In this outbreak of tuberculosis, the growth characteristics of the strain involved greatly exceeded those of other clinical isolates of M. tuberculosis. The extensive transmission of tuberculosis may have been due to the increased virulence of the strain rather than to environmental factors or patient characteristics.
In addition to basic TB control measures, elimination strategies should include targeted evaluation and treatment of individuals in high-prevalence groups, as well as enhanced support for global TB prevention and control.
Background. We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum.Methods. Adults participated if they had a history of cough у2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for 17 days. Observed maximum serum concentrations were compared with published normal ranges.Results. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have 14 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels ( for all). The associations with noncavitary pulmonary disease ( ) and HIV infection ( P ! .05 P p .12 P p ) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by .07 rifampin.Conclusions. These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.
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