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1.
Artículo en Inglés | MEDLINE | ID: mdl-33799350

RESUMEN

Tuberculosis patients "resistant to isoniazid and susceptible to rifampicin (Hr-TB)" remain neglected, despite a high burden and poor outcomes. The World Health Organization (WHO) recommends a 6 month regimen consisting of levofloxacin, rifampicin, ethambutol, and pyrazinamide (LRZE) to treat Hr-TB. In contrast, Uzbekistan uses a 9 month regimen (LRZE plus a second-line injectable in the first 3 months). We aimed to assess the treatment outcomes of this novel regimen among Hr-TB patients treated in two regions of Uzbekistan (Fergana and Bukhara) in 2017-2018. We conducted a cohort study involving secondary analysis of routine surveillance data. Of 132 Hr-TB patients, 105 (80%) were successfully treated. Death was the predominant unsuccessful outcome (13, 10%) followed by "treatment failure" (10, 8%) and "lost to follow-up" (4, 2%). High treatment success is an indicator of the potential effectiveness of the novel regimen and adds to the limited global evidence on this issue. However, the sample size was small and there was no comparison group. Since the study was conducted in two regions of Uzbekistan only, the findings have limited generalizability. We recommend future research using an adequate sample size and an appropriate study design (randomized controlled trial or prospective cohort with a control group receiving the WHO-recommended regimen).


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Antituberculosos/uso terapéutico , Estudios de Cohortes , Humanos , Isoniazida/uso terapéutico , Estudios Prospectivos , Rifampin/uso terapéutico , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Uzbekistán/epidemiología
2.
BMJ Case Rep ; 14(4)2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33888483

RESUMEN

Osteoarticular tuberculosis of flat bones of the chest wall such as sternum, scapula and rib is extremely rare in children. Because of its atypical clinical presentation mimicking malignant bone tumours, diagnosis remains a challenge. Histological and microbiological diagnosis remains confirmatory. Antitubercular therapy is the cornerstone in management.


Asunto(s)
Neoplasias Óseas , Pared Torácica , Tuberculosis Osteoarticular , Antituberculosos/uso terapéutico , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/tratamiento farmacológico , Niño , Humanos , Esternón/diagnóstico por imagen , Tuberculosis Osteoarticular/diagnóstico , Tuberculosis Osteoarticular/tratamiento farmacológico
6.
BMC Infect Dis ; 21(1): 292, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33752637

RESUMEN

BACKGROUND: The World Health Organization (WHO) End TB strategy aims to reduce mortality due to tuberculosis (TB) to less than 5% by 2035. However, mortality due to multidrug-resistant tuberculosis (MDR-TB) remains particularly high. Globally, almost 20% of patients started on MDR-TB treatment die during the course of treatment every year. We set out to examine the risk factors for mortality among a cohort of patients diagnosed with MDR-TB in Uganda. METHODS: We conducted a case-control study nested within the national MDR-TB cohort. We defined cases as patients who died from any cause during the course of MDR-TB treatment. We selected two controls for each case from patients alive and on MDR-TB treatment at the time that the death occurred (incidence-density sampling). We matched the cases and controls on health facility at which they were receiving care. We performed conditional logistic regression to identify the risk factors for mortality. RESULTS: Data from 198 patients (66 cases and 132 controls) started on MDR-TB treatment from January 1 to December 31, 2016, was analyzed for this study. Cases were similar to controls in age/sex distribution, occupation and history of TB treatment. However, cases were more likely to be HIV infected while controls were more likely to have attained secondary level education. On multivariate regression analysis, co-infection with HIV (aOR 1.9, 95% CI [1.1-4.92] p = 0.05); non-adherence to MDR-TB treatment (aOR 1.92, 95% CI [1.02-4.83] p = 0.04); age over 50 years (aOR 3.04, 95% CI [1.13-8.20] p = 0.03); and having no education (aOR 3.61, 95% CI [1.1-10.4] p = 0.03) were associated with MDR-TB mortality. CONCLUSION: To mitigate MDR-TB mortality, attention must be paid to provision of social support particularly for older persons on MDR-TB treatment. In addition, interventions that support treatment adherence and promote early detection and management of TB among HIV infected persons should also be emphasized.


