Time to sputum conversion in patients with pulmonary tuberculosis: A score to estimate the infectious period.

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period. Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model. Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02-3.41), smoking (2.44, 95% CI:1.36-4.37), >2 affected lung lobes (1.95, 95% CI:1.08-3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24-3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64-0.78). Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period.

Consensus management recommendations for less common non-tuberculous mycobacterial pulmonary diseases.

The 2020 clinical practice guideline for the treatment of non-tuberculous mycobacterial pulmonary disease (NTM-PD) by the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America; and the 2017 management guideline by the British Thoracic Society covered pulmonary diseases in adults caused by Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium abscessus. In order to provide evidence-based recommendations for the treatment of less common non-tuberculous mycobacterial (NTM) species in adult patients without cystic fibrosis or HIV infection, our expert panel group performed systematic literature searches to provide management guidance for pulmonary diseases caused by seven additional organisms: Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium genavense, Mycobacterium gordonae, Mycobacterium malmoense, Mycobacterium simiae, and Mycobacterium szulgai. Treatment recommendations were developed by a structured consensus process. The evidence from the scientific literature published in English for treatment recommendations for pulmonary diseases caused by other NTM species was of very low quality, with the exception of M malmoense, and based on the evaluation of case reports and case series. For M malmoense, results from two randomised controlled trials and three retrospective cohort studies provided a better evidence base for treatment recommendations, although the evidence was still of low quality.

Management of Tuberculosis: Are the Practices Homogeneous in High-Income Countries?

Objectives: To evaluate and compare practices regarding the diagnosis, isolation measures, and treatment of tuberculosis (TB) in high-income countries and mainly in Europe. Materials and Methods: A survey was conducted from November 2018 to April 2019 within the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). The practices observed were compared to the main international guidelines. Results: Among 136 ESGMYC members, 64 (17 countries) responded to the questionnaire. In their practice, two (20.7%) or three sputum samples (79.3%) were collected for the diagnosis of pulmonary TB, alternatively induced sputum (n = 37, 67.2%), bronchoscopy (34, 58.6%), and gastric aspirates (15, 25.9%). Nucleic acid amplification tests (NAATs) were performed by 41 (64%) respondents whatever the smear result and by 47 (73%) in case of smear-positive specimens. NAAT and adenosine deaminase measurement were used for extrapulmonary TB diagnosis in 83.6 and 40.4% of cases, respectively. For isolation duration, 21 respondents (42.9%) were keeping isolation until smear negativity. An initial treatment without ethambutol was offered by 14% (n = 9) of respondents. Corticosteroid therapy, cerebrospinal fluid opening pressure testing, and repeated lumbar puncture were carried out for central nervous system TB by 79.6, 51.9, and 46.3% of the respondents, respectively. For patients with human immunodeficiency virus-TB coinfection, the preferred antiretroviral therapy included dolutegravir 50 mg twice a day (56.8%). Comparing with the recommendations of the main guidelines, the practices are not totally consistent. Conclusion: This study shows heterogeneous practices, particularly for diagnosis, and isolation, although rapid molecular testing is implemented in most centers. More standardization might be needed.

Tumor necrosis factor antagonists for paradoxical inflammatory reactions in the central nervous system tuberculosis: Case report and review.

RATIONALE: Paradoxical reaction/immune reconstitution inflammatory syndrome is common in patients with central nervous system tuberculosis. Management relies on high-dose corticosteroids and surgery when feasible. PATIENT CONCERN: We describe 2 cases of HIV-negative patients with corticosteroid-refractory paradoxical reactions of central nervous system tuberculosis. DIAGNOSES: The 2 patients experienced clinical impairment shortly after starting therapy for TB, and magnetic resonance imaging showed the presence of tuberculomas, leading to the diagnosis of a paradoxical reaction. INTERVENTIONS: We added infliximab, an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, to the dexamethasone. OUTCOMES: Both patients had favorable outcomes, 1 achieving full recovery but 1 suffering neurologic sequelae. LESSONS: Clinicians should be aware of the risk of paradoxical reactions/immune reconstitution inflammatory syndrome when treating patients with tuberculosis of the central nervous system and should consider the prompt anti-TNF-α agents in cases not responding to corticosteroids.

Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.

Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection. / Sumario ejecutivo de la guía de práctica clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa.

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health.

Prevention and Management of Tuberculosis in Transplant Recipients: From Guidelines to Clinical Practice.

Transplant recipients are at increased risk for tuberculosis (TB), which can adversely affect graft viability and patient survival. Scientific societies and official organizations have therefore issued guidelines and consensus statements for TB prevention and treatment. However, due to the poor supporting evidence, the current recommendations largely rely on expert opinion rather than on properly designed studies. In this overview, we aim to gather together the previous experience and compare and contrast the main current guidelines on the prevention and treatment of TB in solid organ transplantation and hematopoietic stem cell transplantation.

Prevention of anti-tumor necrosis factor-associated tuberculosis: a 10-year longitudinal cohort study.

