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1.
Trials ; 22(1): 651, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563240

RESUMO

BACKGROUND: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. METHODS: endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. DISCUSSION: The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.


Assuntos
Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Teorema de Bayes , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifampina/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
2.
J Int Med Res ; 49(9): 3000605211043239, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34525861

RESUMO

A 39-year-old woman was admitted to our hospital on 19 January 2019 because of a 10-day history of intolerance to oils in her food, fatigue, and yellowing of the skin and sclera. In December 2018, the patient had been diagnosed with tuberculous pleurisy at a local hospital and received quadruple anti-tuberculosis treatment. Ten days before presentation to our hospital, she had developed anorexia, fatigue, nausea, loss of appetite, cough, and shortness of breath. She visited a local hospital, where she was considered to have drug-induced hepatitis. She discontinued the anti-tuberculosis drugs and liver protection treatment. After 3 days, her symptoms had not substantially improved. She visited the infection department of our hospital for further diagnosis and treatment. After 6 days of treatment, the patient's symptoms were not significantly improved, her liver and muscle enzyme concentrations were further increased, and her limbs had become weaker and more difficult to move. We considered diagnoses of drug-induced hepatitis and drug-induced myopathy. The patient was treated with intravenous methylprednisolone at 40 mg once a day for 16 days and other symptomatic treatments. Her symptoms significantly improved and she was discharged.


Assuntos
Doenças Musculares , Preparações Farmacêuticas , Tuberculose Pleural , Corticosteroides/uso terapêutico , Adulto , Antituberculosos/efeitos adversos , Feminino , Humanos
3.
BMC Infect Dis ; 21(1): 834, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412615

RESUMO

BACKGROUND: To verify the efficacy and safety of an inexpensive standardized regimen for multidrug-resistant tuberculosis (MDR-TB) with low resistance to isoniazid (INH), a multicenter prospective study was conducted in eastern China. METHODS: Patients diagnosed as MDR-TB with low concentration INH resistance and rifampicin resistance, second-line/injectable agents sensitive were prospectively enrolled, given the regimen of Amikacin (Ak)-Fluoroquinolones (FQs)-Cycloserine (Cs)-Protionamide (Pto)-PasiniaZid (Pa)-Pyrazinamide (Z) for 6 months followed by 12 months of FQs-Cs-Pto-Pa-Z, and then followed up for treatment outcomes and adverse events (AEs). RESULTS: A total of 114 patients were enrolled into the study. The overall favorable treatment rate was 79.8% (91/114). Among 91 cases with favorable treatment, 75.4% (86/114) were cured and 4.4% (5/114) were completed treatment. Regarding to unfavorable outcomes, among 23 cases, 8.8% (10/114) had failures, 8.8% (10/114) losing follow up, 0.9% (1/114) had treatment terminated due to intolerance to drugs and 1.8% (2/114) died. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients (26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42). CONCLUSIONS: The regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population, especially for newly-treated patients, which could be expected to be developed into a short-course regimen. Clinical trials registration China Clinical Trial Registry ChiCTR-OPC-16009380.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , China , Humanos , Estudos Prospectivos , Pirazinamida , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
4.
Int J Infect Dis ; 111: 138-147, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454119

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) patients have been suffering long, ineffective, and toxic treatment until short-course injectable-free regimens emerged. However, the new WHO-recommended regimens might be less feasible in the real-world setting. Here, we evaluated two optimized all-oral short-course regimens in China. METHODS: From April 2019 to August 2020, we conducted a prospective nonrandomized controlled trial and consecutively included 103 MDR-TB patients diagnosed with pulmonary MDR-TB in Shenzhen, China. A 4-5 drug regimen of 9-12 months was tailored to the strain's resistance patterns, patients' affordability, and tolerance to drugs. This was an interim analysis, focusing on the early treatment period. RESULTS: 53.4% (55/103) of patients were prescribed linezolid, fluoroquinolone (FQ), clofazimine, cycloserine, and pyrazinamide, followed by a regimen in which clofazimine was replaced by bedaquiline (35/103, 34.0%). The culture conversion rate was 83.1% and 94.4% at two and four months, respectively, with no significant difference between bedaquiline-free and bedaquiline-containing cases and between FQ-susceptible and FQ-resistant cases. Among 41 patients who completed treatment, 40 (97.6%) patients had a favorable outcome and no relapse was observed. Peripheral neuropathy and arthralgia/myalgia were the most frequent AEs (56.3%, 58/103). 18 AEs caused permanent discontinuation of drugs, mostly due to pyrazinamide and linezolid. CONCLUSION: Optimized all-oral short-course regimens showed satisfactory efficacy and safety in early treatment stage. Further research is needed to confirm these results.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Diarilquinolinas/efeitos adversos , Humanos , Estudos Prospectivos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
5.
Pan Afr Med J ; 39: 73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422196

