Resistance and susceptibility testing for Mycobacterium tuberculosis

According to the “National Action Plan to Combat Multidrug-Resistant Tuberculosis” prepared by the Centers for Disease Control (CDC), “at no time in recent history has tuberculosis (TB) been as great a concern as it is today. TB cases are on the increase and the most serious aspect of the problem is the recent occurrence of outbreaks of multidrug-resistant (MR) TB, which pose an urgent public health problem and require rapid intervention” (1). TB cases had declined in the U.S. for decades, reaching a trough in 1984 of approximately 22,000 cases (1). However, in 1985, this trend reversed, resulting in 1991 in an increase of 18.4% of cases reported to the CDC over the number reported in 1985 (2). Multiple factors contributed to the resurgence of recent TB cases. Immigration from endemic parts of the world and poverty and crowding in institutionalized populations have certainly fueled the ongoing spread of TB. Approximately 10 to 15 million Americans are estimated to be infected with TB (1). Recent reports of TB outbreaks in New York and San Francisco were related to infections with MDR strains of tuberculosis bacilli, which were resistant at least to isoniazid and rifampin, two widely used therapeutic drugs (3,4). The resistance pattern repotted for some of the MDR strains included ethambutol, streptomycin, ethionamide, kanamycin, and rifobutin. rendering anti-tuberculous therapy futile. The epidemiological situation in the U.S. is characterized by two superimposed patterns. In rural and nonmetropolitan areas, most active cases of TB are believed to result 6om reactivations of foci acquired years or decades ago. This epidemiological pathway of reactivation was thought to account for most of the cases of active TB in the U.S. However, recent studies indicate that in environments such as New York City or San Francisco, a third or more of the newly discovered active cases result from recent person-to-person transmission rather than from the reactivation of recent infection (5). Two studies used restriction-fragment-length polymorphisms (RFLP) to demonstrate the relative contribution of recent infection to the overall incidence of TB and found that at least 33% of current cases can be attributed to new infections (3.4). The source cases were highly infectious and occasionally responsible for several newly diagnosed cases. These insights obtained by DNA fingerprinting techniques make it imperative to recognize these highly contagious source cases of infection and disease (5). Adequate therapy can be administered only on the basis of results of the susceptibility testing of a given strain of Mycobacterium tuberculosis. In New York City, improved treatment by increasing the number of patients with directly observed therapy (DOT) resulted in a decrease of 15% of-new cases in 1993, which also reversed the national trend of incidence of TB for the tirst time since 1984. For many of the HIV-mfected patients, co-infection with an NMRstrainofTBwaslethal(71 to 89%), and the median time between diagnosis and death was short (4 to 16 weeks) (6). Unfortunately, this time span is equivalent to applying *conventional methods to establish the diagnosis of an infection with a slow-growing