Reply to Bttger et al.

    Department of Internal Medicine, Division of Infectious Diseases, University of New Mexico, and Department of Medicine, Veterans Affairs Medical Center, Albuquerque
    Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University Medical Center, Stanford, Bill and Melinda Gates Foundation, Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, and University of California, San Francisco
    Division of Mycobacterial and Respiratory Infections, National Jewish Medical and Research Center, Denver, Colorado

    We appreciate the comments of Bttger et al. [1] concerning our recently published article [2]. In our analysis, we estimated the number of secondary cases that arose from all drug-susceptible and drug-resistant cases by assuming that strains were transmitted to other patients if the drug-susceptibility test results and genotype patterns were identical. We calculated the number of secondary cases for each drug-resistance pattern and determined the secondary-case rate ratio (SR). Bttger et al. questioned the large differences in SRs, especially the increased SR for rifampin-resistant cases. The most likely explanation for the high SR observed among rifampin-resistant cases was the increased incidence of HIV infection among patients with this resistance pattern. We found that the secondary cases caused by rifampin-resistant strains occurred mainly among patients with HIV infection; 77.8% (7/9) of the secondary cases with rifampin resistance occurred in HIV-positive individuals [1]. In addition, almost every case of rifampin-resistant tuberculosis in San Francisco was in an HIV-infected individual. Therefore, it is difficult to draw conclusions about the effect of rifampin resistance on bacterial fitness. The heterogeneity of SR values found among persons with infections resistant to isoniazid and to streptomycin in our study are in agreement with the literature cited by Bttger et al., so it is not clear why the authors are puzzled by these findings. We concur with Bttger et al. that the application of epidemiological methodologies, in conjunction with molecular and genomic tools, is needed to achieve a more refined understanding of the biology of drug-resistant tuberculosis in its natural population.

    References

    1.  Bttger EC, Pletschette M, Anderson D. Drug resistance and fitness in Mycobacterium tuberculosis . J Infect Dis 2005; 191:8234 (in this issue). First citation in article

    2.  Burgos M, DeRiemer K, Small PM, Hopewell PC, Daley CL. Effect of drug resistance on the generation of secondary cases of tuberculosis. J Infect Dis 2003; 188:187885. First citation in article