RESUMO

Niacin or tryptophan deficiency causes pellagra. Isoniazid interferes with the absorption of niacin and individuals on Isoniazid (INH) are at risk of pellagra. Isoniazid preventive therapy (IPT) is the administration of isoniazid to immunosuppressed individuals to prevent active tuberculosis (TB). IPT, in sub-Saharan Africa, the region worst hit by HIV and with a high TB prevalence, is recommended. A 40-year-old, HIV+ Zambian woman on Antiretroviral therapy for five years and IPT for three months presented with a four-day history of constipation, generalised body weakness and irrelevant talk. She complained of a generalised rash, sloughing off, and darkening of the skin on the face, neck, forearms, and dorsum of both feet. A physical examination revealed features of pellagra, and rapid response to oral niacin reaffirmed the diagnosis of pellagra. Unlike typical cases of pellagra presenting with the classic 3 Ds of Diarrhoea, Dementia and Dermatitis, our patient presented with constipation instead of diarrhoea. A consideration of Pellagra in HIV+ patients on IPT whose diet is mostly maize-based will be beneficial, even if the classic 3 Ds of diarrhoea, dementia, and dermatitis are not wholly present. A timely diagnosis and prompt treatment of pellagra can be lifesaving.


Assuntos
Antituberculosos/efeitos adversos , Isoniazida/efeitos adversos , Pelagra/induzido quimicamente , Adulto , Fármacos Anti-HIV/administração & dosagem , Antituberculosos/administração & dosagem , Constipação Intestinal/etiologia , Demência/etiologia , Dermatite/etiologia , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Isoniazida/administração & dosagem , Niacina/administração & dosagem , Niacina/deficiência , Pelagra/diagnóstico , Tuberculose/prevenção & controle
7.
Chem Commun (Camb) ; 57(63): 7842-7845, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34278391

RESUMO

A turn-on optoacoustic and NIR-II fluorescent probe for imaging antituberculotic drug-induced liver injury has been developed. Probe TC-H2O2 responds to hepatic H2O2, thus releasing chromophore TC-NN, which displays prominent NIR-II fluorescence and optoacoustic signals for diagnosing liver injury.


Assuntos
Antituberculosos/análise , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Corantes Fluorescentes/química , Imagem Óptica , Técnicas Fotoacústicas , Animais , Antituberculosos/efeitos adversos , Raios Infravermelhos , Camundongos , Estrutura Molecular , Células RAW 264.7
8.
Am J Case Rep ; 22: e930828, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34267172

RESUMO

BACKGROUND Antituberculosis drug-induced hepatotoxicity (ADIH) is a possible adverse event of antitubercular treatment. There are still no official guidelines for ADIH management in children. Recurrent ADIH is infrequently reported. CASE REPORT In this article, we report 6 unusual cases of recurrent ADIH in children. Five children developed ADIH during the intensive phase. Streptomycin and ethambutol were given to those with tuberculosis meningitis, urinary tract tuberculosis, and one patient with pulmonary tuberculosis with HIV infection and cardiac comorbidities. Five patients experienced a second ADIH episode after reintroduction. One patient developed ADIH symptoms again before reaching a full dose of isoniazid. The patient with pulmonary tuberculosis, HIV infection, and dilated cardiomyopathy experienced secondary episodes of ADIH and received levofloxacin and ethambutol as additional drugs. CONCLUSIONS Recurrent ADIH is relatively uncommon in children but may be encountered in daily practice. Reintroduction of previous treatment regimens should be tailored individually. There is an urgent need for standardized guidelines for ADIH in children.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Isoniazida , Recidiva Local de Neoplasia/tratamento farmacológico
9.
Gan To Kagaku Ryoho ; 48(7): 959-962, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267036

RESUMO

An 86-year-old man was referred to our hospital with pulmonary tuberculosis developed during postoperative chemotherapy for gastric cancer. We initiated treatment with an anti-tuberculosis drug. Following confirmation of the effectiveness of this regimen, we combined the treatment with anti-cancer drugs. Tuberculosis treatment was completed without any drug interactions or serious side effects due to multidrug administration. For cancer patients who developed tuberculosis, combination treatment requires careful observation; however, it is a treatment option that can control both diseases.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Tuberculose Pulmonar , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antituberculosos/efeitos adversos , Humanos , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tuberculose Pulmonar/tratamento farmacológico
10.
Int J Infect Dis ; 110: 179-186, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34293490

