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1.
BMC Infect Dis ; 20(1): 678, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942990

RESUMO

BACKGROUND: Tuberculosis (TB) control is a primary global health priority but the goal to eliminate TB is being threatened by the increase in incidence of multidrug-resistant tuberculosis (MDR-TB). With this series of seven MDR-TB cases in migrant patients with identical Mycobacterium tuberculosis strains we aim to illustrate the challenges encountered during therapy and follow-up: language barriers, access to care for migrant patients, depression due to isolation, adverse reactions to the treatment, management of pediatric TB, further contact tracing. We also discuss best practices for the management of complex MDR-TB cases in settings with low overall TB incidence focusing on modern diagnostic assays and an individualized and an interdisciplinary therapeutic approach. METHODS: We describe a case series of seven consecutively diagnosed MDR-TB patients, six of them treated at our tertiary care hospital between May 2018 and March 2020. Epidemiologic data was gained by semi-structured patient interviews and reconstruction of the migration route. The origin of the cluster was confirmed by genotyping of the TB-strains. RESULTS: Six related patients were diagnosed with pulmonary MDR-TB between May and August 2018. All had a positive Interferon-Gamma-Release Assay (IGRA), in five patients sputum microscopy was positive for acid-fast bacilli (AFB). The genetic and phenotypical drug susceptibility test did not match with MDR-TB strains from an East-African origin. The index patient was identified through genetical fingerprinting. By changing the therapy to a modern MDR-TB regime and using an interdisciplinary and culture-sensitive approach, all patients improved clinically and radiologically. CONCLUSION: Human migration plays an important role for the global spread of MDR-TB in low incidence countries. Early case detection and adequate treatment are key to prevention of outbreaks. Especially language barriers and complex migration routes make genotyping of TB-strains a crucial tool to identify cases clusters, the potential index patient and transmission dynamics. We are fortunate enough to experience times in which new TB-antibiotics were made available and in which molecular assays revolutionized TB-diagnostics. We need to take advantage of that and develop personalized therapies for patients suffering from drug resistant TB.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Pré-Escolar , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo , Gravidez , Escarro/microbiologia , Sudão , Migrantes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
2.
PLoS One ; 15(8): e0236933, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866154

RESUMO

BACKGROUND: Persons living with human immunodeficiency virus (HIV) are at a greater risk of developing tuberculosis (TB) compared to people without HIV and of developing complications due to the complexity of TB/HIV coinfection management. METHODS: During 2013-2017, the Centers for Disease Control and Prevention (CDC) funded 5 TB Regional Training and Medical Consultation Centers (RTMCCs) (now known as TB Centers of Excellence or COEs) to provide medical consultation to providers for TB disease and latent TB infection (LTBI), with data entered into a Medical Consultation Database (MCD). Descriptive analyses of TB/HIV-related consultations were conducted using SAS® software, version [9.4] to determine the distribution of year of consultation, medical setting and provider type, frequency of consultations regarding a pediatric (<18 years) patient, and to categorize key concepts and themes arising within consultation queries and medical consultant responses. RESULTS: Of 14,586 consultations captured by the MCD in 2013-2017, 544 (4%) were categorized as TB/HIV-related, with 100 (18%) received in 2013, 129 (24%) in 2014, 104 (19%) in 2015, 117 (22%) in 2016, and 94 (17%) in 2017. Most TB/HIV consultations came from nurses (54%) or physicians (43%) and from local (65%) or state health departments (10%). Only 17 (3%) of HIV-related consultations involved pediatric cases. Off the 544 TB/HIV consultations, 347 (64%) concerned the appropriate treatment regimen for TB/HIV or LTBI/HIV for a patient on or not on antiretroviral therapy (ART). CONCLUSIONS: The data support a clear and ongoing gap in areas of specialized HIV knowledge by TB experts that could be supplemented with proactive educational outreach. The specific categories of TB/HIV inquiries captured by this analysis are strategically informing future targeted training and educational activities planned by the CDC TB Centers of Excellence, as well as guiding HIV educational efforts at regional and national TB meetings.


