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Maria de Lourdes García-García, MD, DrSc; Alfredo Ponce-de-León, MD; Maria Eugenia Jiménez-Corona, MD; Aída Jiménez-Corona, MD, MSc; Manuel Palacios-Martínez, MD; Susana Balandrano-Campos, BA; Leticia Ferreyra-Reyes, MD; Luis Juárez-Sandino, CT; José Sifuentes-Osornio, MD; Hiram Olivera-Díaz, MSc; José Luis Valdespino-Gómez, MD, MPH; Peter M. Small, MD

Arch Intern Med. 2000;160:630-636.

Background  Consequences of drug-resistant tuberculosis (TB) in developing countries using directly observed treatment, short-course (DOTS), are not well defined.

Objective  To determine the impact of drug resistance on clinical outcome and transmission of TB under programmatic conditions.

Patients and Methods  A prospective cohort and molecular epidemiologic study was conducted in southern Mexico. Between March 1995 and February 1998 all patients with persistent cough whose sputa had acid-fast bacilli (AFB) underwent clinical and mycobacteriologic evaluation (species identification, drug susceptibility testing, and IS6110-based genotyping). Treatment was provided in accordance with Mexico's National Tuberculosis Program. Clinical and microbiologic outcomes and molecular epidemiologically defined transmission were measured.

Results  Mycobacterium tuberculosis was isolated from 238 of the 284 AFB smear–positive persons. The overall rate of resistance was 28.4% (new, 20.7%; retreated, 54.7%), and 10.8% (new, 3.3%; retreated, 35.8%) had multi–drug-resistant TB (ie, resistance to isoniazid and rifampin). After treatment, 75% (new, 81.0%; retreated, 52.8%) were cured, 8% (new, 7.8%; retreated, 7.5%) abandoned therapy, 9% (new, 3.9%; retreated, 28.3%) had treatment failure, and 4% (new, 3.3%; retreated, 7.5%) died. Another 2% of patients relapsed, and 9% died during a median of 24.4 months of follow-up. Drug-resistance was a strong independent risk factor for treatment failure. Being infected with multi–drug-resistant TB was the only factor associated with a decreased likelihood of being in a restriction fragment length polymorphism cluster.

Conclusions  Despite the use of DOTS, patients with drug-resistant TB had a dramatically increased probability of treatment failure and death. Although multi–drug-resistant TB may have a decreased propensity to spread and cause disease, it has a profoundly negative impact on TB control.

From the Instituto Nacional de Salud Pública, Cuernavaca, Mexico (Drs García-García, M. Jiménez-Corona, A. Jiménez-Corona, Palacios-Martínez, Ferreyra-Reyes, and Valdespino-Gómez and Mr Juárez-Sandino); Stanford University, Stanford, Calif (Dr Small); Instituto Nacional de la Nutrición Salvador Zubirán, (Drs Ponce-de-León and Sifuentes-Osornio), and Instituto Nacional de Diagnóstico y Referencia Epidemiológicos (Ms Balanrano-Campos and Mr Olivera-Díaz), Mexico City, Mexico.

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