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1.
Arch Bronconeumol ; 2020 May 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32446667

RESUMO

New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects.

2.
Arch Bronconeumol ; 2019 Nov 23.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31771919

RESUMO

BACKGROUND: Tuberculosis (TB) represents a diagnostic and therapeutic challenge for solid organ transplant recipients, particularly after lung transplant (LT). Our aim was to determine the impact of TB in LT patients in Spain, considering prevalence, clinical presentation, prevention and therapeutic management. In addition, differences in outcome between rifampicin (RIF) versus non-RIF containing regimens were analyzed. METHODS: Multicenter, observational retrospective study, including all cases of TB diagnosed in recipients after LT, in five pulmonary transplant units in Spain, between January 1990 and December 2017. RESULTS: Among 2962 LT recipients, 45 cases of TB were diagnosed, resulting in a prevalence of 1.52%. Most of them (88.89%) were diagnosed during the first year posttransplantation, 86.67% with pulmonary presentation. Screening for latent TB infection (LTBI) was done in 36 of the 45 patients and LTBI was detected pretransplant in 12 (33.33%). Less than half of the patients with disease (42.22%) received rifampicin (RIF). Lower probability of TB worsening was found in RIF-containing regimens (p=0.049), as well as longer survival (p=0.001). RIF use was not associated with an increased risk in rejection (p=0.99), but doses of calcineurin inhibitors (CNI) had to be raised an average of 215%. CONCLUSIONS: Risk of TB after LT was lower in our series than previously reported. TB should be searched during the first year posttransplant in patients with TB risk factors. Pulmonary presentation was predominant. More sensitive algorithms for detecting LTBI before LT are crucial. It is reasonable to use RIF-containing regimens over non-RIF regimens based on the tendency toward better outcome in our series. RIF regimen requires close monitoring of CNI trough level for 2-3 weeks, until stability is achieved.

3.
Arch Bronconeumol ; 2019 Nov 25.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31780285

RESUMO

OBJECTIVE: The objective of the study was to determine the trend of variables related to tuberculosis (TB) from the Integrated Tuberculosis Research Program (PII-TB) registry of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and to evaluate the PII-TB according to indicators related to its scientific objectives. METHOD: Cross-sectional, population-based, multicenter study of new TB cases prospectively registered in the PII-TB between 2006 and 2016. The time trend of quantitative variables was calculated using a lineal regression model, and qualitative variables using the χy test for lineal trend. RESULTS: A total of 6,892 cases with an annual median of 531 were analyzed. Overall, a significant downward trend was observed in women, immigrants, prisoners, and patients initially treated with 3 drugs. Significant upward trends were observed in patients aged 40-50 and > 50 years, first visit conducted by a specialist, hospitalization, diagnostic delay, disseminated disease and single extrapulmonary location, culture(+), sensitivity testing performed, drug resistance, directly observed treatment, prolonged treatment, and death from another cause. The scientific objectives of the PII-TB that showed a significant upward trend were publications, which reached a maximum of 8 in 2016 with a total impact factor of 49,664, numbers of projects initiated annually, presentations at conferences, and theses. CONCLUSIONS: PII-TB provides relevant information on TB and its associated factors in Spain. A large team of researchers has been created; some scientific aspects of the registry were positive, while others could have been improved.

6.
Int J Infect Dis ; 83: 72-76, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30953827

RESUMO

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.


Assuntos
Antituberculosos/efeitos adversos , Diarilquinolinas/efeitos adversos , Nitroimidazóis/efeitos adversos , Oxazóis/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Diarilquinolinas/administração & dosagem , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Nitroimidazóis/administração & dosagem , Oxazóis/administração & dosagem , Projetos Piloto , Tuberculose/tratamento farmacológico , Organização Mundial da Saúde
8.
Semin Respir Crit Care Med ; 39(3): 310-324, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30071546

RESUMO

Drug-resistant strains of Mycobacterium tuberculosis pose a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment of tuberculosis, as well as unchecked transmission of M. tuberculosis, has resulted in alarming levels of drug-resistant tuberculosis. The World Health Organization (WHO) estimates that there were 600,000 cases of multidrug-resistant tuberculosis (MDR-TB)/rifampin-resistant (RR) tuberculosis in 2016, defined as strains that are resistant to at least isoniazid and rifampicin. Globally, WHO estimates that 4.1% of new tuberculosis cases and 19% of retreatment cases have MDR-TB. By the end of 2016, 123 countries had reported at least one case of extensively drug-resistant strains, which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. It is estimated that only 22% of all MDR-TB cases are currently receiving therapy. This article reviews the management of MDR/RR-TB and updates recommendations regarding the use of shorter course regimens and new drugs.


