Performance of Cepheid ® Xpert MTB/RIF ® and TB-Biochip ® MDR in two regions of Russia with a high prevalence of drug-resistant tuberculosis.

The purpose of this study was to assess the performance of Cepheid® Xpert MTB/RIF® ("Xpert") and TB-Biochip® MDR ("TB-Biochip"). Sputum specimens from adults with presumptive tuberculosis (TB) were homogenized and split for: (1) direct Xpert and microscopy, and (2) concentration for Xpert, microscopy, culture [Lowenstein-Jensen (LJ) solid media and Mycobacteria Growth Indicator Tube® (MGIT)], indirect drug susceptibility testing (DST) using the absolute concentration method and MGIT, and TB-Biochip. In total, 109 of 238 (45.8 %) specimens were culture-positive for Mycobacterium tuberculosis complex (MTBC), and, of these, 67 isolates were rifampicin resistant (RIF-R) by phenotypic DST and 64/67 (95.5 %) were isoniazid resistant (INH-R). Compared to culture of the same specimen, a single direct Xpert was more sensitive for detecting MTBC [95.3 %, 95 % confidence interval (CI), 90.0-98.3 %] than direct (59.6 %, 95 % CI, 50.2-68.5 %) or concentrated smear (85.3 %, 95 % CI, 77.7-91.1 %) or LJ culture (80.8 %, 95 % CI, 72.4-87.5 %); the specificity was 86.0 % (95 % CI, 78.9-91.3 %). Compared with MGIT DST, Xpert correctly identified 98.2 % (95 % CI, 91.5-99.9 %) of RIF-R and 95.5 % (95 % CI, 85.8-99.2 %) of RIF-susceptible (RIF-S) specimens. In a subset of 104 specimens, the sensitivity of TB-Biochip for MTBC detection compared to culture was 97.3 % (95 % CI, 91.0-99.5 %); the specificity was 78.1 % (95 % CI, 61.5-89.9 %). TB-Biochip correctly identified 100 % (95 % CI, 94.2-100 %) of RIF-R, 94.7 % (95 % CI, 76.7-99.7 %) of RIF-S, 98.2 % (95 % CI, 91.4-99.9 %) of INH-R, and 78.6 % (95 % CI, 52.1-94.2 %) of INH-S specimens compared to MGIT DST. Xpert and Biochip were similar in accuracy for detecting MTBC and RIF resistance compared to conventional culture methods.

Quantification of multidrug-resistant M. tuberculosis bacilli in sputum during the first 8 weeks of treatment.

SETTING: Mulago Hospital, Kampala, Uganda.OBJECTIVE: To quantify Mycobacterium tuberculosis in sputum during the first 8 weeks of pulmonary multidrug-resistant TB (MDR-TB) treatment.DESIGN: We enrolled consecutive adults with pulmonary MDR-TB treated according to national guidelines. We collected overnight sputum samples before treatment and weekly. Sputum samples were cultured on Middlebrook 7H11S agar to measure colony-forming units per mL (cfu/mL) and in MGIT™ 960™ media to measure time to detection (TTD). Linear mixed-effects regression was used to estimate the relational change in log10 cfu/mL and TTD.RESULTS: Twelve adults (median age: 27 years) were enrolled. Half were women, and two-thirds were HIV-positive. At baseline, median log10 cfu/mL was 5.1, decreasing by 0.29 log10 cfu/mL/week. The median TTD was 116.5 h, increasing in TTD by 36.97 h/week. The weekly change was greater in the first 2 weeks (-1.04 log10 cfu/mL/week and 120.02 h/week) than in the remaining 6 weeks (-0.17 log10 cfu/mL/week and 26.11 h/week).CONCLUSION: Serial quantitative culture measures indicate a slow, uneven rate of decline in sputum M. tuberculosis over 8 weeks of standardized pulmonary MDR-TB treatment.

What will it take to eliminate drug-resistant tuberculosis?