Assuntos
Centers for Disease Control and Prevention, U.S./economia , Infecções por HIV/complicações , Pessoal de Saúde/economia , Pessoal de Saúde/educação , Encaminhamento e Consulta/economia , Tuberculose/complicações , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Segurança , Tuberculose/tratamento farmacológico , Estados Unidos
3.
PLoS One ; 15(8): e0236264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750060

RESUMO

BACKGROUND: Extensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic. METHODS: A retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored. RESULTS: Of the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV-TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy. CONCLUSION: The new anti-tuberculosis drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.


Assuntos
Antituberculosos/administração & dosagem , Diarilquinolinas/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Anemia/epidemiologia , Antituberculosos/efeitos adversos , Efeitos Psicossociais da Doença , República Democrática do Congo/epidemiologia , Diarilquinolinas/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Exantema/induzido quimicamente , Exantema/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/epidemiologia , Adulto Jovem
4.
BMC Infect Dis ; 20(1): 576, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758169

RESUMO

BACKGROUND: China ranks second in the world in terms of numbers of tuberculosis (TB) cases and is one of the top three countries with the largest number of multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB). It also has high mortality and low cure rates of human immunodeficiency virus (HIV)-positive TB patients. This study aimed to analyse, under the integrated TB control model, the characteristics of TB patients seeking healthcare in the largest designated TB hospital in Chongqing. METHODS: This was a retrospective study of TB registers in a health facility. Record data of 1827 TB patients who had attended the Chongqing Public Health Medical Center (CPHMC) from 1 January to 31 December 2018 were included. The Statistical Package for Social Science (SPSS 18.0; IBM Corporation, Armonk, NY, USA) was used to analyse the data. Counting data were compared using the chi-square test or Fisher' s exact test. Among the results of the univariate analysis, the variables with statistical significance were included in the binomial stepwise logistic regression, with odds ratio and 95% confidence interval calculated. A two-tailed probability level of P < 0.05 was considered statistically significant. RESULTS: The majority of registered patients were men (1197), of Han ethnicity (1670), aged 21-60 years (1331), farmer/unemployed (1075), and living in county/district (1207). Approximately 24.9% of patients (455/1827) contracted DR-TB, 6% (110/1827) were co-infected with HIV, and 41.0% (749/1827) had drug-related hepatotoxicity. Among those patients, DR-TB was more likely to develop among farmers who received retreatment and had drug-related hepatotoxicity (P < 0.05). Women who received retreatment and lived in county/district were less likely to be HIV positive (P < 0.05). Compared with farmers, patients who were unemployed were more likely to be HIV positive, and those aged 21-60 years had a higher risk of being tested as HIV positive (P < 0.05). CONCLUSION: Farmers who received retreatment and had drug-related hepatotoxicity are more susceptible to DR-TB; young unemployed men have a higher risk of contracting HIV-positive TB. The demographic and clinical characteristics of TB patients should be taken into consideration in DR-TB and HIV-positive TB screening in the future.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Coinfecção/epidemiologia , HIV , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , China/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fazendeiros , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Desemprego , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 623, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831050