BACKGROUND: The extent to which anti-tumor necrosis factor (TNF)-associated tuberculosis can be prevented is unclear, and there is no established guidance on the optimal screening strategy for latent tuberculosis (LTBI) in patients about to start anti-TNF therapy. We aimed to determine the effectiveness of a comprehensive program for the prevention of anti-TNF-associated tuberculosis, and to evaluate 3 LTBI screening strategies and the need for retesting patients with negative results at baseline. METHODS: In total, 726 patients were screened prior to anti-TNF therapy using 1 of 3 diagnostic strategies over 3 consecutive periods: first, a 2-step tuberculin skin test (TST); second, a 2-step TST plus QuantiFERON-TB Gold In-Tube test (QFT-GIT) (2-step TST/QFT); and third, a single-step TST plus QFT-GIT (TST/QFT). Infected patients were offered preventive therapy. We assessed differences in the incidence of tuberculosis between anti-TNF exposed and nonexposed patients, and between the 3 study periods. RESULTS: Tuberculosis developed during the first year in 2.85 per 1000 exposed patient-years (3/1052 patient-years) and 1.77 per 1000 nonexposed patient-years (1/566 patient-years). No cases occurred beyond the first year of treatment. LTBI diagnoses decreased with the single-step TST/QFT (26.5%) compared with the 2-step TST (42.5%; P < .001) and 2-step TST/QFT (38.5%; P = .02); the incidence of tuberculosis among exposed patients did not change significantly across the 3 periods (2.63/1000, 3.91/1000, and 2.4/1000 patient-years, respectively). CONCLUSIONS: Although anti-TNF-associated tuberculosis can be reduced, some risk remains during the first year of therapy. Neither the 2-step TST nor systematic retesting after negative baseline testing is justified.

Immunodiagnostic Tests' Predictive Values for Progression to Tuberculosis in Transplant Recipients: A Prospective Cohort Study.

BACKGROUND: Little is known about the predictive value for progression to tuberculosis (TB) of interferon-γ release assays and how they compare with the tuberculin skin test (TST) in assessing the risk of TB infection in transplant recipients. METHODS: We screened 50 liver transplant (LT) and 26 hematopoietic stem cell transplant (HSCT) recipients with both QuantiFERON-TB Gold In-tube (QFT-GT) and TST and prospectively followed them for a median of 47 months without preventive chemoprophylaxis. RESULTS: In the LT cohort, 1 in 22 (4.5%) QFT-GT-positive patients developed posttransplant TB, compared with none of the QFT-GT-negative patients. In the HSCT cohort, none of the 7 QFT-GT-positive patients developed TB, whereas 1 case (5.3%) progressed to active TB among the 19 QFT-GT-negative patients. Comparable results were obtained with the TST: in the LT group, 1 of 23 TST-positive and none of the 27 TST-negative patients developed TB; and in the HSCT group, none of the 8 TST-positive and one of the 18 TST-negative patients progressed to active TB. CONCLUSIONS: In this cohort of transplant recipients, the positive predictive value of QFT-GT for progression to active TB was low and comparable to that of TST. Although the risk of developing TB in patients with negative results at baseline is very low, some cases may still occur.

Hyperexcitability of the facial nerve in tuberculous meningitis.

INTRODUCTION: Facial myokymias (FM) are continuous, involuntary, undulating movements of the facial muscles associated with spontaneous electromyographic activity, such as fasciculations and myokymic discharges. They may occur in healthy individuals, or be secondary to multiple sclerosis, posterior fossa tumors, or an inflammatory process. PATIENT AND RESULTS: We describe the case of a 31-year-old man who presented with headache, vomiting, low fever, and disorientation. Cerebrospinal fluid findings included low glucose and high protein content and lymphocyte pleocytosis, with positive culture for Myobacterium tuberculosis. The patient was diagnosed with tuberculous meningitis. Magnetic resonance imaging showed high contrast enhancement in the basal meninges and a left frontal tuberculoma. Over the course of the disease, he experienced FM and persistent, involuntary contraction of the facial muscles. The electromyogram recorded myokymic discharges. DISCUSSION: Tuberculous meningitis is a rare cause of FM. The presence of myokymic discharges on electromyography verified the peripheral origin of facial nerve hyperexcitability in this case, in contrast to persistent contraction of the facial muscles, which has a central origin. The phenomena were transitory and only positive symptoms were observed, with no facial nerve injury. CONCLUSION: Tuberculous meningitis is a rare cause of facial nerve hyperexcitability, which can have a peripheral, nuclear, or supranuclear origin.

Diagnosis of tuberculosis infection by tuberculin skin test and a whole-blood interferon-γ release assay in patients considered for anti-tumor necrosis factor-α therapy.

To assess the performance of QuantiFERON®-TB Gold in-Tube (QFT-GIT; Cellestis, Carnegie, Australia) and tuberculin skin test (TST) in patients with immune-mediated inflammatory diseases (IMID), before anti-tumor necrosis factor-α (TNF-α) therapy, and to compare the results with those from the healthy population. Three hundred fourteen subjects (214 with IMID and 100 controls) underwent simultaneous QFT-GIT and TST. QFT-GIT was positive in 21% of IMID patients and in 16% of controls (P = 0.29). Among IMID patients, 21% tested positive by QFT-GIT and 24%, by TST (P = 0.30). Positive QFT-GIT results were not affected by immunosuppressive therapy (odds ratio, 0.78; 95% confidence interval [CI], 0.36-1.68; P = 0.52). Agreement between both tests in those patients who tested positive by one of the tests was 50% (95% CI, 37.2-62.8). QFT-GIT is useful for identifying IMID patients requiring treatment of latent tuberculosis before anti-TNF therapy. However, given the poor agreement between TST and QFT-GIT, we advocate a strategy of simultaneous testing to optimize diagnostic sensitivity.