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1.
BMC Infect Dis ; 20(1): 446, 2020 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-32576154

RESUMEN

BACKGROUND: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea. METHODS: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15-34 years), middle (35-59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed. RESULTS: Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups. CONCLUSIONS: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.


Asunto(s)
Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Fluoroquinolonas/uso terapéutico , Isoniazida/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
2.
Medicine (Baltimore) ; 99(22): e20375, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32481422

RESUMEN

INTRODUCTION: The prevalence of diabetes continues to rise around the world. Diabetic foot is a serious complication of diabetes, and diabetic patients with diabetic foot osteomyelitis (DFO) have a fourfold increased risk of amputation, usually indicating death. Therefore, it is particularly important to seek a more effective treatment for DFO. The treatment of DFO varies from person to person, and antimicrobial therapies vary widely. A large number of clinical studies have shown that rifampicin adjuvant therapy can reduce the rate of amputation and mortality in DFO patients. However, there is no systematic summary of clinical evidence, which limits the clinical application of rifampicin. Therefore, we attempted to provide high-quality evidence for the clinical efficacy and safety of rifampin in the adjuvant treatment of DFO through this meta-analysis. METHODS: English literature is mainly searched in Cochrane Library, PubMed, EMBASE and Web of Science, while Chinese literature is from CNKI, CBM, VIP and Wangfang databases. At the same time, we will search clinical registration tests and gray literature. Two methodologically trained researchers will read the title, abstract, and full text, and independently select qualified literature based on inclusion and exclusion criteria. Binary data is expressed as relative risk, continuous data is expressed as mean difference or standard mean difference. The final data are synthesized using a fixed effect model or a random effect model, depending on the presence of heterogeneity. In the end, the patient's amputation rate and mortality were the main research indicators. Survival rate, HbA1c, serum creatinine, changes in ulcer area, and SF-36 quality of life assessment were used as secondary indicators. We will perform a sensitivity analysis to assess the stability of the results. Then the publication bias was evaluated by funnel plot analysis and Egger test. Finally, we will use a "recommendation grading, evaluation, formulation and evaluation" system to assess the quality of the evidence. All data analysis will be meta-analyzed by the statistical software RevMan software version 5.3. RESULTS: This study will provide a high-quality comprehensive report on the effectiveness and safety of rifampicin in the treatment of DFO, and our findings will be published in peer-reviewed journals. CONCLUSION: This systematic review and meta-analysis will provide a comprehensive summary and careful evaluation of rifampicin as an adjuvant treatment of DFO with a view to providing multiple options for clinical treatment of the disease. REGISTRATION NUMBER:: is INPLASY202040084.


Asunto(s)
Antibacterianos/uso terapéutico , Pie Diabético/tratamiento farmacológico , Osteomielitis/tratamiento farmacológico , Rifampin/uso terapéutico , Adyuvantes Farmacéuticos/uso terapéutico , Pie Diabético/complicaciones , Humanos , Osteomielitis/etiología
3.
PLoS One ; 15(4): e0230848, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32353043

RESUMEN

BACKGROUND: Zimbabwe is one of the thirty countries globally with a high burden of multidrug-resistant tuberculosis (TB) or rifampicin-resistant TB (MDR/RR-TB). Since 2010, patients diagnosed with MDR/RR-TB are being treated with 20-24 months of standardized second-line drugs (SLDs). The profile, management and factors associated with unfavourable treatment outcomes of MDR/RR TB have not been systematically evaluated in Zimbabwe. OBJECTIVE: To assess treatment outcomes and factors associated with unfavourable outcomes among MDR/RR-TB patients registered and treated under the National Tuberculosis Programme in all the district hospitals and urban healthcare facilities in Zimbabwe between January 2010 and December 2015. METHODS: A cohort study using routinely collected programme data. The 'death', 'loss to follow-up' (LTFU), 'failure' and 'not evaluated' were considered as "unfavourable outcome". A generalized linear model with a log-link and binomial distribution or a Poisson distribution with robust error variances were used to assess factors associated with "unfavourable outcome". The unadjusted and adjusted relative risks were calculated as a measure of association. A 𝑝value< 0.05 was considered statistically significant. RESULTS: Of the 473 patients in the study, the median age was 34 years [interquartile range, 29-42] and 230 (49%) were males. There were 352 (74%) patients co-infected with HIV, of whom 321 (91%) were on antiretroviral therapy (ART). Severe adverse events (SAEs) were recorded in 118 (25%) patients; mostly hearing impairments (70%) and psychosis (11%). Overall, 184 (39%) patients had 'unfavourable' treatment outcomes [125 (26%) were deaths, 39 (8%) were lost to follow-up, 4 (<1%) were failures and 16 (3%) not evaluated]. Being co-infected with HIV but not on ART [adjusted relative risk (aRR) = 2.60; 95% CI: 1.33-5.09] was independently associated with unfavourable treatment outcomes. CONCLUSION: The high unfavourable treatment outcomes among MDR/RR-TB patients on standardized SLDs were coupled with a high occurrence of SAEs in this predominantly HIV co-infected cohort. Switching to individualized all oral shorter treatment regimens should be considered to limit SAEs and improve treatment outcomes. Improving the ART uptake and timeliness of ART initiation can reduce unfavourable outcomes.


