ORIGIN AND INTERSTATE SPREAD OF A NEW-YORK-CITY MULTIDRUG-RESISTANT MYCOBACTERIUM-TUBERCULOSIS CLONE FAMILY

Objective.-To determine whether isolates of Mycobacterium tuberculosis from New York and elsewhere that are resistant to four or more primar y antimicrobial agents and responsible for widespread disease in the 1 990s represent a newly emerged clone or a heterogeneous array of unrel ated organisms. Setting.-New York City area and selected locations in the United States. Patients.-M tuberculosis isolates from 1953 patient s in New York and multidrug-resistant isolates from six patients from other US communities. Design.-Convenience sample of all M tuberculosis strains (M tuberculosis isolates resistant to rifampin, streptomycin, isoniazid, and ethambutol, and sometimes ethionamide, kanamycin, capr eomycin, or ciprofloxacin) submitted to the Public Health Research Ins titute Tuberculosis Center since 1991 and samples submitted to the Cen ters for Disease Control and Prevention from throughout the United Sta tes, The samples submitted were representative of the New York City st rains of M tuberculosis. Main Outcome Measure.-Characterization of res istant M tuberculosis strains studied by IS6110 and polymorphic CC-ric h repetitive sequence (PGRS) hybridization patterns, multiplex polymer ase chain reaction (PCR) analysis, and automated DNA sequencing of gen es containing mutations associated with resistance to rifampin (rpoB), isoniazid (katG and inhA locus), and streptomycin (strA and rrs). Res ults.-Multidrug-resistant M tuberculosis isolates were recovered from 253 New York City patients and had the same or closely allied IS6110 a nd PGRS patterns, multiplex PCR type, and gene mutations associated wi th resistance to rifampin, isoniazid, and streptomycin. Isolates with these same molecular characteristics were recovered from patients in F lorida and Nevada, health care workers in Atlanta, Ga, and Miami, Fla, and an individual who recently moved from New York City to Denver, Co le, and caused disease or skin test conversion in at least 12 people i n a nursing home environment. Conclusions.-The results document the mo lecular origin and spread of progeny of a closely related family of mu ltidrug-resistant M tuberculosis strains that have recently shared a c ommon ancestor and undergone clonal expansion. The multidrug-resistant phenotype in these organisms arose by sequential acquisition of resis tance-conferring mutations in several genes, most likely as a conseque nce of antibiotic selection of randomly occurring mutants in concert w ith inadequately treated infections. Dissemination of these difficult- to-treat bacteria throughout New York City and to at least four additi onal US cities has adverse implications for tuberculos control in the 21st century.