RESUMO

BACKGROUND: Non-adherence to tuberculosis (TB) treatment is the most important cause of poor TB outcomes, and improving support for TB patients is a primary priority for governments, but there has been little research on the effects of family, social and national policy support factors on TB treatment adherence. The current study evaluated treatment adherence among newly diagnosed TB patients in Dalian, north-eastern China, and determined the effects of family, society, and national policy support factors on treatment adherence. METHODS: A cross-sectional survey was conducted among newly diagnosed TB patients treated at the outpatient department of Dalian Tuberculosis Hospital from September 2019 to January 2020. Data were collected using a questionnaire that measured medication adherence, family support, social support, and national policy support and so on. Differences between groups were assessed using Chi-square tests and Fisher's exact tests. Ordinal logistic regression analysis was used to determine the predictors of adherence. RESULTS: A total of 481 newly diagnosed TB patients were recruited, of whom 45.7% had good adherence, and 27.4 and 26.8% had moderate and low adherence, respectively. Patients who had family members who frequently supervised medication (OR:0.34, 95% CI:0.16-0.70), family members who often provided spiritual encouragement (OR:0.13, 95% CI:0.02-0.72), a good doctor-patient relationship (OR:0.61, 95% CI:0.40-0.93), more TB-related knowledge (OR:0.49, 95% CI:0.33-0.72) and a high need for TB treatment policy support (OR:0.38, 95% CI:0.22-0.66) had satisfactory medication adherence. However, patients who had a college degree or higher (OR:1.69, 95% CI:1.04-2.74) and who suffered adverse drug reactions (OR:1.45, 95% CI:1.00-2.11) were more likely to have lower adherence. CONCLUSIONS: Our findings suggested that non-adherence was high in newly diagnosed TB patients. Patients who had family members who frequently supervised medication and provided spiritual encouragement and a good doctor-patient relationship and TB-related knowledge and a high need for policy support contributed to high adherence. It is recommended to strengthen medical staff training and patient and family health education and to increase financial support for improving adherence.


Assuntos
Política de Saúde , Adesão à Medicação , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , China , Estudos Transversais , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Apoio Social , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
6.
Drug Discov Ther ; 14(3): 135-138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669522

RESUMO

Drug-induced liver injury (DILI) due to anti-tubercular treatment (ATT) leads to increased morbidity and mortality in patients with tuberculosis (TB). The aim of this study was to find the impact of malnutrition on the development of DILI. This was a prospective cohort study (September 2017 to August 2019) in which all newly diagnosed in-patients with tuberculosis above the age of 18 years were included. Those patients with a body mass index (BMI) of < 18.5 kg/m2 were considered malnourished. The patients were monitored for the development of DILI. Liver function tests were done at the baseline (before initiation of ATT), on the third day and at discharge in all the patients. Chi-square tests and conditional multiple logistic analysis was performed to identify risk factors associated with DILI. Out of the 319 subjects who were enrolled, a total of 138 patents chose to follow up at our hospital. A total of 14 patients (10%) developed DILI. The median time to onset of DILI was found to be ten days. Extra-pulmonary TB, low BMI and high baseline liver enzyme levels had a significant association with the development of DILI (p < 0.05). Low serum albumin had increased odds ratio but wasn't statistically significant. Malnutrition is an important risk factor for TB-DILI.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Centros de Atenção Terciária/tendências , Adulto , Doença Hepática Induzida por Substâncias e Drogas/sangue , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Masculino , Desnutrição/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Tuberculose/sangue , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
7.
BMC Infect Dis ; 20(1): 294, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32664847

RESUMO

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in people living with HIV (PLHIV). HIV-infected children are at a higher risk of TB infection and disease compared to those without HIV. Isoniazid preventive therapy (IPT) is an effective intervention in preventing progression of latent TB infection to active TB. The World Health Organization (WHO) currently recommends that all children aged > 12 months and adults living with HIV in whom active TB has been excluded should receive a 6-months course of IPT as part of a comprehensive package of HIV care. Despite this recommendation, the uptake of IPT among PLHIV has been suboptimal globally. This study sought to determine the factors affecting IPT uptake and completion among HIV-infected children in a large HIV care centre in Nairobi, Kenya. METHOD: This was a cross-sectional mixed methods study comprising of quantitative and qualitative study designs. Medical records of 225 HIV-infected children aged 1 to < 10 years, in care in the Kenyatta National Hospital Comprehensive Care Centre (KNH CCC) were retrospectively reviewed, and 8 purposively selected healthcare providers and 18 consecutively selected caregivers of children were interviewed. RESULTS: IPT uptake among CLHIV in care in the KNH CCC was 68% (152/225) while the treatment completion rate was 82% (94/115). IPT-related health education and counselling were the main facilitators of IPT uptake and completion, while fear of adverse drug reaction, pill burden and lack of an integrated monitoring and evaluation system for IPT were the major barriers. CONCLUSION: The IPT uptake in this study was low and fell short of the set global target of > 90%. The completion rate was however acceptable. There is an urgent need to address the identified barriers.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/prevenção & controle , Adulto , Antituberculosos/efeitos adversos , Criança , Pré-Escolar , Aconselhamento , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Lactente , Isoniazida/efeitos adversos , Quênia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Pesquisa Qualitativa , Encaminhamento e Consulta , Estudos Retrospectivos , Resultado do Tratamento , Recusa do Paciente ao Tratamento
8.
PLoS One ; 15(7): e0236109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692774