Drug-resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but this situation is slowly changing. If the world is to drastically reduce the incidence of DR-TB, we must stop creating new DR-TB as an essential first step. The DR-TB epidemic that is ongoing should also be directly addressed. First-line drug resistance must be rapidly detected using universal molecular testing for resistance to at least rifampin and, preferably, other key drugs at initial TB diagnosis. DR-TB treatment outcomes must also improve dramatically. Effective use of currently available, new, and repurposed drugs, combined with patient-centered treatment that aids adherence and reduces catastrophic costs, are essential. Innovations within sight, such as short, highly effective, broadly indicated regimens, paired with point-of-care drug susceptibility testing, could accelerate progress in treatment outcomes. Preventing or containing resistance to second-line and novel drugs is also critical and will require high-quality systems for diagnosis, regimen selection, and treatment monitoring. Finally, earlier detection and/or prevention of DR-TB is necessary, with particular attention to airborne infection control, case finding, and preventive therapy for contacts of patients with DR-TB. Implementing these strategies can overcome the barrier that DR-TB represents for global TB elimination efforts, and could ultimately make global elimination of DR-TB (fewer than one annual case per million population worldwide) attainable. There is a strong cost-effectiveness case to support pursuing DR-TB elimination; however, achieving this goal will require substantial global investment plus political and societal commitment at national and local levels.

Loss to follow-up among patients receiving anti-tuberculosis treatment, Haiti, 2011-2015.

Setting: Tuberculosis (TB) treatment facilities in Haiti. Objective: To assess factors associated with loss to follow-up (LTFU) among patients receiving treatment for tuberculosis (TB) in Haiti. Design: We analyzed Haiti's national surveillance data for patients started on anti-tuberculosis treatment from 2011 to 2015 to determine factors associated with LTFU using multivariable logistic regression and describe LTFU in terms of subnational units to target future intervention strategies. We also conducted a survival analysis to estimate hazard ratios of factors associated with time to LTFU. Results: Of 81 490 TB cases reported, 7423 (9.1%) were LTFU during anti-tuberculosis treatment, increasing from 7.1% in 2011 to 10.3% in 2015. Six high-volume facilities had significantly higher rates of LTFU (14.3-31.9%) than the rest of the country, accounting for 18.8% of all TB cases reported, but 41.7% of all LTFU patients. Male sex, previous treatment history, and human immunodeficiency virus infection were associated with higher rates of LTFU. The median time to LTFU was 94 days. Conclusion: A small number of facilities accounted for disproportionately high rates of LTFU. These results identify characteristics of facilities and individuals leading to concentrated interventions to reduce LTFU and improve treatment success.

Contexte : Structures de traitement de la tuberculose (TB) en Haïti.Objectif : Evaluer les facteurs associés à la perte de vue (LTFU) parmi les patients recevant un traitement de TB en Haïti.Schéma : Nous avons analysé les données de surveillance nationale de Haïti pour les patients mis sous traitement de TB entre 2011 et 2015, afin de déterminer les facteurs associés aux LTFU grâce à une régression logistique multivariée, et nous avons décrit les LTFU par unités sous-nationales afin de cibler les stratégies d'intervention futures. Nous avons également réalisé une analyse de survie afin d'estimer les ratios de risque des facteurs associés au délai de LTFU.Résultats : Sur 81 490 cas de TB rapportés, 7423 (9,1%) ont été perdus de vue pendant le traitement de TB, augmentant de 7,1% en 2011 à 10,3% en 2015. Six structures à haut débit de patients ont eu des taux de LFTU significativement plus élevés (14,3­31,9%) que le reste du pays, représentant 18,8% de tous les cas de TB rapportés, mais 41,7% de tous les patients perdus de vue. Le sexe masculin, des antécédents de traitement préalable, et une infection au virus de l'immunodéficience humaine ont été associés à des taux plus élevés de LTFU. Le délai médian de LTFU a été de 94 jours.Conclusion : Un petit nombre de structures ont des taux disproportionnellement élevés de LTFU. Ces résultats identifient les caractéristiques des structures et des individus aboutissant à des interventions ciblées afin de réduire les LTFU et d'améliorer le taux de succès du traitement.

