Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin

N Engl J Med. 1993 Feb 25;328(8):527-32. doi: 10.1056/NEJM199302253280802.


Background and methods: The frequency of infection with multidrug-resistant Mycobacterium tuberculosis is increasing. We reviewed the clinical courses of 171 patients with pulmonary disease due to M. tuberculosis resistant to rifampin and isoniazid who were referred to our hospital between 1973 and 1983. The patients' records were analyzed retrospectively. Their regimens were selected individually and preferably included three medications that they had not been given previously and to which the strain was fully susceptible.

Results: The 171 patients (median age, 46 years) had previously received a median of six drugs and shed bacilli that were resistant to a median of six drugs. Thus, their regimens were frequently not optimal. Of 134 patients with sufficient follow-up data, 87 (65 percent) responded to chemotherapy (as indicated by negative sputum cultures for at least three consecutive months); 47 patients (35 percent) had no response, as shown by continually positive cultures. The median stay in the hospital was more than seven months. In a multivariate analysis, an unfavorable response was significantly associated with a greater number of drugs received before the current course of therapy (odds ratio, 4.0; 95 percent confidence interval, 1.6 to 9.9; P < 0.001) and with male sex (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 6.2; P < 0.03). Twelve of the patients with responses subsequently had relapses. The overall response rate was 56 percent over a mean period of 51 months. Of the 171 patients, 63 (37 percent) died, and 37 of these deaths were attributed to tuberculosis.

Conclusions: For patients with pulmonary tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. Only about half of such patients eventually have negative sputum cultures despite carefully selected regimens administered for extended periods. Failure to control this resistant infection is associated with high mortality and ominous implications for the public health.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / therapeutic use*
  • Drug Resistance, Microbial
  • Female
  • Humans
  • Isoniazid / pharmacology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycobacterium tuberculosis / drug effects
  • Recurrence
  • Retrospective Studies
  • Rifampin / pharmacology
  • Sputum / microbiology
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / mortality


  • Antitubercular Agents
  • Isoniazid
  • Rifampin