RESUMO

BACKGROUND: Pyrazinamide (PZA) is a common drug that causes serious adverse events (SAEs). The aim of this study was to determine the incidence of and risk factors for SAEs due to PZA during first-line anti-tuberculosis treatment. METHODS: The medical records of patients with tuberculosis (TB) treated with PZA-containing regimens including first-line drugs-ethambutol, rifampicin, and isoniazid-from January 2003 to June 2016 were reviewed. SAEs were defined as side effects that led to drug discontinuation. The causative drug was determined based on the disappearance of the SAEs upon drug withdrawal and/or the recurrence of the same SAEs with re-challenge. RESULTS: Of 2,478 patients with TB, 16.4% experienced SAEs. The incidence of SAEs increased significantly as age increased, except with rifampin. PZA accounted for most SAEs (55.8%). Hepatotoxicity was the most common SAE due to PZA (44.5%), followed by gastrointestinal (GI) intolerance (23.8%). The risk of SAEs due to PZA increased significantly as age increased, when sex and comorbidities were adjusted (odds ratio, 1.013; 95% confidence interval, 1.004-1.023; P = 0.007). In the subgroup analysis, older age was an independent risk factor for GI intolerance but not for hepatotoxicity. CONCLUSION: PZA was the most common drug associated with SAEs among the first-line anti-TB drugs, and old age was an independent factor for SAE occurrence. This study suggests that the early recognition of whether the causative agent is PZA may improve effective treatment compliance, particularly in elderly patients.


Assuntos
Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/efeitos adversos , Tuberculose/tratamento farmacológico , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tuberculose/microbiologia
9.
Medicine (Baltimore) ; 99(21): e20012, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481268

RESUMO

INTRODUCTION: Paradoxical reaction in tuberculosis (TB) is defined as the reappearance of general symptoms, aggravation of pre-existing diseases, or appearance of new lesions despite adequate anti-TB therapy. It may result from the hyperactivity of the immune response, resulting in an intense inflammation. There are few cases of vertebral TB reported as paradoxical reaction, mainly among immunocompetents patients. PATIENT CONCERNS: We describe a male immunocompetent patient with confirmed pulmonary and meningeal TB. He was readmitted after 60 days of adequate treatment, with vertebral TB and paravertebral abscess, despite clinical improvement of the other locations. We defined as an uncommon case of a paradoxical reaction, confirmed by nuclear magnetic resonance and molecular rapid test for TB. DIAGNOSIS: Mycobacterium tuberculosis (MTB) was detected in cerebrospinal fluid by molecular rapid test (Gene Xpert MTB/ rifampicina method). Sputum research and culture were positive for the same agent. Lumbosacral spine nuclear magnetic resonance revealed bone destruction from T8 to T11, and a paravertebral collection was found. Gene Xpert MTB/rifampicina and culture were positive for M tuberculosis in the drained material of the paravertebral abscess. INTERVENTIONS: The paravertebral abscess was drainage by tomography-guided. Treatment with 4 anti-TB drugs was extended for 60 days and 2 anti-TB drugs was maintained for 10 months. There was a complete clinical improvement. OUTCOME: After draining the paravertebral abscess, the patient progressively improved and was discharged for outpatient follow-up. He was on antituberculous drugs for 1 year; subsequently, complete resolution of the infection was reported. CONCLUSION: Paradoxical reaction may be a difficult diagnosis in immunocompetent patient. Vertebral TB as a paradoxical reaction is an uncommon presentation. Therapeutic failure or resistance to treatment should be ruled out to confirm the diagnosis of paradoxical reaction.