Marco de referencia: Establecimientos de tratamiento de la tuberculosis (TB) en Haití.Objetivo: Evaluar los factores que se asocian con la pérdida durante el seguimiento (LTFU) de los pacientes que reciben tratamiento antituberculoso en Haití.Método: Se analizaron los datos nacionales de vigilancia de los pacientes que iniciaron tratamiento antituberculoso del 2011 al 2015 en Haití, con el objeto de determinar los factores asociados con la LTFU mediante modelos de regresión logística multivariante y se describieron estas pérdidas por unidades subnacionales, con el fin de orientar las futuras estrategias de intervención. Se practicó además un análisis de supervivencia con el fin de estimar los cocientes de riesgos instantáneos de los factores asociados con el tiempo transcurrido hasta la LTFU.Resultados: De los 81 490 casos de TB notificados, se perdieron durante el seguimiento del tratamiento antituberculoso 7423 (9,1%) y se observó un aumento del 7,1% en el 2011 al 10,3% en el 2015. En seis establecimientos con alta carga asistencial se encontraron tasas significativamente más altas de LTFU (14,3­31,9%) que en el resto del país y correspondieron al 18,8% de todos los casos de TB notificados, pero al 41,7% de todos los pacientes pérdidas. Los factores que se asociaron con tasas más altas de LTFU fueron el sexo masculino, el antecedente de tratamiento y la infección por el virus de la inmunodeficiencia humana. La mediana del lapso transcurrido hasta la LTFU fue 94 días.Conclusión: Un número pequeño de establecimientos contribuyó con tasas desproporcionadamente altas de LTFU. Estos resultados ponen de manifiesto las características de las instalaciones y de las personas que deben orientar las intervenciones dirigidas, encaminadas a disminuir la LTFU y mejorar el éxito terapéutico.

Low body mass index and latent tuberculous infection: a systematic review and meta-analysis.

BACKGROUND: The well-documented association between underweight and increased incidence of active tuberculosis (TB) has not been extended to incidence or prevalence of latent tuberculous infection (LTBI). DESIGN: After identifying studies that reported a categorical measure of body mass index (BMI) and used the tuberculin skin test (TST) or QuantiFERON®-TB Gold In-Tube (QFT) to measure LTBI, a maximum likelihood random-effects model was used to examine the pooled association between LTBI and low BMI (<18.5 kg/m2), compared with 1) normal BMI (18.5-25 kg/m2) and 2) a complementary group of all others, i.e., non-underweight subjects (BMI 18.5 kg/m2). RESULTS: Among studies using TST, the odds ratios (ORs) showed a slight, non-statistically significant decrease in the odds of TST positivity in underweight persons compared with both groups (non-underweight, OR 0.88, 95%CI 0.73-1.05; normal weight, OR 0.96, 95%CI 0.77-1.20). Among studies using QFT, the OR suggested slightly decreased, yet non-significant, odds of QFT positivity in underweight compared with non-underweight subjects (OR 0.92, 95%CI 0.68-1.26), and significantly decreased odds of QFT positivity in underweight compared with normal weight subjects (OR 0.84, 95%CI 0.73-0.98). CONCLUSION: These results suggest that underweight persons are not at an increased risk of LTBI. Screening this population for LTBI would not increase the yield of identified LTBI.

Population-based risk factors for tuberculosis and adverse outcomes among Tibetan refugees in India, 1994-1996.

SETTING: Tibetan refugees in India, 1994-1996. OBJECTIVE: To determine tuberculosis (TB) incidence, independent risk factors for TB, and predictors of adverse outcomes. DESIGN: Data from a house-to-house census/demographic survey were merged with TB patient data. Separate multivariable models for each birthplace were developed for outcomes of interest. RESULTS: From 1994 to 1996, 47,491 Tibetans were surveyed and 1197 TB cases confirmed (incidence 835/ 100,000). Risk factors for TB in separate multivariable models differed by place of birth. Independent predictors of death for Tibet-born refugees included age >50 years, extra-pulmonary TB, and second-line therapy, while for India-born refugees they included second-line therapy and no improvement at the end of treatment. No significant risk factors for default were identified for Tibet-born refugees, while region of residence and the absence of a BCG scar were independent predictors among those born in India. Predictors of receipt of second-line therapy among Tibet-born refugees included region, years in camps, and prior TB, while among those born in India they were region, age > or =20 years, sputum-positive at diagnosis, and previous TB. CONCLUSIONS: TB incidence in Tibetan refugee settlements exceeds the highest national TB rates, and country of birth determines risk factors. TB control efforts in India should include this population.

Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis.

SETTING: Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist. OBJECTIVE: To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy. DESIGN: Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement. RESULTS: Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs. CONCLUSION: Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.

Capacity building for international tuberculosis control through operations research training.

SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the national, provincial, and even district levels have the basic analytical and epidemiological skills necessary for collecting and analyzing quality data pertaining to national TB control program (NTP) improvements. This includes setting program priorities, operations planning, and implementing and evaluating program activities. OBJECTIVES: To present a model course for building capacity in basic epidemiology and operations research (OR). DESIGN: A combination of didactic lectures and applied field exercises were used to achieve the main objectives of the 6-day OR course. These were to increase the understanding of quantitative and qualitative research concepts, study design, and analytic methods, and to increase awareness of how these methods apply to the epidemiology and control of TB; and to demonstrate the potential uses of OR in answering practical questions on NTP effectiveness. As a final outcome, course participants develop OR proposals that are funded and later implemented. RESULTS: Since 1997, this OR course has been conducted nine times in five countries; 149 key NTP and laboratory staff have been trained in OR methods, and 44 OR protocols have been completed or are underway. CONCLUSION: This low-cost model course can be adapted to a wide range of public health issues.

Annual risk of tuberculous infection measured using serial skin testing, Orel Oblast, Russia, 1991-2005.

OBJECTIVE: To compare trends in direct annual risk of tuberculous infection (ARTI) during 1991-2005 in relation to tuberculosis (TB) incidence and to indirect estimates of ARTI derived from the prevalence of tuberculin skin test (TST) positivity in schoolchildren in Orel Oblast, Russia. DESIGN: In 2005, we abstracted annual TST results and vaccination histories from a representative sample of schoolchildren in Orel Oblast, Russia, where bacille Calmette-Guerin (BCG) vaccination and annual TST of children are nearly universal. We calculated direct ARTI based on the percentage of children tested with TST conversions each year, excluding conversions following BCG vaccination. RESULTS: We analysed records from 13 206 children, with a median of 10 recorded TST results per child. The ARTI increased from 0.2% in 1991 to 1.6% in 2000, paralleling trends in TB incidence. Similar results were observed when the ARTI was estimated based on prevalence of infection among children aged 3-5 years using a 12 mm cut-off to define TST positivity. Results differed substantially when 10 or 15 mm cut-offs were used or when prevalence was determined among children aged 6-8 years. CONCLUSION: ARTI measured through TST conversion increased as TB incidence increased in Orel Oblast. ARTI measured through serial TSTs can thus provide an indicator of changing trends in TB incidence.

Intestinal parasites and HIV infection in Tanzanian children with chronic diarrhea.

OBJECTIVE: To determine whether specific intestinal parasites are associated with HIV infection in Tanzanian children with chronic diarrhea. DESIGN: A prospective, cross-sectional study. SETTING: Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. SUBJECTS: All children aged 15 months to 5 years admitted with chronic diarrhea, and age-matched controls. METHODS: Standardized history, physical examination, HIV serology, and stool parasitology were evaluated for all subjects. We compared three groups: HIV-infected and non-HIV-infected children with chronic diarrhea and controls without diarrhea. MAIN OUTCOME MEASURES: Fecal parasites and nutritional status. RESULTS: Chronic diarrhea accounted for one-quarter of all cases of diarrheal disease in the defined age range, and children with chronic diarrhea were severely malnourished. Forty per cent of subjects with chronic diarrhea were HIV-seropositive. Although intestinal parasites were detected in approximately 50% of all three groups, diarrheagenic parasites were detected in up to 40% of children with chronic diarrhea. Blastocystis hominis was detected only in HIV-infected patients. CONCLUSIONS: HIV infection was common in children with chronic diarrhea, and parasitic agents of diarrhea may be important in children with chronic diarrhea both with and without HIV infection in this setting. B. hominis was more frequent in HIV-infected children. The immunocompromising effects of severe malnutrition may have diminished the difference between HIV-infected and non-HIV-infected children.

