Effect of drug resistance on the generation of secondary cases of tuberculosis.
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.
Burgos
Marcos
M
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University Medical Center, Stanford, California, USA. mburgos@salud.unm.edu
DeRiemer
Kathryn
K
Small
Peter M
PM
Hopewell
Philip C
PC
Daley
Charles L
CL
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
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004251:DNA Transposable Elements; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin