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Diagnostic difficulties arise when sputum smears are negative for acid-fast bacilli in tuberculin-positive patients with compatible symptoms and chest radiographs for tuberculosis. Many of these smear-negative patients yield positive cultures for M tuberculosis, whereas others remain culturally negative. Several studies have shown that many smear-negative/culture-negative patients will develop bacteriologically positive disease later. Often, physicians are unable to decide whether to initiate chemotherapy or to wait for the culture results. Also, if treatment is initiated in smear negative patients, what should be the drug regimen and duration of therapy. A positive smear signifies a very large bacterial population in the lung lesions whereas several negative smears suggest a smaller bacterial load. Such smear-negative cases do not require the same intensity and duration of treatment as smear-positive cases. Therapy should be initiated for tuberculosis after other causes for abnormal chest x-ray have been excluded. However, duration of therapy may be shortened in these cases. The British Medical Research Council (BMRC) study has shown that intensive treatment of smear-negative/culture-positive disease with streptomycin (SM), isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) for 4 months was uniformly successful. This regimen is routinely recommended in Hong Kong. Because primary drug resistance is low (< 3%) in Arkansas, we treated these cases with INH and RIF for 6 months with good results. This is now a routine drug regimen. For smear-negative/culture-negative cases, the BMRC study has shown that daily or thrice weekly treatment with SM, INH, RIF, and PZA for 4 months is effective.(ABSTRACT TRUNCATED AT 250 WORDS)

The duration of therapy for pulmonary tuberculosis (TB) is now shortened to 6 or 9 months with the use of bactericidal drugs. There are few reports on the results of short course chemotherapy (SCC) in extrapulmonary tuberculosis (EP). It is unlikely that many controlled studies shall be forthcoming in the future because of involvement of many sites with the disease, each of which has special problems. However, available controlled studies and clinical experiences in EP indicate early success. The site of the disease appears to be less important since the bacterial population is much smaller in EP than in TB and is easily amenable to the bactericidal drugs. Present bactericidal drugs (isoniazid [INH], rifampin [RIF], pyrazinamide [PZA]) penetrate well into tissues and attain bactericidal levels to kill the organisms. Our experience with 9-month SCC consisting of INH 300 mg and RIF 600 mg daily for one month, followed by INH 900 mg and RIF 600 mg twice weekly for another 8 months in 478 cases of EP showed overall success in over 95% of those patients who completed therapy over a median follow-up of 42 months. The drugs may be given daily throughout with the same success. Thus, 9-month therapy with INH and RIF is highly effective in EP due to drug sensitive organisms. In TB, the duration may be shortened to 6-months with initial intensive four-drug therapy consisting of INH, RIF, PZA and streptomycin (SM) or ethambutol (EMB) daily for 2 months, followed by INH and RIF daily or twice weekly for another 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)