Assuntos
Antituberculosos/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Saúde Global , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Organização Mundial da Saúde
15.
Arch. bronconeumol. (Ed. impr.) ; 53(9): 501-509, sept. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-166280

RESUMO

En las últimas 2 décadas la tuberculosis con resistencia a fármacos se ha convertido en una amenaza y un reto para la salud pública mundial. El diagnóstico y el tratamiento de estas formas de tuberculosis es mucho más complejo, y el pronóstico empeora claramente a medida que se incrementa el patrón de las resistencias. Sin embargo, es necesario destacar cómo con el manejo clínico y programático adecuado de estos enfermos se puede conseguir la curación de una mayoría de ellos. En esta normativa se razonan las bases del diagnóstico y tratamiento de todos los pacientes afectos de tuberculosis, desde aquellos que tienen formas de la enfermedad con sensibilidad a todos los fármacos hasta aquellos que son portadores de los patrones más extensos de resistencia. Asimismo, se dan recomendaciones específicas para cada uno de estos supuestos. También se aborda el papel que ya están teniendo y pueden tener en un futuro inmediato los nuevos métodos moleculares de detección de resistencias, los esquemas acortados de tratamiento de la tuberculosis multi-farmacorresistente (TB-MDR) y los nuevos fármacos con actividad frente a Mycobacterium tuberculosis (AU)


In the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. The diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. Nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. These guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, from those infected by strains that are sensitive to all drugs, to those who are extensively drug-resistant. Specific recommendations are given forall cases. The current and future role of new molecular methods for detecting resistance, shorter multi-drug-resistant tuberculosis regimens, and new drugs with activity against Mycobacterium tuberculosis are also addressed (AU)


Assuntos
Humanos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Padrões de Prática Médica , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/patogenicidade , Fatores de Risco , Técnicas de Diagnóstico Molecular
17.
Eur Respir J ; 49(5)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28529205

RESUMO

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.


Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Carbapenêmicos/uso terapêutico , Clofazimina/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Humanos , Linezolida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Escarro/metabolismo , Resultado do Tratamento
18.
Arch Bronconeumol ; 53(9): 501-509, 2017 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28359606

RESUMO

In the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. The diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. Nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. These guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, from those infected by strains that are sensitive to all drugs, to those who are extensively drug-resistant. Specific recommendations are given forall cases. The current and future role of new molecular methods for detecting resistance, shorter multi-drug-resistant tuberculosis regimens, and new drugs with activity against Mycobacterium tuberculosis are also addressed.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/classificação , Antituberculosos/farmacologia , Busca de Comunicante , Gerenciamento Clínico , Quimioterapia Combinada , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Técnicas de Genotipagem , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Guias de Prática Clínica como Assunto , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
19.
Presse Med ; 46(2 Pt 2): e41-e51, 2017 Mar.
Artigo em Francês | MEDLINE | ID: mdl-28256383

RESUMO

Tuberculosis (TB) continues to cause more deaths worldwide than any other single infectious disease. Even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. Since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regimen. This regimen is effective however it is pill burden, and duration has not received investment and innovation. Drug-resistant regimens are long and frequently poorly tolerated due to significant toxicity. This review is an update on what is new in the treatment of drug-susceptible and drug-resistant tuberculosis, new TB drugs currently being used and studied in clinical trials are also mentioned. Fortunately, there have been many significant advances in this field in recent years. The horizon is changing with the new WHO shorter multidrug-resistant tuberculosis regimens and with the increasing availability of new or repurposed drugs like bedaquiline, delamanid, clofazimine and linezolid. These drugs pose new challenges relating to their rational use to prevent selection of resistant strains of Mycobacterium tuberculosis even before a new regimen has been studied. The availability of these new drugs is offering hope and new possibilities for saving patients who had few or no treatment options. Their use and combination into effective regimens need to be studied; trials are in progress. It is hoped that soon we will be able to treat sensitive and drug-resistant cases with a universal regimen, this would revolutionise treatment and take us another step closer towards elimination.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose/tratamento farmacológico , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Gerenciamento Clínico , Reposicionamento de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Previsões , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Guias de Prática Clínica como Assunto , Seleção Genética , Terapias em Estudo , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Organização Mundial da Saúde
20.
Eur Respir J ; 49(3)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28331044

RESUMO

Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day-1 (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used).All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed. The effectiveness of clofazimine was assessed by comparing the treatment outcomes of patients undergoing clofazimine-containing regimens against those undergoing clofazimine-free regimens and its safety by describing clofazimine-attributed adverse events. A total of 1446 patients were treated with clofazimine-containing regimens and 1096 with pyrazinamide-containing regimens.Although success rates were similar in patients treated with clofazimine versus those treated with pyrazinamide (880 out of 1446, 60.9%, versus 708 out of 1096, 64.6%; p=0.054), clofazimine-treated cases exhibited higher death rates due to tuberculosis than pyrazinamide-treated ones (314 out of 1446, 21.7%, versus 120 out of 1096, 10.9%) but fewer failures (78 out of 1446, 5.4%, versus 95 out of 1096, 8.7%) and less loss to follow-up (144 out of 1446, 10.0%, versus 151 out of 1096, 13.8%). No relevant differences were detected when comparing adverse events in patients treated with clofazimine-containing regimens to those treated with clofazimine-free regimens. However, the incidence of side-effects was less than previously reported (gastro-intestinal complaints: 10.5%; hyper-pigmentation: 50.2%; neurological disturbances: 9-13%).


Assuntos
Antituberculosos/administração & dosagem , Clofazimina/administração & dosagem , Pirazinamida/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Antituberculosos/efeitos adversos , Brasil/epidemiologia , Clofazimina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
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