A MULTIINSTITUTIONAL OUTBREAK OF HIGHLY DRUG-RESISTANT TUBERCULOSIS -EPIDEMIOLOGY AND CLINICAL OUTCOMES

Objective.-To investigate a multi-institutional outbreak of highly res istant tuberculosis and evaluate patient outcome. Design.-Epidemiologi c investigation of every tuberculosis case reported in New York City. Setting.-Patients cared for at all public and nonpublic institutions f rom January 1, 1990, to August 1, 1993 (43 months). Patients.-We revie wed medical and public health records and conducted clinical, epidemio logic, drug susceptibility, and restriction fragment length polymorphi sm (RFLP) analyses. A case was defined as tuberculosis in a patient wi th an isolate resistant to isoniazid, rifampin, ethambutol hydrochlori de, and streptomycin (and rifabutin, if sensitivity testing included i t), and, if RFLP testing was done, a pattern identical to or closely r elated to strain W. Main Outcome Measures.-Patient survival and the co nversion of sputum cultures from positive to negative. Results.-Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% ha d unknown HIV status. All-cause mortality was 83%. Epidemiologic linka ges were identified for 70% of patients, of whom 96% likely had nosoco mially acquired disease at 11 hospitals. Survival was prolonged among patients who recieved medications to which their isolate was susceptib le, especially capreomycin sulfate, and among patients with a CD4(+) T -lymphocyte count greater than 0.200x10(9)/L (200/mu L). Treatment wit h isoniazid and a fluoroquinolone antibiotic was also independently as sociated with longer survival. Conclusions.-This outbreak accounted fo r nearly one fourth of the cases of multidrug-resistant tuberculosis i n the United States during a 43-month period. Most patients had nosoco mially acquired disease, were infected with HIV, and unless promptly a nd appropriately treated, died rapidly. With appropriate directly obse rved treatment, especially combinations including an injectable medica tion, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.