Multidrug-resistant tuberculosis in patients without HIV infection.

Background. Investigations of outbreaks of multidrug-resistant tuberculosis have found low rates of treatment response and very high mortality, and they have mainly involved patients with advanced human immunodeficiency virus (HIV) infection. For patients without HIV infection, one study reported an overall rate of response to treatment of 56 percent, and the mortality from tuberculosis was 22 percent. We investigated treatment response and mortality rates in 26 HIV-negative patients in New York with multidrug-resistant tuberculosis. Methods. We obtained detailed data from seven teaching hospitals in New York City on patients with multidrug-resistant tuberculosis — defined as tuberculosis resistant at least to isoniazid and rifampin — who were HIV-negative on serologic testing. Lengths of times from diagnosis to the initiation of appropriate therapy and from the initiation of appropriate therapy to conversion to negative cultures were assessed. Therapeutic responses were evaluated by both microbiologic and clinical criteria. Results. Between March 1991 and September 1994, 26 HIV-negative patients were identified and treated. Of the 25 patients for whom adequate data were available for analysis, 24 (96 percent) had clinical responses; all 17 patients for whom data on microbiologic response were available had such a response. The median times from diagnosis to the initiation of appropriate therapy and from the initiation of therapy to culture conversion were 44 days (range, 0 to 181) and 69 days (range, 2 to 705), respectively. Side effects requiring the discontinuation of medication occurred in 4 of 23 patients (17 percent) who were treated with second-line antituberculosis medications. The median follow-up for the 23 patients who responded and who received appropriate therapy was 91 weeks (range, 41 to 225). Conclusions. In this report from New York City, HIVnegative patients with multidrug-resistant tuberculosis, contrary to previous reports, responded well to appropriate chemotherapy, both clinically and microbiologically. (N Engl J Med 1995;333:907-11.) From the Bronx–Lebanon Hospital Center, Bronx, N.Y. (E.E.T., S.B., G.T.); St. Clare’s Hospital and Health Center, New York (K.S.); New York Hospital–Cornell Medical Center, New York (K.S., S.M.); Harlem Hospital Center, New York (F.M., W.E.-S.); Montefiore Medical Center and North Central Bronx Hospital, Bronx, N.Y. (P.A.); St. Vincent’s Medical Center, New York (A.G.); and Beth Israel Medical Center, New York (N.S.). Address reprint requests to Dr. Telzak at the Division of Infectious Diseases, Bronx–Lebanon Hospital Center, Albert Einstein College of Medicine, 1650 Grand Concourse, Bronx, NY 10457. T HE emergence of multidrug-resistant tuberculosis has been well documented in both New York City and the rest of the United States. 1-3 Though New York City had the highest rate in a national survey of reported tuberculosis cases in the first quarter of 1991, cases of multidrug-resistant tuberculosis were reported from 13 states and 35 of the nation’s counties (1.1 percent). 3 Previous studies have found that patients with drugresistant tuberculosis have lower response rates than patients with drug-susceptible isolates. 4,5 Recent investigations of outbreaks of multidrug-resistant tuberculosis have found an extraordinarily high case fatality rate, with the median mortality being reached between 4 and 16 weeks. 6-9 In almost all instances, these outbreaks have involved patients severely immunosuppressed by infection with the human immunodeficiency virus (HIV). More recent data suggest that outcomes can be improved if patients promptly start to receive two or more drugs that have in vitro activity against the multidrug-resistant isolates. 10-12 The expected outcome in patients not infected with HIV who have multidrug-resistant tuberculosis is less well defined. However, a widely cited study of 171 HIVnegative patients treated from 1973 to 1983 at the National Jewish Center for Immunology and Respiratory Medicine found an overall response rate of 56 percent and a mortality rate attributable to tuberculosis of 22 percent. 13 In New York City, because of the recent dramatic increase in cases of tuberculosis and multidrug-resistant tuberculosis, we have had the opportunity to evaluate patients with multidrug-resistant tuberculosis who are not HIV-infected. We describe our experience with 25 patients whose clinical characteristics and outcomes differed dramatically from those of previously published studies.