title: Effect of drug resistance on the generation of secondary cases of tuberculosis.
abstract: BACKGROUND
  The results of animal studies suggest that isoniazid-resistant strains of Mycobacterium tuberculosis are less pathogenic than isoniazid-susceptible strains. Here, we assess the relative pathogenicity of drug-resistant and drug-susceptible strains, in a human population.
  
  
  METHODS
  We linked IS6110 genotype patterns of M. tuberculosis strains with drug-susceptibility test results and epidemiologic information for 85% of culture-positive incident cases of tuberculosis (TB) in San Francisco during 1991-1999. We assumed that drug-susceptible and drug-resistant strains were transmitted to secondary case patients if the drug-resistance and genotype patterns were identical. We calculated the number of secondary cases for each drug-resistance pattern and determined the relative secondary-case rate ratio (SR) of drug-resistant TB to drug-susceptible TB.
  
  
  RESULTS
  There were 1800 patients with culture-positive TB, drug-susceptibility test results, and genotyping results. The overall SR of drug-resistant to drug-susceptible TB cases was 0.51 (95% confidence interval [CI], 0.37-0.69). The SR was 0.29 (95% CI, 0.15-0.57) for isoniazid-resistant strains, 0.10 (95% CI, 0.02-0.42) for strains resistant to both isoniazid and streptomycin, and 0.88 (95% CI, 0.53-1.47) for streptomycin-resistant strains. There were no secondary cases caused by multidrug-resistant (MDR) TB. The SR for rifampin-resistant cases was 2.33 (95% CI, 1.04-5.25). Seventy-eight percent (7/9) of the patients with rifampin-resistant secondary cases of TB were seropositive for human immunodeficiency virus.
  
  
  CONCLUSIONS
  In the context of an effective TB program in San Francisco, strains that were resistant to isoniazid either alone or in combination with other drugs were less likely to result in secondary cases than were drug-susceptible strains. In this setting, isoniazid-resistant and MDR TB cases were not likely to produce new, incident drug-resistant TB cases.
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University Medical Center, Stanford, California, USA. mburgos@salud.unm.edu
authors.forename: Marcos
authors.initials: M
authors.lastname: Burgos
authors.forename: Kathryn
authors.initials: K
authors.lastname: DeRiemer
authors.forename: Peter M
authors.initials: PM
authors.lastname: Small
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hopewell
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D016001:Confidence Intervals; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology; D012495:San Francisco / Q000453:epidemiology; D013307:Streptomycin / Q000494:pharmacology; D014376:Tuberculosis / Q000453:epidemiology* / Q000635:transmission
chemical_list: D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004251:DNA Transposable Elements; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin