Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis.

BACKGROUND: Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings. METHODS: Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001. RESULTS: Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions. CONCLUSIONS: In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.

Treatment outcomes of patients with HIV and tuberculosis.

RATIONALE: The optimal length of tuberculosis treatment in patients coinfected with HIV is unknown. OBJECTIVES: To evaluate treatment outcomes for HIV-infected patients stratified by duration of rifamycin-based tuberculosis therapy. METHODS: We retrospectively reviewed data on all patients with tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990 through 2001. Patients were followed for up to 12 months after treatment completion. MEASUREMENTS AND MAIN RESULTS: Of 700 patients, 264 (38%) were HIV infected, 315 (45%) were not infected, and 121 (17%) were not tested. Mean duration of treatment was extended to 10.2 months for HIV-infected patients versus 8.4 months for uninfected/unknown patients (p < 0.001). Seventeen percent of the HIV-infected and 37% of the HIV uninfected/unknown patients received 6 months of rifamycin-based therapy. The relapse rate among HIV-infected was 9.3 per 100 person-years versus 1.0 in HIV-uninfected/unknown patients (p < 0.001). HIV-infected individuals who received a standard 6-month rifamycin-based regimen were more likely to relapse than those treated longer (adjusted hazard ratio, 4.33; p = 0.02). HIV-infected individuals who received intermittent therapy were also more likely to relapse than those treated on daily basis (adjusted hazard ratio, 4.12; p = 0.04). The use of highly active antiretroviral therapy was associated with more rapid conversion of smears and cultures and with improved survival. CONCLUSIONS: HIV-infected patients who received a 6-month rifamycin-based course of tuberculosis treatment or who received intermittent therapy had a higher relapse rate than HIV-infected subjects who received longer therapy or daily therapy, respectively. Standard 6-month therapy may be insufficient to prevent relapse in patients with HIV.

Tuberculosis in healthcare workers: a molecular epidemiologic study in San Francisco.

OBJECTIVE: Healthcare workers (HCWs) are at risk of becoming infected with Mycobacterium tuberculosis through occupational exposure. To identify HCWs who became infected and developed tuberculosis as a result of their work, we studied the molecular epidemiology of tuberculosis in HCWs. DESIGN: Eleven-year prospective cohort molecular epidemiology study. SETTING: City and County of San Francisco, California. PATIENTS: All persons reported with tuberculosis between 1993 and 2003. HCWs were identified from the San Francisco Tuberculosis Control Section's database, and mycobacterial isolates from culture-positive subjects were analyzed by IS6110-based genotyping. RESULTS: Of 2510 cases of tuberculosis reported during the study period, 31 (1.2%) occurred in HCWs: the median age of the HCWs was 37 years, and 11 (35%) were male. HCWs were more likely than non-HCWs to be younger (P=.0036), born in the United States (P=.0004), and female (P=.0003) and to not be homeless (P=.010). The rate of tuberculosis among HCWs remained constant during the study period, despite a significant decrease in the overall case rate in San Francisco. Work-related transmission was documented in at least 10 (32%) of 31 HCWs, including 4 of 8 HCWs whose isolates were part of genotypically determined clusters. Only 1 of 7 cases of tuberculosis in HCWs after 1999 was documented as being work-related. CONCLUSIONS: Although most cases of tuberculosis in HCWs, as in non-HCWs, developed as a result of endogenous reactivation of latent infection, at least half of clustered cases of tuberculosis in HCWs were related to work. The number of work-related cases of tuberculosis in HCWs decreased during the study period.