Assuntos
Antituberculosos/efeitos adversos , Imunocompetência/efeitos dos fármacos , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose da Coluna Vertebral/etiologia , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Sacro/diagnóstico por imagem , Sacro/patologia , Tuberculose Meníngea/complicações , Tuberculose Pulmonar/classificação , Tuberculose da Coluna Vertebral/líquido cefalorraquidiano
10.
PLoS One ; 15(6): e0234651, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544174

RESUMO

BACKGROUND: Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath. OBJECTIVE: We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients. METHODS: A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component. RESULTS: Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients' home for optimal care. CONCLUSION: Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Imipenem/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Instituições de Assistência Ambulatorial/normas , Antituberculosos/efeitos adversos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/complicações , Feminino , Serviços de Assistência Domiciliar/normas , Humanos , Imipenem/efeitos adversos , Imipenem/normas , Índia , Controle de Infecções/normas , Masculino , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Dispositivos de Acesso Vascular , Vômito/induzido quimicamente
11.
Infect Dis Poverty ; 9(1): 50, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381098

RESUMO

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.


Assuntos
Antituberculosos/uso terapêutico , Medicina Tradicional Chinesa/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento/estatística & dados numéricos , Comprimidos , Tuberculose Pulmonar/patologia , Adulto Jovem
12.
Medicine (Baltimore) ; 99(16): e19567, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311924

RESUMO

OBJECTIVE: To evaluate the differences between traditional Chinese medicine combined with western medicine and western medicine alone for the treatment of secondary tuberculosis and its impact on the evaluation of clinical efficacy and safety of patients in randomized controlled trials. METHODS: A literature search of all major academic databases was conducted (PubMed, CNKI, Wanfang, VIP). Meta-analysis was conducted using RevMan 5.3 and Stata 12.0 software for those studies that satisfied the inclusion criteria. Ethical approval was not necessary because no people or animals were selected as subjects in this meta-analysis. RESULTS: Twenty-three randomized controlled trials were included in this meta-analysis. The following indicators in the treatment group (traditional Chinese medicine decoction combined with western medicine chemotherapy) improved in comparison with those in the control group:focus absorption rate (RR:1.18; 95% CI: 1.15-1.22);sputum smear negative rate (RR: 1.17; 95% CI: 1.09-1.27);comprehensive clinical effective rate (RR: 1.18; 95% CI: 1.14-1.22);cavity closure rate (RR: 1.37; 95% CI: 1.12-1.67).The difference of Immune function indicator likes CD4+ level (SMD: 0.76; 95% CI: -0.25 to 1.76) between the treatment group and the control group was not significant. In addition, safety evaluation indicators like the decrease rate of white blood cell (WBC) and platelets (PLT) and the elevation rate of alanine aminotransferase (ALT) and uric acid (UA) in the treatment group were reduced compared with those in the control group (P < .05). CONCLUSIONS: The curative effect of combining traditional Chinese and western medicine for the treatment of secondary tuberculosis is better than that of western medicine alone and is conducive to reducing the incidence of adverse reactions.


