Detailed analysis of the radiographic presentation of Mycobacterium kansasii lung disease in patients with HIV infection.

BACKGROUND: Published criteria for the diagnosis of Mycobacterium kansasii lung disease require the presence of clinical symptoms, positive microbiologic results, and radiographic abnormalities. In patients with HIV infection, the radiographic findings of M kansasii lung disease are not well described. METHODS: Medical records and chest radiographs of all patients with HIV infection and at least one respiratory specimen culture positive for M kansasii at San Francisco General Hospital between December 1989 and July 2002 were reviewed. RESULTS: Chest radiographic results were abnormal in 75 of 83 patients (90%) included in the study. Radiographic abnormalities were diverse, with consolidation (66%) and nodules (42%) as the most frequent findings. The mid or lower lung zones were involved in 89% of patients. The pattern of radiographic abnormalities did not differ based on acid-fast bacilli smear status, the presence or absence of coexisting pulmonary infections, or CD4+ T-lymphocyte count. In multivariate Cox regression analysis, cavitation was the only radiographic abnormality independently associated with mortality (hazard ratio, 4.8; 95% confidence interval, 1.2 to 19.6). CONCLUSION: Patients with HIV infection and M kansasii lung disease present with diverse radiographic patterns, most commonly consolidation and nodules predominantly located in the mid and lower lung zones. This finding is in contrast to the upper-lobe cavitary presentation described in patients without HIV infection. Although rare, the presence of cavitary disease in patients with HIV infection and M kansasii independently predicts worse outcome. The diversity in the radiographic presentation of M kansasii lung disease implies that clinicians should obtain sputum mycobacterial culture samples from any patient with HIV infection and an abnormal chest radiograph finding.

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.

Treatment of multidrug-resistant tuberculosis in San Francisco: an outpatient-based approach.

BACKGROUND: Treatment of patients with multidrug-resistant tuberculosis requires prolonged therapy, often involving long hospital stays. Despite intensive and costly therapy, cure rates are relatively low. METHODS: We reviewed the outcomes for all patients with multidrug-resistant tuberculosis treated in San Francisco, California, during 1982-2000 and identified billing charges for patients treated during 1995-2000. Mycobacterium tuberculosis isolates were genotyped by IS6110-based restriction fragment-length polymorphism analysis. RESULTS: Forty-eight cases were identified with resistance to a median of 3 drugs (range, 2-9 drugs). The median age of the patients was 49.5 years (range, 22-78 years); 36 (75%) of 48 patients were foreign born, 11 (23%) were human immunodeficiency virus (HIV) seropositive, and 45 (94%) had pulmonary tuberculosis. Thirty-two (97%) of the 33 HIV-seronegative patients were cured, with only 1 relapse occurring 5 years after treatment. All 11 HIV-seropositive patients died during observation. Twenty-one patients (44%) required hospitalization, with a median duration of stay of 14 days (range, 3-74 days). The estimated inpatient and outpatient aggregate cost for the 11 patients treated after 1994 was $519,928, with a median cost of $27,752 per patient. No secondary cases of multidrug-resistant tuberculosis were identified through population-based genotyping. CONCLUSIONS: Treatment of multidrug-resistant tuberculosis in HIV-seronegative patients largely on an outpatient basis was feasible and was associated with high cure rates and lower cost than in other published studies. Patients with underlying HIV infection had very poor outcomes.

Tuberculosis treatment outcomes: directly observed therapy compared with self-administered therapy.

Effective treatment of tuberculosis requires adherence to a minimum of 6 months treatment with multiple drugs. To improve adherence and cure rates, directly observed therapy is recommended for the treatment of pulmonary tuberculosis. We compared treatment outcomes among all culture-positive patients treated for active pulmonary tuberculosis (n = 372) in San Francisco County, California from 1998 through 2000. Patients treated by directly observed therapy at the start of therapy (n = 149) had a significantly higher cure rate compared with patients treated by self-administered therapy (n = 223) (the sum of bacteriologic cure and completion of treatment, 97.8% versus 88.6%, p < 0.002), and decreased tuberculosis-related mortality (0% vs. 5.5%, p = 0.002). Rates of treatment failure, relapse, and acquired drug resistance were similar between the two groups. Forty-four percent of patients who received self-administered therapy had risk factors for nonadherence and should have been assigned to directly observed therapy. We conclude that treatment plans that emphasize directly observed therapy from the start of therapy have the greatest success in improving tuberculosis treatment outcomes.

Mortality prediction in pulmonary Mycobacterium kansasii infection and human immunodeficiency virus.

In the setting of human immunodeficiency virus (HIV) infection, the clinical implications of American Thoracic Society (ATS) diagnostic criteria and the significance of a single positive respiratory culture for Mycobacterium kansasii are unknown. We retrospectively studied HIV-infected patients with pulmonary M. kansasii isolated between 1989 and 2002 at one institution. Of 127 patients, 33% fulfilled ATS disease criteria. Twenty-nine percent received at least three active drugs for at least 3 months, and 53% died. In survival analysis, a lower CD4 count (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.3) and positive smear microscopy (HR, 2.8; 95% CI, 1.3-6.1) were associated with mortality, whereas antiretroviral therapy (HR, 0.3; 95% CI, 0.1-0.8) and M. kansasii treatment (HR, 0.4; 95% CI, 0.2-0.9) were associated with survival. ATS criteria did not predict mortality (HR, 0.9; 95% CI, 0.4-1.9). Fifteen patients (12%) apparently had indolent infection, not requiring immediate therapy. They had fewer positive cultures and lower rates of positive smear microscopy and ATS-defined disease. In HIV-infected patients with pulmonary M. kansasii infection, predictors of survival include higher CD4 counts, antiretroviral therapy, negative smear microscopy, and adequate treatment for M. kansasii infection, but not ATS diagnostic criteria. Withholding treatment in HIV-infected patients with respiratory M. kansasii isolates should only be considered with negative smear microscopy, few positive cultures, and mild immunosuppression.

A molecular epidemiological assessment of extrapulmonary tuberculosis in San Francisco.

The epidemiology of extrapulmonary tuberculosis (TB) is not well understood. We studied all cases of extrapulmonary TB reported in San Francisco during 1991-2000 to determine risk factors for extrapulmonary TB and the proportion caused by recent infection. Isolates were analyzed by IS6110-based restriction fragment-length polymorphisms analysis. There were 480 cases of extrapulmonary TB, of which 363 (76%) were culture positive; isolates were genotyped for 301 cases (83%). Multivariate analysis identified young age, female sex, and HIV infection as independent risk factors for nonrespiratory TB (excluding pulmonary, pleural, and disseminated TB). Pleural TB was less common in HIV-seropositive persons and women than were nonrespiratory forms of extrapulmonary TB. Pleural TB is different from other forms of extrapulmonary TB and is associated with the highest clustering rate (35% of cases) of all forms of TB. This high rate of clustering occurs because pleural TB is often an early manifestation of recent infection.