Asunto(s)
Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Zimbabwe
4.
BMC Infect Dis ; 20(1): 315, 2020 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-32345228

RESUMEN

BACKGROUND: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. METHODS: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. RESULTS: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3-8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0218). CONCLUSION: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.


Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Índice de Masa Corporal , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Estudios de Cohortes , Depresión/etiología , Disnea/etiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adulto Joven
5.
An Bras Dermatol ; 95(3): 343-346, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32303434

RESUMEN

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment.


Asunto(s)
Artritis Reactiva/inmunología , Inmunocompetencia , Huésped Inmunocomprometido , Tuberculosis Cutánea/inmunología , Tuberculosis Cutánea/patología , Antituberculosos/uso terapéutico , Etambutol/uso terapéutico , Humanos , Isoniazida/uso terapéutico , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Úlcera Cutánea/tratamiento farmacológico , Úlcera Cutánea/inmunología , Úlcera Cutánea/patología , Resultado del Tratamiento , Tuberculosis Cutánea/tratamiento farmacológico , Adulto Joven
6.
J Bras Pneumol ; 46(2): e20200009, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-32215450

RESUMEN

Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.


Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Protocolos Clínicos , Ensayos Clínicos como Asunto , Clofazimina/uso terapéutico , Humanos , Linezolid/uso terapéutico , Rifampin/uso terapéutico
7.
PLoS One ; 15(3): e0229995, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32150595

RESUMEN

BACKGROUND: Global roll out of Xpert MTB/RIF technology has resulted in dramatic changes in TB diagnosis. However, benefits in resource-limited, high-burden TB/HIV settings, remain to be verified. In this paper we describe the characteristics of a large cohort of TB patients in a rural hospital in Southern Mozambique before and after Xpert MTB/RIF introduction, together with some determinants of favorable treatment outcome. METHODS: We conducted a retrospective cohort study of TB infected patients ≥15 years of age, diagnosed and treated at Carmelo Hospital of Chókwè between January 1, 2006 and December 31, 2017. Patient demographic and clinical characteristics, and treatment outcomes were recorded and compared before and after Xpert MTB/RIF, which was introduced in the second semester of 2012. RESULTS: 9,655 patients were analyzed, with 44.1% females. HIV testing was conducted in 99.9% of patients, with 82.8% having TB/HIV co-infection. 73.2% of patients had a favorable treatment outcome. No increase was observed in the number of TB patients identified after introduction of Xpert MTB/RIF testing. CONCLUSION: Upon introduction, Xpert testing seemed to have a punctual beneficial effect on TB treatment outcomes, however this effect apparently disappeared shortly afterwards. Challenges remain for integration of TB and HIV care, as worse outcomes are reported for those patients diagnosed with TB shortly after starting ART, and also for those never starting ART. The need of reasonably excluding TB disease before ART start should be highlighted to every health care provider engaged in HIV care.


Asunto(s)
Infecciones por VIH/complicaciones , Rifampin/farmacología , Población Rural/estadística & datos numéricos , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mozambique , Estudios Retrospectivos , Rifampin/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento , Tuberculosis/complicaciones , Adulto Joven
9.
PLoS One ; 15(3): e0230383, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32191760