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Adolescente , Adulto , Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Niño , Preescolar , Coinfección/diagnóstico , Escolaridad , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Lactante , Recién Nacido , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Análisis de Supervivencia , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/mortalidad , Uganda/epidemiología , Adulto Joven
7.
Life Sci ; 274: 119301, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33675895

RESUMEN

Tuberculosis is one of the deadliest infectious diseases existing in the world since ancient times and still possesses serious threat across the globe. Each year the number of cases increases due to high drug resistance shown by Mycobacterium tuberculosis (Mtb). Available antimycobacterial drugs have been classified as First line, Second line and Third line antibiotics depending on the time of their discoveries and their effectiveness in the treatment. These antibiotics have a broad range of targets ranging from cell wall to metabolic processes and their non-judicious and uncontrolled usage in the treatment for years has created a significant problem called multi-drug resistant (MDR) tuberculosis. In this review, we have summarized the mechanism of action of all the classified antibiotics currently in use along with the resistance mechanisms acquired by Mtb. We have focused on the new drug candidates/repurposed drugs, and drug in combinations, which are in clinical trials for either treating the MDR tuberculosis more effectively or involved in reducing the time required for the chemotherapy of drug sensitive TB. This information is not discussed very adequately on a single platform. Additionally, we have discussed the recent technologies that are being used to discover novel resistance mechanisms acquired by Mtb and for exploring novel drugs. The story of intrinsic resistance mechanisms and evolution in Mtb is far from complete. Therefore, we have also discussed intrinsic resistance mechanisms of Mtb and their evolution with time, emphasizing the hope for the development of novel antimycobacterial drugs for effective therapy of tuberculosis.


Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Preparaciones Farmacéuticas/administración & dosificación , Preparaciones Farmacéuticas/clasificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Animales , Antituberculosos/clasificación , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
8.
Medicine (Baltimore) ; 100(9): e24376, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33655913

RESUMEN

INTRODUCTION: Total elbow arthroplasty (TEA) is an orthopedic procedure that is relatively infrequently performed, but its use has been increasing over time. Infection remains one of the most concerning complications after TEA, although Mycobacterium tuberculosis (TB) as a microbial etiology, is extremely rare. Here, we present a case of M. tuberculosis infection after TEA. PATIENT CONCERNS: A 45-year-old woman underwent TEA for severe traumatic arthritis of the elbow following failure of conservative treatment. Four months after TEA, the patient experienced progressive elbow pain and swelling, without other external signs of infection such as a sensation of local heating and erythematous alterations. DIAGNOSIS: Pulmonary computed tomography showed stable pulmonary TB in the right upper lobe. The T-SPOT, TB, and purified protein derivative test results were positive, and M. tuberculosis exhibited growth on cultures. The final diagnosis was periprosthetic infection of M. tuberculosis. INTERVENTIONS: The patient was treated with debridement with submission of deep tissue cultures. According to these cultures and suggestions of a bacteriologist, anti-TB treatment was administered for 12 months. OUTCOMES: The symptoms of the infection were controlled, and the prosthesis was retained. At the time of writing this case report, the elbow prosthesis had survived for more than 2 years, and no recurrent infection had been observed. CONCLUSION: The diagnosis of TB infection after TEA is difficult to confirm due to its nonspecific signs and symptoms. Despite the extremely low incidence, failure to consider this possibility for diagnosis can lead to delayed treatment. Proper diagnosis allows for antitubercular therapy with retention of a prosthesis.


Asunto(s)
Artroplastia de Reemplazo de Codo/efectos adversos , Articulación del Codo/microbiología , Prótesis de Codo/microbiología , Mycobacterium tuberculosis , Infecciones Relacionadas con Prótesis/microbiología , Tuberculosis Osteoarticular/microbiología , Antituberculosos/uso terapéutico , Desbridamiento , Articulación del Codo/cirugía , Femenino , Humanos , Persona de Mediana Edad , Tuberculosis Osteoarticular/terapia
9.
BMC Infect Dis ; 21(1): 254, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33691624

RESUMEN

BACKGROUND: The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity. METHODS: Patients with MDR-TB treated at our institution receive amikacin at 8-10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. RESULTS: Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6-24.8%); 22.2% had subjective hearing loss (95% CI 11.2-37.1%) and 31.9% subjective tinnitus (95% CI 19.1-47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8-38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84-99%). CONCLUSIONS: Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.