Assuntos
Antituberculosos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Alanina Transaminase/sangue , Antituberculosos/efeitos adversos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Fitoterapia , Contagem de Plaquetas , Ensaios Clínicos Controlados Aleatórios como Assunto , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/imunologia , Ácido Úrico/sangue
14.
Yi Chuan ; 42(4): 374-379, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32312706

RESUMO

To systematically study the susceptible genetic markers for liver injury induced by anti-tuberculosis drugs in the Chinese population, 109 genes related to drug metabolism, transport and immunity were captured by Haloplex capture technique from DNA samples of 41 patients with liver injury induced by anti-tuberculosis drugs and 39 healthy controls, and sequenced completely. Association study was conducted using Plink software. To verify the significant candidate SNPs, the χ 2 study was expanded to the control group from the 1000-person Genome Project of the East Asian population. SIFT and Polyphen2 software were used to predict the functional significance of the associated SNPs. Our results identified the UGT1A4 rs2011404 (χ 2 = 4.6809, P = 0.0305) as a susceptible genetic marker for liver injury induced by anti-tuberculosis drugs, and rs2011404 mutation might contribute to UGT1A4 protein dysfunction. This study has provided a potentially useful reference for establishing the precision medicine in rational uses of anti-tuberculosis drugs in the clinic.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/genética , Marcadores Genéticos , Predisposição Genética para Doença , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Glucuronosiltransferase/genética , Humanos , Polimorfismo de Nucleotídeo Único , Tuberculose/tratamento farmacológico
16.
Med Sci Monit ; 26: e920350, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145061

RESUMO

BACKGROUND The aim of this study was to investigate the clinical characteristics and the risk factors associated with anti-tuberculosis (anti-TB) drug-induced liver injury (DILI). MATERIAL AND METHODS This retrospective study enrolled 140 hospitalized patients diagnosed with anti-TB DILI during January 2009 to December 2015. We assessed the baseline characteristics and performed regular follow-up up to the 24th week to assess the possible risk factors associated with the condition. RESULTS The study population was 58.6% male and 41.4% female patients; 20.7% were diagnosed with grades 4-5 DILI and 79.3% with grades 1-3 DILI. Female patients were significantly more likely to be diagnosed with grades 4-5 DILI than with grades 1-3 DILI (58.6% vs. 36.9%, p=0.036). Patients treated with a multidrug anti-TB regimen were more commonly affected with grades 4-5 DILI (86.2% vs. 68.5%, p=0.045). A significant number of patients who reinitiated anti-TB therapy suffered severe liver injury in comparison to patients with grades 1-3 DILI (41.4% vs. 10.8%, P<.001). Laboratory examinations revealed significantly higher values for total bilirubin (TBL), International normalized ratio (INR), and Hy's law (P<.001) in the grades 4-5 group compare to the grades 1-3 group. CONCLUSIONS Female gender, combination therapy for antitubercular drugs (isoniazid, rifampicin and pyrazinamide), re-challenge were the risk factors associated with the severity of anti-TB DILI.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirazinamida/efeitos adversos , Pirazinamida/uso terapêutico , Estudos Retrospectivos , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Fatores de Risco , Tuberculose/tratamento farmacológico , Adulto Jovem
17.
Lancet Respir Med ; 8(4): 383-394, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32192585

RESUMO

BACKGROUND: Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens. METHODS: We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug. FINDINGS: 58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed. INTERPRETATION: Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis. FUNDING: Canadian Institutes of Health Research, Centers for Disease Control and Prevention (USA), American Thoracic Society, European Respiratory Society, and Infectious Diseases Society of America.


Assuntos
Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Ácido Aminossalicílico/efeitos adversos , Canadá/epidemiologia , Clofazimina/efeitos adversos , Diarilquinolinas/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Fluoroquinolonas/efeitos adversos , Humanos , Incidência , Linezolida/efeitos adversos , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologia
18.
N Engl J Med ; 382(10): 893-902, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32130813

RESUMO

BACKGROUND: Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes. METHODS: In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs - bedaquiline, pretomanid, and linezolid - that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated. RESULTS: A total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid. CONCLUSIONS: The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed. (Funded by the TB Alliance and others; ClinicalTrials.gov number, NCT02333799.).