RESUMEN

BACKGROUND: Staphylococcus aureus (S. aureus) bacteremia (SAB) has high morbidity and mortality, with the development of methicillin-resistant S. aureus (MRSA) and the recognized shortcomings of vancomycin, its management is becoming more complicated. Considering the capability to penetrate cells, tissues and biofilms, rifampin has been used as adjunctive agent to against staphylococcal activity. OBJECTIVES: We performed this meta-analysis, aimed to explore the efficacy of adjunctive rifampin for the treatment of SAB. METHODS: Medical literatures were searched in the Pubmed, Medline, Embase and Cochrane databases up to October 2018. Patients with SAB received treatment with or without rifampin were included. The risk ratio (RR) and 95% confidence intervals (CI) of mortality, rate of bacteriological failure and relapse were estimated. RESULTS: Seven articles (five randomized controlled trials and two retrospective cohort studies) enrolling 979 and 636 patients of SAB treated with and without rifampin, respectively, were included. There was no difference of mortality between the adjunctive rifampin therapy and standard therapy on SAB (RR: 0.771, 95% CI: 0.442 to 1.347, I2 = 70.4%). In the subgroup analyses, the decreased mortality was observed in the adjunctive rifampin treatment for patients without MRSA infection (RR: 0.509, 95% CI: 0.372 to 0.697, I2 = 8.8%). In addition, there was no difference of the rate of bacteriologic failure (RR: 0.602, 95% CI: 0.198 to 1.825, I2 = 0.0%) or relapse (RR: 0.574, 95% CI: 0.106 to 3.112, I2 = 77.9%) between the adjunctive rifampin therapy and standard therapy on SAB. CONCLUSIONS: In general, insufficient evidence supported the efficacy of adjunctive use of rifampin for treatment of SAB, adding rifampin to standard therapy didn't decrease the incidence of death, rate of bacteriologic failure and relapse.


Asunto(s)
Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Rifampin/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/fisiología , Bacteriemia/mortalidad , Humanos , Sesgo de Publicación , Ensayos Clínicos Controlados Aleatorios como Asunto , Rifampin/farmacología , Riesgo , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/efectos de los fármacos , Resultado del Tratamiento
10.
Int J Infect Dis ; 92S: S37-S40, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32114201

RESUMEN

China is one of the countries with a high burden of tuberculosis (TB) and latent tuberculosis infection (LTBI). It was recently estimated that China had the highest LTBI burden in the world, with approximately 350 million persons living with the infection. The prevalence of LTBI in China is overestimated by tuberculin skin test (TST) as compared to interferon-gamma release assay (IGRA). A population-based study found that IGRA positivity rates ranged between 13.5% and 19.8%. The annual TB infection rate in the rural population was 1.5% based on persistent positive IGRA results in converters. The development of active TB from LTBI in the general rural population was 0.87 per 100 person-years in the first 2 years among individuals who newly converted to IGRA-positive. TB control in students has been paid more attention by the government, which also improved LTBI management among students in close contact with active TB patients. A 3-month regimen of twice-weekly rifapentine plus isoniazid (3H2P2, both with a maximum dose of 600 mg) has been practiced for LTBI treatment in China for years. With respect to LTBI management in populations using immune inhibitors, an expert consensus on TB prevention and management in tumor necrosis factor antagonist application was published in 2013 in China. In order to achieve the global goals of the End TB Strategy, China needs innovative ideas and technologies to reduce the TB incidence by management of LTBI, such as the identification of populations for LTBI testing and treatment, selecting and developing reliable LTBI tests, exploring safe and effective preventive treatment tools, and establishing a set of optimized LTBI management systems.


Asunto(s)
Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Antituberculosos/uso terapéutico , China/epidemiología , Humanos , Incidencia , Ensayos de Liberación de Interferón gamma , Isoniazida/uso terapéutico , Tuberculosis Latente/diagnóstico , Prevalencia , Rifampin/análogos & derivados , Rifampin/uso terapéutico , Población Rural , Prueba de Tuberculina , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
11.
Int J Infect Dis ; 92S: S72-S77, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32171953

RESUMEN

OBJECTIVE: To estimate the cost of a screening program for identifying latent tuberculosis (TB) infections in migrants to Oman. METHODS: A Markov model was used to estimate the cost of screening using an interferon-gamma release assay (IGRA) applied to all migrants from high TB endemic countries, followed by preventive TB treatment. RESULTS: The model compared seven different scenarios, with a comparison of the direct cost and the quality-adjusted life-years (QALYs) saved. CONCLUSIONS: IGRA testing followed by 3 months of preventive treatment with rifapentine/isoniazid (3HP) was the most cost-effective intervention.


