A total of 217 specimens submitted for routine smear and culture from three different sites within the western United States were used to evaluate the GeneXpert MTB/RIF assay (for research use only) (Cepheid, Sunnyvale, CA). Overall agreement compared to culture was 89% (98% for smear positives and 72% for smear negatives) for detection of Mycobacterium tuberculosis.

Chemotherapy of tuberculosis caused by multiple-drug-resistant (MDR) strains is problematic because of choices limited to relatively inefficacious and toxic drugs. Some beta-lactam antibiotics are active against Mycobacterium tuberculosis in vitro. We investigated the efficacy of imipenem in a mouse model of tuberculosis and in humans with MDR tuberculosis. Mice infected with M. tuberculosis strain H37Rv were treated with isoniazid or imipenem. Residual organisms in lung and spleen and survival of imipenem-treated mice were compared to those of untreated or isoniazid-treated mice. Ten patients with MDR tuberculosis also were treated with imipenem in combination with other first-or second-line agents; elimination of M. tuberculosis from sputum samples was measured by quantitative culture. Although it was less effective than isoniazid, imipenem significantly reduced the numbers of M. tuberculosis organisms in lungs and spleens and improved survival of mice. Eight of 10 patients with numerous risk factors for poor outcomes responded to imipenem combination therapy with conversion of cultures to negative. Seven remained culture-negative off of therapy. There were two deaths, one of which was due to active tuberculosis. Organisms were eliminated from the sputa of responders at a rate of 0.35 log 10 CFU/ml/week. Relapse upon withdrawal of imipenem and development of resistance to imipenem in a nonresponder suggest that imipenem exerts antimycobacterial activity in humans infected with M. tuberculosis. Imipenem had antimycobacterial activity both in a mouse model and in humans at high risk for failure of treatment for MDR tuberculosis.Treatment of tuberculosis caused by multiple-drug-resistant (MDR) (i.e., resistant to both isoniazid [INH] and rifampin) strains of Mycobacterium tuberculosis (MDR TB) is a challenge. Second-line antituberculous agents are less efficacious and more toxic than first-line drugs (5, 13). Fluoroquinolones, which can significantly improve response rates, are an important recent addition to the therapeutic armamentarium (13, 17), but other alternatives are desperately needed.Beta-lactams have not been regarded as useful drugs for treatment of tuberculosis because M. tuberculosis is naturally resistant to most of these antibiotics in vitro. Resistance is thought to be mediated by a class A beta-lactamase that hydrolyzes penicillins and cephalosporins (4,6,8). Resistance may be overcome by two means. One is inhibition of the beta-lactamase, and the other is the use of an antibiotic that is not a substrate for it. An example of the former is the use of the beta-lactam-beta-lactamase inhibitor combination amoxicillin-clavulanate, which is active in vitro (3) and has early bactericidal activity in patients with pulmonary tuberculosis (1). Anecdotally, amoxicillin-clavulanate in combination with other second-line agents has been successfully used in selected patients infected with MDR strains (11,19). This approach has met considerable skepticism, and the role, if any, of amoxicillin-clavulanate rem...

Education or the promise of an incentive improved initial follow-up. Education was superior to an incentive for the completion of therapy. Fairly modest strategies provided in jail can improve adherence. Further links between jail health services and community care should be explored.

These results suggest that plasma ET-1 is related to diabetic microvascular disease.