RESUMO

OBJECTIVES: To determine the safety and efficacy of bedaquiline for Chinese patients with multidrug-resistant tuberculosis (MDR-TB) based on serum concentration monitoring and to identify factors associated with QTc prolongation occurring during treatment. METHODS: Data were collected from 35 patients who received treatment regimens containing bedaquiline for MDR-TB from May 2018 to December 2020. Blood samples were collected, and serum concentrations of bedaquiline were measured using high-performance liquid chromatography-mass spectrometry. RESULTS: After completing the 24-week bedaquiline treatment course, 80.0% of the patients' sputum cultures turned negative. The median time to sputum culture conversion was 75.5 days (interquartile range 52-126 days). The mean serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during treatment and 0.205 ± 0.145 µg/ml at 16 weeks after bedaquiline discontinuation. Bedaquiline remained detectable 52 weeks after discontinuation. Combination with clofazimine during bedaquiline treatment significantly increased cardiac QTc prolongation. When QTc prolongation occurred, serum potassium levels decreased by 10.71% from baseline, while serum sodium levels increased by 1.07% from baseline. CONCLUSIONS: Good treatment outcomes were obtained with bedaquiline treatment in Chinese patients with MDR-TB. Combination with clofazimine increased the risk of QTc prolongation. Serum electrolytes (potassium and sodium) should be measured regularly during treatment of MDR-TB with regimens containing bedaquiline.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , China , Diarilquinolinas/efeitos adversos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
11.
Front Immunol ; 12: 661934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276654

RESUMO

Background: Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown. Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes. Results: Among 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]). Conclusion: Increased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.


Assuntos
Antituberculosos/uso terapêutico , Neutrófilos/imunologia , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Adulto , Antituberculosos/efeitos adversos , Brasil , Feminino , Humanos , Contagem de Leucócitos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Pulmonar
12.
Ann Palliat Med ; 10(6): 6518-6534, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34154362

RESUMO

BACKGROUND: Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although chemotherapy drugs are widely used in the treatment of TB, and achieved good results, but the side effects, especially anti-tuberculosis drug-induced liver injury (ATDILI), cannot be overlooked. Many researchers have made efforts to uncover the association of cytochrome P450 (CYP) enzyme genetic polymorphisms with ATDILI. In this study, we systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to ATDILI. METHODS: We carried out literature searches of PubMed, Ovid, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI). Medical Subject Headings (MeSH) terms including "cytochrome P450 enzyme", "drug-induced liver injury", "polymorphism", "tuberculosis", and "hepatotoxicity" were used as keywords for our searches. RESULTS: The pooled odds ratio (OR) of all studies for CYP2E1 to the risk of ATDILI was 1.18 [95% confidence interval (CI): 0.82-1.71]. The articles in this meta-analysis were observed to be mildly heterogeneous. Further subgroup analysis revealed that the patients who receiving a four-drug protocol (INH + RIF + PZA + EMB) or three-drug protocol (INH + RIF + PZA) regimens showed a higher risk of ATDILI than those who receiving INH alone. However, subgroup analyses according to participants' ethnic origin, study type, and the definition of ATDILI produced no statistically significant results. Associations between other genes in the CYP family and ATDILI were indistinct and equivocal. DISCUSSION: Our meta-analysis has uncovered an association between CYP2E1 RsaI/PstI polymorphisms and ATDILI, especially among patients who receive a four-drug (INH + RIF + PZA + EMB) or three-drug (INH + RIF + PZA) anti-TB treatment regimen.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Tuberculose , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Sistema Enzimático do Citocromo P-450/genética , Humanos , Polimorfismo Genético/genética , Tuberculose/tratamento farmacológico
13.
BMC Infect Dis ; 21(1): 510, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059022

RESUMO

OBJECTIVE: To determine the prevalence of Latent Tuberculosis in patients with hematological neoplasms at the Instituto Nacional de Cancerología in Mexico City using the Tuberculin skin test (TST). METHODS: This retrospective study included all patients with a recent diagnosis of hematological neoplasms who were admitted for treatment from 2017 to 2018 and who were screened for latent tuberculosis with the TST. The prevalence of latent tuberculosis in this group, tolerance and therapeutic adherence in treated patients are described. RESULTS: The files of 446 patients with hematological malignancy who had a TST were reviewed. The prevalence of latent tuberculosis was 31.2% (n = 139). Ninety-three patients received isoniazid, 15.1% had some adverse reactions, but only 4 (4.3%) had to discontinue treatment. Two patients with latent tuberculosis under treatment with Isoniazid reactivated tuberculosis infection. CONCLUSIONS: The prevalence in our study was within the range of other similar Mexican populations. Isoniazid treatment had an adequate tolerance and adherence. Longer follow-up could offer more information on the risk of reactivation in both groups.