Asunto(s)
Ensayos de Liberación de Interferón gamma/economía , Tuberculosis Latente/diagnóstico , Migrantes , Análisis Costo-Beneficio , Femenino , Humanos , Isoniazida/uso terapéutico , Tuberculosis Latente/economía , Cadenas de Markov , Tamizaje Masivo , Omán , Años de Vida Ajustados por Calidad de Vida , Rifampin/análogos & derivados , Rifampin/uso terapéutico , Tuberculosis/prevención & control
12.
PLoS One ; 15(3): e0230808, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32218585

RESUMEN

There is increasing interest in future, highly-potent 'pan-TB' regimens against tuberculosis (TB), that may be equally effective in both drug-susceptible and rifampicin-resistant (RR) forms of TB. Taking the example of India, the country with the world's largest burden of TB, we show that adoption of these regimens could be: (i) epidemiologically impactful, and (ii) cost-saving to the national TB programme, even if the regimen itself is more costly than current TB treatment. Mathematical modelling suggests that deployment of a pan-TB regimen in 2022 would reduce the annual incidence of TB in 2030 by 23.9% [95% Bayesian credible intervals [CrI] 17.6-30.8%] if used to treat all TB cases, and by 2.30% [95% CrI 1.57-3.48%] if used to treat only RR-TB. Notably, with a regimen costing less than USD 359 (95% CrI 287-441), treating all diagnosed TB cases with the pan-TB regimen yielded greater cost-savings than treating just those diagnosed with RR-TB. One limitation of our approach is that it does not capture the risk of resistance to the new regimen. We discuss ways in which this risk could be mitigated using modern adherence support mechanisms, as well as drug sensitivity testing at the point of TB diagnosis, to prevent new resistant forms from becoming established. A combination of such approaches would be important for maximising the useful lifetime of any future regimen.


Asunto(s)
Antituberculosos/uso terapéutico , Descubrimiento de Drogas , Modelos Estadísticos , Tuberculosis/tratamiento farmacológico , Humanos , India , Rifampin/uso terapéutico
15.
BMC Infect Dis ; 20(1): 202, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-32143583

RESUMEN

BACKGROUND: Brucellosis is a zoonotic infection transmitted from infected animals to humans, osteonecrosis of the femoral head (ONFH) is a devastating disease that affects patients' life with pain, dysfunction of walking and always lead to total hip arthroplasty (THA). We presented a case of ONFH which was very likely due to the infection of Brucella spp. CASE PRESENTATION: The patient was a 49 years-old male who was a herder living in Inner Mongolia, the northern part of China. He first showed recurrent fever then presented bilateral hip pain, which was confirmed to be brucellosis and ONFH on the right side of the hip. He was admitted to our center showed bilateral ONFH with the restrictive movement of both hips. We performed THA after it was confirmed that the infection has been cured. The patient can walk with the help of the walker the second day after surgery. CONCLUSION: Brucellosis is still a common epidemic disease worldwide, which can lead to many complications, brucellosis arthritis is the most common complication of Brucellosis. Osteonecrosis of the femoral head can also present in the patients with brucellosis. All the patients presented with recurrent fever and hip pain, who is from the epidemic region, should be taken both septic arthritis and ONFH into consideration.


Asunto(s)
Brucelosis/diagnóstico , Necrosis de la Cabeza Femoral/diagnóstico , Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Cadera , Brucelosis/complicaciones , Brucelosis/tratamiento farmacológico , China , Doxiciclina/uso terapéutico , Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Rifampin/uso terapéutico
16.
Med Sci Monit ; 26: e920350, 2020 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-32145061

RESUMEN

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.


Asunto(s)
Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Adulto , Antituberculosos/uso terapéutico , Femenino , Humanos , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Masculino , Persona de Mediana Edad , Pirazinamida/efectos adversos , Pirazinamida/uso terapéutico , Estudios Retrospectivos , Rifampin/efectos adversos , Rifampin/uso terapéutico , Factores de Riesgo , Tuberculosis/tratamiento farmacológico , Adulto Joven
17.
BMC Infect Dis ; 20(1): 87, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32000702

