treatment was never successful.

Chemotherapy of Tuberculosis in Developed Countries

The chemotherapeutic era of tuberculosis began with the discovery of streptomycin (SM) in 1944 and its trial in 1945 (1,2). Soon after the introduction of isoniazid (INH) in 1952 (3), drug therapy was adopted as an important weapon in the treatment of this ancient disease. In the early stages of chemotherapy, it became apparent that drug resistance and treatment failure resulted when monotherapy with SM was used to treat active disease harboring large bacillary populations (4). The addition of a second drug to the regimen, such as para-amino-salicylic acid (PAS) or INH, prevented the emergence of drug resistance and treatment failure (5,6). Soon, the efficacy of chemotherapy was firmly established. Provided that the appropriate drug combinations were utilized against susceptible pretreatment organisms, tuberculosis could be cured within 18–24 months.

Follow-Up of Patients with Tuberculosis Treated in a General Hospital Program

As of December 1975, there had been 5 to 8 1/2 years of observation on 263 patients with bacteriologically proven tuberculosis who were initially admitted to a general hospital and were treated largely as outpatients by community physicians from July 1967 through December 1970. Ten patients died during hospitalization, and 253 were released to therapy as outpatients. Although smears or cultures of sputum remained positive at discharge in 136 (54 percent) of the 253 patients, no new infections were subsequently detected among their contacts. During initial therapy, 24 patients died of causes other than tuberculosis. Of the remaining 229 patients, the original 18-month treatment was successful in 197 (86 percent). The treatment failed initially in 11 patients, eight of whom represented relapses from previous therapy. During long-term follow-up of the 229 patients, there were only six relapses (3 percent) after the initial success. An overall rate of successful treatment of 92 percent (211/229) was achieved in the program, with 18 failures of treatment (8 percent); ie, 11 patients were lost to supervision, four died of tuberculosis, and in three, treatment was never successful.

Medical and Legal Aspects of Tuberculosis in Drug Addicts, Prisoners, and Patients with AIDS

Tuberculosis is an ancient infection known to mankind in all ages and in every part of the world. The causative organism Mycobacterium tuberculosis is (often referred to as the tubercle bacillus) was discovered by Robert Koch more than 100 years ago. Despite easy recognition and effective therapy, tuberculosis remains a major cause of morbidity and mortality in the developing world.

Clinical InvestigationsFollow-Up of Patients with Tuberculosis Treated in a General Hospital Program: Treatment Largely as Outpatients by Community Physicians

As of December 1975, there had been 5 to 8 1/2 years of observation on 263 patients with bacteriologically proven tuberculosis who were initially admitted to a general hospital and were treated largely as outpatients by community physicians from July 1967 through December 1970. Ten patients died during hospitalization, and 253 were released to therapy as outpatients. Although smears or cultures of sputum remained positive at discharge in 136 (54 percent) of the 253 patients, no new infections were subsequently detected among their contacts. During initial therapy, 24 patients died of causes other than tuberculosis. Of the remaining 229 patients, the original 18-month treatment was successful in 197 (86 percent). The treatment failed initially in 11 patients, eight of whom represented relapses from previous therapy. During long-term follow-up of the 229 patients, there were only six relapses (3 percent) after the initial success. An overall rate of successful treatment of 92 percent (211/229) was achieved in the program, with 18 failures of treatment (8 percent); ie, 11 patients were lost to supervision, four died of tuberculosis, and in three, treatment was never successful.