Assuntos
Neoplasias Hematológicas/epidemiologia , Tuberculose Latente/epidemiologia , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Institutos de Câncer , Feminino , Neoplasias Hematológicas/microbiologia , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Prevalência , Estudos Retrospectivos , Teste Tuberculínico , Tuberculose/epidemiologia , Tuberculose/etiologia
14.
J Infect ; 83(1): 27-36, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34015383

RESUMO

Objectives estimate the prevalence of ototoxic hearing loss in drug-resistant tuberculosis (DR-TB) patients treated with aminoglycoside antibiotics via a systematic review and meta-analysis. Estimate the annual preventable cases of hearing loss in DR-TB patients and leverage findings to discuss primary, secondary and tertiary prevention. Methods studies published between 2005 and 2018 that reported prevalence of post-treatment hearing loss in DR-TB patients were included. We performed a random effects meta-analysis to determine pooled prevalence of ototoxic hearing loss overall and by medication type. Preventable hearing loss cases were estimated using World Health Organization (WHO) data on DR-TB treatment and prevalence determined by the meta-analysis. Results eighteen studies from 10 countries were included. Pooled prevalence of ototoxic hearing loss and the corresponding 95% confidence interval (CI) was 40.62% CI [32.77- 66.61%] for all drugs (kanamycin: 49.65% CI [32.77- 66.61%], amikacin: 38.93% CI [26.44-53.07%], capreomycin: 10.21% CI [4.33-22.21%]). Non-use of aminoglycosides may result in prevention of approximately 50,000 hearing loss cases annually. Conclusions aminoglycoside use results in high prevalence of ototoxic hearing loss. Widespread prevention of hearing loss can be achieved by following updated WHO guidelines for DR-TB treatment. When hearing loss cannot be avoided, secondary and tertiary prevention should be prioritized.


Assuntos
Perda Auditiva , Tuberculose Resistente a Múltiplos Medicamentos , Aminoglicosídeos/efeitos adversos , Antituberculosos/efeitos adversos , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia , Humanos , Prevalência , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
15.
Trials ; 22(1): 355, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016158

RESUMO

BACKGROUND: The risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda. METHODS: The Drinkers' Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression. DISCUSSION: This study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence. TRIAL REGISTRATION: ClinicalTrials.gov NCT03492216 . Registered on April 10, 2018.


Assuntos
Infecções por HIV , Tuberculose , Adulto , Antituberculosos/efeitos adversos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Isoniazida/efeitos adversos , Motivação , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Uganda
16.
Transpl Infect Dis ; 23(4): e13659, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34057810

RESUMO

Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis that is resistant to isoniazid and rifampicin (Rif). The use of immunosuppressive drugs in solid organ transplant recipients can increase the risk of TB. Management of MDR-TB is quite challenging in the general population with poor compliance owing to lengthy treatment duration and drug toxicities. New drugs as well as shorter regimen have been used to increase the likelihood of adherence. The experience of treating MDR-TB in the transplant recipients is limited. New drugs like bedaquiline, linezolid, clofazimine, and delamanid have rarely been used in transplant recipients. To the best of our knowledge, only 14 cases of MDR-TB in transplant population have been reported in the literature and no case from Pakistan, a high TB burden country. We are reporting our experience of treating 4 renal transplant recipients. We used new drug regimen and found many side effects. Treatment outcome was successful with complete cure in 3 of our patients, however one died of severe drug toxicity. The most worrisome drug interaction was between azathioprine and linezolid, with life-threatening thrombocytopenia. There was no graft dysfunction noted at the end of the therapy. The management of MDR-TB in transplant recipients is challenging; excellent coordination between transplant team and Infectious Diseases Physician for close monitoring and follow-up is needed.


Assuntos
Transplante de Rim , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Humanos , Transplante de Rim/efeitos adversos , Transplantados , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
17.
N Engl J Med ; 384(18): 1705-1718, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33951360

RESUMO

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antituberculosos/uso terapêutico , Moxifloxacina/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Intervalos de Confiança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Moxifloxacina/efeitos adversos , Rifampina/efeitos adversos , Adulto Jovem
18.
Stud Health Technol Inform ; 281: 784-788, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042685