RESUMEN

BACKGROUND: Xpert® MTB/RIF assay is currently used in Ethiopia for the rapid diagnosis of Mycobacterium tuberculosis (MTB) and mutations that confer Rifampicin resistance. Rifampicin resistance is determined based on any mutation in the 81 bp of rpoB gene using five overlapping probes represented as Probe A (codons 507-511), Probe B (codons 512-518), Probe C (codons 518-523), Probe D (codons 523-529) and Probe E (codons 529-533). In this review, we assessed the frequency of missed probe types for Rifampicin Resistance results. METHODS: Data were reviewed from specimens received and tested using Xpert® MTB/RIF assay at Ethiopian National Tuberculosis Reference Laboratory, in Addis Ababa from 15 July 2016 to 31 December 2018 retrospectively. All archived data were reviewed carefully to describe missed probe types and the quantity of DNA in the sample. RESULTS: A total of 100 specimens were reported as MTB Detected Rifampicin Resistance Detected by Xpert® MTB/RIF assay. More than half (55%) of these results were reported from male patients. The median age was 28.0 years (5 months to 88 years). Majorities (62%) of the cases were detected from sputum. Among the total of 38 extrapulmonary samples, lymph node aspirates were accounted for 50% (19/38). The most common mutations (81.0%) were found in the Probe E region followed by Probe D (10.0%), and Probe B (3.0%). Mutations in Probe A and Probe C regions were not observed. However, six (6.0%) Rifampicin resistance cases were found without any missed probe type. The delta Ct max is ≥4.3. No specimen yielded Rifampicin resistance associated with more than one probe failure or mutation combinations. CONCLUSION: Mutations associated with Probe E (codons 529-533) region were identified as the commonest rpoB gene mutations. The Rifampicin resistance results found without any identified missing probe needs further study. The lower DNA amount was observed in extrapulmonary specimens compared with sputum.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Pruebas Genéticas/métodos , Mutación , Mycobacterium tuberculosis/genética , Rifampin/uso terapéutico , Tuberculosis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Codón/genética , ADN/análisis , Etiopía , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rifampin/efectos adversos , Sensibilidad y Especificidad , Esputo/microbiología , Tuberculosis/microbiología , Adulto Joven
18.
Science ; 367(6474): 200-204, 2020 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-31919223

RESUMEN

Drug combinations are widely used in clinical practice to prevent the evolution of resistance. However, little is known about the effect of tolerance, a different mode of survival, on the efficacy of drug combinations for preventing the evolution of resistance. In this work, we monitored Staphylococcus aureus strains evolving in patients under treatment. We detected the rapid emergence of tolerance mutations, followed by the emergence of resistance, despite the combination treatment. Evolution experiments on the clinical strains in vitro revealed a new way by which tolerance promotes the evolution of resistance under combination treatments. Further experiments under different antibiotic classes reveal the generality of the effect. We conclude that tolerance is an important factor to consider in designing combination treatments that prevent the evolution of resistance.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Microbiana/genética , Evolución Molecular , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/microbiología , Antibacterianos/uso terapéutico , ARN Polimerasas Dirigidas por ADN/genética , Daptomicina/farmacología , Daptomicina/uso terapéutico , Quimioterapia Combinada , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Polimorfismo de Nucleótido Simple , Rifampin/farmacología , Rifampin/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/farmacología , Vancomicina/uso terapéutico
19.
BMC Infect Dis ; 20(1): 19, 2020 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-31910878

RESUMEN

BACKGROUND: Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations. METHODS: MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression. RESULTS: Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34-0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified. CONCLUSIONS: Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability .


Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Pirazinamida/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adulto , Factores de Edad , Amidohidrolasas/genética , Antituberculosos/efectos adversos , Secuencia de Bases/genética , China/epidemiología , Diarilquinolinas/uso terapéutico , Genes Bacterianos/genética , Genotipo , Humanos , Linezolid/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Mutación Puntual/genética , Polimorfismo de Nucleótido Simple/genética , Prevalencia , Pirazinamida/efectos adversos , Rifampin/efectos adversos , Rifampin/uso terapéutico , Factores de Riesgo , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico
20.
BMC Public Health ; 20(1): 76, 2020 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-31952494

RESUMEN

BACKGROUND: Patient-centered care is pillar 1 of the "End TB" strategy, but little has been documented in the literature about what this means for people living with rifampicin-resistant (RR-TB). Optimizing care for such individuals requires a better understanding of the challenges they face and the support they need. METHODS: A qualitative study was done among persons living with RR-TB and members of their support network. A purposive sample was selected from a larger study population and open-ended interviews were conducted using a semi-standard interview guide. Interviews were recorded and transcribed and the content analyzed using an iterative thematic analysis based in grounded theory. RESULTS: 16 participants were interviewed from three different provinces. Four distinct periods in which support was needed were identified: 1) pre-diagnosis; 2) pre-treatment; 3) treatment; and 4) post-treatment. Challenges common in all four periods included: socioeconomic issues, centralized care, and the need for better counseling at multiple levels. CONCLUSIONS: Beyond being a "very humiliating illness", RR-TB robs people of their physical, social, economic, psychological, and emotional well-being far beyond the period when treatment is being administered. Efforts to tackle these issues are as important as new drugs and diagnostics in the fight against TB.


Asunto(s)
Actitud Frente a la Salud , Tuberculosis Resistente a Múltiples Medicamentos/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Dirigida al Paciente , Investigación Cualitativa , Rifampin/uso terapéutico , Sudáfrica , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto Joven
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