Assuntos
Antituberculosos/administração & dosagem , Diarilquinolinas/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Linezolida/administração & dosagem , Nitroimidazóis/administração & dosagem , Administração Oral , Adolescente , Adulto , Antituberculosos/efeitos adversos , Carga Bacteriana , Diarilquinolinas/efeitos adversos , Quimioterapia Combinada , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Análise de Intenção de Tratamento , Linezolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Nitroimidazóis/efeitos adversos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
19.
BMJ Case Rep ; 13(1)2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32014989

RESUMO

We present a case of a young Asian female with rheumatoid arthritis who received latent tuberculosis infection (LTBI) treatment prior to treatment with a biologic agent, and developed shock with resistant hypotension on re-exposure to rifampicin. We discuss the epidemiology, pathophysiology and management of rifampicin induced shock, concluding that clinicians should be aware of this rare, but potential adverse effect, and be aware that adverse reactions to rifampicin are more frequent during re-exposure or longer dosing interval regimes. The evidence for desensitisation following such a reaction is lacking and this approach is not currently recommended. We would suggest close collaboration between specialties prescribing immunosuppression and the tuberculosis team when LTBI treatment is required after a reaction, with patient involvement to discuss the risks and benefits of treatment options.


Assuntos
Antituberculosos/efeitos adversos , Hipotensão/induzido quimicamente , Tuberculose Latente/tratamento farmacológico , Rifampina/efeitos adversos , Choque Séptico/induzido quimicamente , Adulto , Feminino , Hidratação , Humanos , Hipotensão/diagnóstico , Hipotensão/terapia , Retratamento , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
20.
Curr Pharm Biotechnol ; 21(10): 939-947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101120

RESUMO

BACKGROUND: The development of multidrug-resistant tuberculosis (MDR-TB) poses a considerable threat to tuberculosis control programmes in Nigeria. There is an increase in the prevalence of MDR-TB worldwide both among new tuberculosis cases as well as previously-treated ones. There is also a rise in transmission of resistant strains due to an increase in MDR-TB patients largely due to the poor drug compliance and the impact of Human immunodeficiency virus infection. Therefore, we intend to determine the extent of MDR-TB among attendees of chest clinics in Osun-State, Nigeria. OBJECTIVES: The objective of this study was to determine the prevalence of MDR-TB among confirmed tuberculosis patients attending chest clinics in Osun-State, Nigeria. METHODS: This study was conducted among 207 attendees of chest clinics in Osun-State between June, 2015 and October 15, 2016. Sputum and blood samples of the participants were collected. GeneXpert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. Sputum samples were cultured on Lowenstein-Jensen (L-J) medium using N-acetyl-Lcysteine- sodium hydroxide (NALC-NaOH) decontamination method. Drug susceptibility testing (DST) to three first-line drugs was carried out using the proportion DST method. RESULTS: The prevalence of MTB was found to be 27.5% while the prevalence of MDR-TB from the fifty-seven isolates was 10.5%. Previously treated and new cases had a prevalence of 7.0% and 3.5% MDR-TB, respectively. Seventy (33.8%) participants were positive for HIV infection, out of which twenty-six (12.6%) had co-infection of tuberculosis and HIV. The mono-resistance rates of the three first-line drugs used were: 5.3% and 8.7% for ethambutol (EMB) and isoniazid (INH), respectively. No isolate had mono-resistance (0%) to rifampicin (RIF). CONCLUSION: This study observed the prevalence of 27.5% MTB and a prevalence of 10.5% MDR-TB among the MTB isolates. The prevalence of TB is high in Osun State. MDR-TB prevalence is higher compared with the national estimate of MDR-TB (5.1%) of 2017. Resistant TB is a threat to national tuberculosis control and it is recommended that all the facilities be equipped to cater to its diagnosis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Nigéria/epidemiologia , Prevalência , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
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