RESUMO

BACKGROUND: Hepatotoxicity is very frequent and is a dangerously adverse effect of anti-TB medications. This effect can reduce the effectiveness of the treatment by compromising treatment regimens. Among these first-line quadruple therapy drugs (INH, RMP, PZA, and EMB), INH, RMP, and PZA are metabolized mostly by the liver, and due to this, are likely hepatotoxic. However, the survival times of hepatotoxicity among patients with TB in Thailand are currently not available. The aims of the present study were to assess the prevalence and survival time of drug-induced hepatotoxicity in patients with TB. METHODS: A cross-sectional retrospective study was performed to explore the survival time of the development of drug-induced hepatotoxicity among 327 patients with TB who received standard drug treatment at the TB clinic in Phichit Hospital. Data was collected from the HOSxP program and medical records from 2016 to 2018. Kaplan-Meier and Cox's regressions were used for data analysis. RESULTS: The results showed that prevalence of drug-induced hepatotoxicity was 6.42% and confirmed that patients with TB who were <50 years of age will be a median survival time on drug-induced hepatotoxicity is 17 days and 30 days for those who age group ≥50 years. CONCLUSION: The median survival time of drug-induced hepatotoxicity among patients with TB who were <50 years of age is 17 days. So, patients with TB whose ages are less than 50 years should receive liver function tests such as AST and ALT and investigate risk behavior before receiving the anti- TB treatment.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Preparações Farmacêuticas , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Tailândia/epidemiologia
19.
Clin Chim Acta ; 519: 153-162, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33932406

RESUMO

BACKGROUND AND AIMS: To assess the relevance of the slow acetylator phenotype based on NAT2 genotypes, among patients with pulmonary tuberculosis (PTB) that developed hepatotoxicity after first-line tuberculosis treatment in a Northeastern Mexican population. METHODS: Ninety one PTB patients were included, 7 of them developed hepatotoxicity. NAT2 SNPs (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931) were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using Epi Info statistical software 7.0 and SHEsisPlus for haplotype reconstruction. The NAT2 slow non-synonymous SNP were studied by molecular dynamic analysis (MDA). RESULTS: The frequency of the haplotype associated with slow acetylation status for PTB was 58%, and for with hepatotoxicity (PTB-H) represented 42.6%. Three haplotypes, NAT2*5Q, NAT2*5U, NAT2*5Va were exclusively present in seven PTB-H patients, (P = 0.01, P = 0.0006, P = 0.01, respectively). These haplotypes include the combination of two SNPs (I114T + R197Q or I114T + G286E). The effect of the SNPs on protein structure is to disrupt the CoA binding site affecting acetylation activity. CONCLUSION: Our study provides insight into slow acetylation NAT2 haplotypes associated with hepatotoxicity after first-line tuberculosis treatment, for first time, in a Mexican population. The molecular mechanism acts at the CoA binding site.


Assuntos
Arilamina N-Acetiltransferase , Doença Hepática Induzida por Substâncias e Drogas , Tuberculose , Antituberculosos/efeitos adversos , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Genótipo , Humanos , Estrutura Molecular , Polimorfismo de Nucleotídeo Único , Tuberculose/tratamento farmacológico , Tuberculose/genética
20.
Pan Afr Med J ; 38: 191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995797

RESUMO

Introduction: tuberculosis (TB) remains a global major health problem, especially in developing countries. Although treatment regimen for TB has been highly effective, treatment-related adverse effects account for significant morbidity leading to reduced effectiveness of therapy and high default rate. This study evaluated the nature and occurrence of Adverse Drug Reactions (ADRs) in patients receiving first line antitubercular therapy (ATT) in Tamale Teaching Hospital (TTH) and its effects on adherence. Methods: the study was a cross-sectional study for a period of six months. A total of 66 participants who were on first line antituberculotic therapy consented for the study. Data was collected using a questionnaire and analysed using SPSS version 22.0. Results: about 77% (n=51) of the participants had experienced ADRs. Gastrointestinal symptoms were the most commonly reported symptoms of ADR (80%, n=41). Regarding adherence, over half (51.0%, n=26) said the occurrence of the Adverse Drug Reaction had affected the manner in which they take their medications. Of these, 84.6% (n=22) of the participants indicated that they skipped/missed their medications and 15.4% stopped the medication entirely. About 39.2% (n=20) reported ADRs to a healthcare practitioner and 60.8% did not. All the reported cases were managed by a health practitioner using another medication. Conclusion: the study showed that ADRs are common among patients receiving first line ATT. Gastrointestinal tract (GIT) related ADRs were the most common. Adherence to first line antitubercular therapy is poor as a result of adverse drugs reaction.


Assuntos
Antituberculosos/efeitos adversos , Adesão à Medicação/estatística & dados numéricos , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/administração & dosagem , Criança , Estudos Transversais , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Gana , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto Jovem
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