PIP: The authors attempted to determine whether specific intestinal parasites are associated with HIV infection in Tanzanian children with chronic diarrhea. This prospective, cross-sectional study included all children aged 15 months to 5 years admitted with chronic diarrhea and a group of age-matched controls and took place at Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. Standardized history, physical examination, HIV serology, and stool parasitology were evaluated for all subjects. The authors compared 3 groups - HIV infected and non-HIV-infected children with chronic diarrhea and controls without diarrhea--and they measured fecal parasites and nutritional status. Chronic diarrhea accounted for one-fourth of all cases of diarrheal disease in the defined age range, and children with chronic diarrhea were severely malnourished. 40% of all subjects with chronic diarrhea were HIV-seropositive. Although intestinal parasites were detected in approximately 50% of all 3 groups, diarrheagenic parasites were detected in up to 40% of children with chronic diarrhea. Blastocystis hominis was detected only in HIV-infected patients. HIV infection was common in children with chronic diarrhea, and parasitic agents of diarrhea may be important in children with chronic diarrhea both with and without HIV infection in this setting. B. hominis was more frequent in HIV-infected children. The immunocompromising effects of severe malnutrition may have diminished the differences between HIV-infected and non-HIV-infected children.

Gender differences in early suspicion of tuberculosis in hospitalized, high-risk patients during 4 epidemic years, 1987 to 1990.

OBJECTIVES: To assess the degree to which, from 1987 to 1990, physicians suspected tuberculosis (TB) in the first 2 hospital days in human immunodeficiency virus (HIV)-infected patients with pulmonary disease. DESIGN: Retrospective cohort study. SETTING: 96 hospitals in five US cities. PATIENTS: 2,174 adult patients with acquired immunodeficiency syndrome discharged with a diagnosis of Pneumocystis carinii pneumonia from 1987 to 1990. The diagnosis generally was not known on admission. RESULTS: Physicians suspected TB in the first 2 hospital days in 66% of these patients in 1987, a rate that increased steadily to 74% in 1990. However, the extent to which physicians considered TB among female patients decreased from 76% to 71% over the 4 years. Controlling for confounding variables by multiple logistic regression, the odds that TB would be suspected early increased 1.8-fold among men (odds ratio [OR], 1.8; 95% confidence interval [CI95], 1.4-2.4), but not in women (OR, 0.6; CI95, 0.2-1.9). Among the five cities, the odds of early suspicion of TB increased most in New York City (OR, 3.9; CI95, 2.0-7.9). CONCLUSIONS: Physicians considered TB in a timely manner in an increasing majority of male, but not female, high-risk patients during the first years of TB resurgence in the United States. Physicians must be aware of the changing epidemiology of HIV and TB, as well as their practice patterns, to prevent nosocomial transmission of this disease.

The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals.

The oral traditions of medicine and public health have it that malnutrition is an important risk factor for the development of tuberculosis (TB). Malnutrition profoundly affects cell-mediated immunity (CMI), and CMI is the principle host defense against TB. It makes biological sense. Although most health professionals readily accept this principle, much of this belief is based on uncontrolled observations such as disaster situations or on backwards logic from the cachexia common among TB patients. In fact, the evidence in humans is surprisingly thin from the perspective of scientific rigor. And few data, if any, quantify the extent of the relative or attributable risk of TB due to malnutrition. Moreover, until recently, data from experimental animals were based on animal models that were largely not relevant to human TB infection and disease. This article reviews the scientific data supporting the contention that malnutrition is an important risk factor for TB concentrating on observations in humans and on experimental animal studies based on a highly relevant animal model. If it is true, malnutrition may account for a greater population attributable risk of TB than HIV infection, and certainly a much more correctable one.

