Results at 30 months of a randomised trial of FDCs and separate drugs for the treatment of tuberculosis.

Study C was an open-label, non-inferiority, randomised controlled trial of fixed-dose combination (FDC) or separate drugs given during the intensive phase of treatment to 1585 patients with smear-positive pulmonary tuberculosis conducted at 11 sites in Africa, Asia and Latin America. Thirty months post-randomisation, the failure/relapse rates in the per protocol population were 7.4% of 591 patients on FDCs and 6.5% of 587 patients on separate drugs; the site-adjusted difference was 0.3% (90%CI -1.8 to 2.3). In the modified intention-to-treat analysis, the corresponding results were respectively 17.9% of 683 and 16.1% of 671; the site-adjusted difference was 2.0% (90%CI -1.2 to 5.2).

Rates and risk factors for discontinuation of rifampicin.

SETTING: All patients with culture-confirmed, rifampin-susceptible Mycobacterium tuberculosis diagnosed during a 20-month period in New York City, who were started on a rifampin-containing regimen and received > or =60 days of treatment. OBJECTIVE: To identify rates of and reasons for rifampin discontinuation. DESIGN: Retrospective case-control study using surveillance data and medical record reviews. Discontinuation due to thrombocytopenia, creatinine >2.0 mg/dl, bilirubin >2.0 mg/dl or severe reactions (generalized rash, persistent drug fever, or severe interference with methadone metabolism) were defined as appropriate for discontinuation of rifampin. All other reactions were classified as inappropriate. RESULTS: Of 3,520 patients, rifampin was discontinued in 68 (1.9%); of these, 57% had rifampin discontinued unnecessarily. Treatment by an inexperienced provider (adjusted odds ratio [ORadj] 4.0; 95% confidence interval [CI] 1.9-8.5), race (ORadj 3.1; 95%CI 1.4-6.9), history of previous treatment (ORadj 4.8; 95%CI 1.9-12.5), and history of methadone drug treatment (ORadj 12.6; 95%CI 5.3-29.9) were all associated with inappropriate rifampin discontinuation. CONCLUSION: True intolerance was rare, even among those patients infected with the human immunodeficiency virus. Most patients with minor reactions can successfully complete treatment with rifampin, particularly if managed by a physician experienced in the treatment of tuberculosis.

Patient and health care system delays in the diagnosis and treatment of tuberculosis.

SETTING: All culture-positive tuberculosis patients without previous treatment for tuberculosis (n = 184), New York City, April 1994. OBJECTIVE: To examine factors associated with delays in presenting to a health care provider (patient delay) and in starting antituberculosis treatment (health care system delay). DESIGN: Retrospective medical record review and patient interviews. RESULTS: Median total delay was 57 days (range 4-764), 35 for acid-fast bacilli smear-positive patients and 79 for smear-negative patients (P < 0.001). Median patient delay was 25 (range 0-731). Median health care system delay was 15 days, 6 for smear-positive patients and 31 for smear-negative patients (P < 0.001). In logistic regression, age 55-64 years (adjusted odds ratio [OR(adj)] 10.6, 95% confidence interval [CI] 1.3-86.9), and primary language other than English (OR(adj) 2.5, 95%CI 1.0-5.8), were associated with longer patient delays. Homelessness (OR(adj) 7.1, 95%CI 1.05-33.5), not having a chest radiograph at the first medical visit (OR(adj) 2.4, 95%CI 1.0-5.4), negative smear (OR(adj) 10.2, 95%CI 4.4-23.3) and absence of cough (OR(adj) 2.9, 95%CI 1.2-6.8) were associated with longer health care system delays. CONCLUSION: To reduce delays, patients should be educated to seek care more quickly, and should be provided with culturally appropriate health care and language services. Physicians should maintain a high index of suspicion for tuberculosis and perform appropriate diagnostic tests.

A continuing survey of drug-resistant tuberculosis, New York City, April 1994.

BACKGROUND: A 1991 survey showed high levels of drug resistance among tuberculosis patients in New York, NY. As a result, the tuberculosis control program was strengthened, including expanded use of directly observed therapy and improved infection control. METHODS: We collected isolates from every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1994; results were compared with those in the April 1991 survey. RESULTS: From 1991 to 1994, the number of patients decreased from 466 to 332 patients. The percentage with isolates resistant to 1 or more antituberculosis drugs decreased from 33% to 24% (P < .01); with isolates resistant to at least isoniazid decreased from 26% to 18% (P < .05); and with isolates resistant to both isoniazid and rifampin decreased from 19% to 13% (P < .05). The number of patients with isolates resistant to both isoniazid and rifampin decreased by more than 50%. Among never previously treated patients, the percentage with resistance to 1 or more drugs decreased from 22% in 1991 to 13% in 1994 (P < .05). The number of patients with consistently positive culture results for more than 4 months decreased from 130 to 44. A history of antituberculosis treatment was the strongest predictor of drug resistance (odds ratio = 3.1; P < .001). Human immunodeficiency virus infection was associated with drug resistance among patients who never had been treated for tuberculosis. CONCLUSIONS: Drug-resistant tuberculosis declined significantly in New York City from 1991 to 1994. Measures to control and prevent tuberculosis were associated with a 29% decrease in the proportion of drug resistance and a 52% decrease in the number of patients with multidrug-resistant tuberculosis.