Rurality and tuberculosis incidence trends in North and South Carolina, 1980 to 1992.

U.S. tuberculosis incidence rates increased steadily from 1985 through the end of 1992. Many factors have been implicated as contributors to the reversal in the historic decline of tuberculosis: the HIV epidemic, poverty and homelessness, immigration from less developed countries, and a deteriorating public health infrastructure. The purposes of this study were to demonstrate the extent of geographic variation in tuberculosis incidence rate trends in North and South Carolina and to quantify the association between aggregate-level characteristics of state economic areas and incidence rate trends. Data were obtained from the U.S. 1980 and 1990 decennial census and from the North and South Carolina health departments. In North Carolina, tuberculosis trends declined rapidly in the early 1980s, but declined much less rapidly from 1986 to 1992. In South Carolina, tuberculosis trends were nearly static during the early 1980s, but declined rapidly from 1986 to 1992. Rural and high-poverty state economic areas in South Carolina experienced especially favorable changes in tuberculosis incidence trends. South Carolina has a unique tuberculosis control program that makes widespread use of enablers, incentives, and directly observed therapy. This study demonstrates the distinct tuberculosis incidence trends that existed in two contiguous states and suggests that approaches to tuberculosis control that improve access to care may be effective in improving tuberculosis incidence trends, particularly in poor and rural areas. Strengthening tuberculosis programs may be an important strategy for controlling the current resurgence of tuberculosis in the United States.

A tuberculosis hotline in Tyler: a Texas resource for primary health care providers for the control of infectious diseases.

The Center for Pulmonary and Infectious Disease Control (CPIDC), located on the campus of The University of Texas Health Center in Tyler, manages a toll-free infectious disease consultation hotline advertised to public and private physicians and to health care agencies throughout the state. From January 1994 through December 1996, as part of a statewide initiative to curb an unprecedented increase in the incidence of tuberculosis observed since 1985, a concentrated effort was made to solicit health care providers for consultation requests that involved the diagnosis and management of tuberculosis, in particular, drug-resistant varieties. During that period, 3447 calls were made to the CPIDC by 1682 physicians and nurses. While most of the calls originated from 4 major urban areas plus health care facilities along the border, calls were received from more than half of all the counties in Texas. The value of providing an infectious disease consultation service, readily available, without charge, to all members of the health care community is discussed.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.

Impact of second-line drug resistance on tuberculosis treatment outcomes in the United States: MDR-TB is bad enough.

SETTING: The worldwide emergence of extensively drug-resistant tuberculosis (TB) has focused attention on treatment with second-line drugs (SLDs). OBJECTIVE: To determine the impact on outcomes of resistance to individual SLDs, we analyzed successful treatment completion and death among drug-resistant TB cases in the US national TB surveillance system, 1993-2007 (N = 195 518). DESIGN: We defined four combinations of first-line drug (FLD) resistance based on isoniazid (INH) and rifamycin, and three patterns of SLD resistance: fluoroquinolones, injectable SLDs and other oral SLDs. We compared treatment outcomes of cases by FLD resistance, with and without each pattern of SLD resistance. RESULTS: In all but one instance, cases with FLD resistance but no SLD resistance had better outcomes than cases with SLD resistance. Rifamycin resistance, alone or with INH, resulted in a greater decline in treatment completion and greater increase in deaths than resistance to SLDs. Among patients with multidrug-resistant TB, additional resistance to injectable SLDs was statistically significant. Outcomes were better for human immunodeficiency virus (HIV) negative than HIV-positive cases for all resistance patterns, but improved among HIV-infected cases after 1998, when highly active antiretroviral treatment became widely available. CONCLUSION: These results suggest that the effect of rifamycin resistance may outweigh the more modest effects of resistance to specific SLDs.