Asunto(s)
Amicacina/uso terapéutico , Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Amicacina/efectos adversos , Estudios de Cohortes , Monitoreo de Drogas , Femenino , Pérdida Auditiva/inducido químicamente , Humanos , Masculino , Estudios Retrospectivos , Acúfeno/inducido químicamente , Resultado del Tratamiento , Organización Mundial de la Salud
11.
Zhonghua Jie He He Hu Xi Za Zhi ; 44(3): 225-229, 2021 Mar 12.
Artículo en Chino | MEDLINE | ID: mdl-33721936

RESUMEN

Objective: To analyze the drug resistance of tuberculosis patients to clofazimine. Methods: Retrospective analysis was conducted on the case data of 1 770 tuberculosis patients in Department of tuberculosis, Beijing Chest Hospital affiliated to Capital Medical University from January 2015 to June 2018, including 1 225 males and 545 females, aged 8-92 (43.2±15.2) years old. Drug sensitivity tests using proportion method (hereinafter referred to as drug susceptibility test) for TB strains anti-tb drug resistance test. Using χ2 test or Fisher's exact test. Results: 1 770 cases of tuberculosis patients, 1 713 cases of patients with clofazimine sensitive, of 57 patients with drug resistance, and resistant rate was 3.2% (57/1 770), including patients with recurrent clofazimine, significantly higher than the initial percentages of patients [5.8% (38/656), 1.7% (19/1 114), χ²= 22.129, P = 0.000, P<0.01]; The drug resistance rates of poly-resistant, multi-drug resistant and extensively resistant patients to clofazimine were 1.0% (17/1 770), 1.2% (21/1 770) and 1.1% (19/1 770), respectively. Has a history of hospitalization of clofazimine resistance of multidrug-resistant and extensively drug-resistant patients resistant rate 2.4% (14/594), 2.7% (16/594), respectively, higher than 0.6% (7/1 176) with no history of hospitalized patients, 0.3% (3/1 176), the differences were statistically significant (χ²=10.447,22.099,P=0.001,<0.001). Conclusion: Clofazimine has a low resistance rate, which can improve the treatment success rate of patients with drug-resistant tuberculosis and has important value.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Niño , Clofazimina/farmacología , Clofazimina/uso terapéutico , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adulto Joven
12.
J Infect Public Health ; 14(4): 508-513, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33743373

RESUMEN

Mycobacterium tuberculosis, the bacterium that causes tuberculosis, has long been an unpleasant neighbour of humans. Following transmission of the bacterium from patients with active infection, new hosts do not immediately develop symptoms, as M. tuberculosis initially remains quiescent. However, it is eventually triggered, leading to the infection of other individuals. Humans are the exclusive host, and the rapid proliferation of the human population worldwide along with increasing globalisation have contributed to the pathogen's persistence, as have the survival strategies employed by M. tuberculosis, especially its resistance to several antimicrobials. Defeating this enemy will require novel approaches.


Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/tratamiento farmacológico , Antituberculosos/farmacología , Humanos , Mycobacterium tuberculosis/efectos de los fármacos
13.
Artículo en Inglés | MEDLINE | ID: mdl-33787739

RESUMEN

The emergence and spread of extensively drug-resistant tuberculosis (XDR-TB) is a serious threat to global health. Therefore, its rapid diagnosis is crucial. The present study aimed to characterize mutations conferring resistance to second line drugs (SLDs) within multidrug Mycobacterium tuberculosis (MDR-MTB) isolates and to estimate the occurrence of XDR-TB in Casablanca, Morocco. A panel of 200 MDR-TB isolates was collected at the Pasteur Institute between 2015-2018. Samples were subjected to drug susceptibility testing to Ofloxacin (OFX), Kanamycin (KAN) and Amikacin (AMK). The mutational status of gyrA, gyrB, rrs, tlyA and eis was assessed by sequencing these target genes. Drug susceptibility testing for SLDs showed that among the 200 MDR strains, 20% were resistant to OFX, 2.5% to KAN and 1.5% to AMK. Overall, 14.5% of MDR strains harbored mutations in gyrA, gyrB, rrs and tlyA genes. From the 40 OFXR isolates, 67.5% had mutations in QRDR of gyrA and gyrB genes, the most frequent one being Ala90Val in gyrA gene. Of note, none of the isolates harbored simultaneously mutations in gyrA and gyrB genes. In eight out of the 200 MDR-TB isolates resistant either to KAN or AMK, only 25% had A1401G or Lys89Glu change in rrs and tlyA genes respectively. This study is very informative and provides data on the alarming rate of fluoroquinolone resistance which warrants the need to implement appropriate drug regimens to prevent the emergence and spread of more severe forms of Mycobacterium tuberculosis drug resistance.


Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Técnicas de Genotipaje , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Marruecos/epidemiología , Mutación/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Análisis de Secuencia de ADN , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
14.
Artículo en Inglés | MEDLINE | ID: mdl-33787745

RESUMEN

Tuberculosis is a worldwide public health problem, which, even with available treatment, continues to cause deaths worldwide. One of the obstacles to control the disease is the multifactorial difficulty of patients to adhere to treatment, in addition to the difficulty of health workers in circumventing barriers to implement strategies such as the directly observed treatment (DOT). The aim of this study is to analyze the performance and challenges faced by health workers in the use of DOT in tuberculosis. This is a descriptive, quali-quantitative study using data from interviews with primary-care professionals working in nine municipalities of Parana State, Brazil. The professionals answered a questionnaire containing four closed questions about DOT and an open question related to their professional opinion about the strategy. Quantitative data were entered into a spreadsheet and statistically propagated. Qualitative data were treated from the transcription of statements, subsequently submitted to content analysis. Of the 387 professionals interviewed, at least 58.9% had some knowledge about DOT. Among the main challenges faced by the professionals are: lack of user commitment to treatment (48.3%), users' difficulty in attending the basic health clinics (BHC) (31.4%), professionals' difficulty to reach the place where patients are treated (8.8 %), insufficient staff / lack of human resources (4.1%) and use of illicit drugs by patients (3.9%). Blaming the user and the lack of resources are the main highlights, in addition to issues such as the professionals' lack of access and knowledge that are highlighted by the difficulty of patients to adhere to the treatment of tuberculosis according to the participants' statements. The issues were raised by health workers manifestations involving adherence to treatment according to the DOT in the studied health region. It is possible, in this context, to observe the need for improvement in the knowledge of professionals with regard to the DOT, the importance of their bond with patients and families and the recognition of the part of responsibility that belongs to the health team on guaranteeing treatment.


Asunto(s)
Antituberculosos/uso terapéutico , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Actitud del Personal de Salud , Brasil , Terapia por Observación Directa , Humanos , Entrevistas como Asunto , Cumplimiento de la Medicación , Persona de Mediana Edad , Aceptación de la Atención de Salud , Investigación Cualitativa , Tuberculosis/psicología , Adulto Joven
15.
BMC Infect Dis ; 21(1): 261, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33711936

RESUMEN

BACKGROUND: Tuberculosis is a devastating and a deadly disease despite the novel advances in its diagnostic tools and drug therapy. Drug resistant Mycobacterium contributes a great share to tuberculosis mortality. Status of drug resistance and patients' awareness toward the disease is unknown in northeastern Ethiopia. Thus, the aim of this study was to determine the phenotypic and genotypic drug sensitivity patterns and associated factors in Oromia Special Zone and Dessie Town, northeastern Ethiopia. METHODS: In a cross-sectional study, 384 smear positive tuberculosis cases were recruited and Löwenstein-Jensen culture was done. The performance of GenoTypic MTBDRplus assay using the conventional BACTEC MGIT 960 as a "gold standard" was determined. Drug resistant strains were identified using spoligotyping. Pearson Chi-square test was used to determine the association of drug sensitivity test and tuberculosis type, lineages, dominant strains and clustering of the isolates. RESULTS: The 384 smear positive Mycobacterium samples were cultured on LJ media of which 29.2% (112/384) as culture positive. A fair agreement was found between MTBDRplus assay and the conventional MGIT test in detecting the Mycobacterium tuberculosis with sensitivity, specificity, positive and negative predictive value of 94.2, 30.2, 68.4 and 76.5%, respectively. Among LJ culture positive samples 95 of them gave valid result for MTBDRplus assay and 16.8% (16/95) as drug resistant. Similarly, MGIT subculture was made for the 112 isolates and 69 of them gave positive result with 15.9% (11/69) as drug resistant. Cohen's kappa value showed almost a perfect agreement between the two testing methods in detecting rifampicin (sensitivity 100% and specificity 98.3%) and multi-drug resistance (sensitivity 83.3% and specificity 100%). Spoligotyping identified 76.5% (13/17) of the drug resistant isolates as Euro-American and family 33 as the predominant family. Significant association was observed between drug resistant isolates and the dominant strains (χ2: 34.861; p = 0.040) of the Mycobacterium. CONCLUSION: Higher magnitude of drug resistance was found in the study area. The GenoTypic MDRTBplus assay had an acceptable drug sensitivity testing performance.


Asunto(s)
Mycobacterium tuberculosis/genética , Tuberculosis/diagnóstico , Adolescente , Adulto , Anciano , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Estudios Transversales , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Etiopía , Femenino , Genotipo , Humanos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Fenotipo , Juego de Reactivos para Diagnóstico , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto Joven
17.
Georgian Med News ; (310): 93-101, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33658416

RESUMEN

The aim of the study was to assess general characteristics of drug resistant tuberculosis and its association with treatment outcomes in Georgia. A retrospective cohort study was conducted among 1581 DR-TB adult (18+) patients, from 2015 - 2020 cohorts, whose anti-tuberculosis treatment outcomes was known. Adjusted analysis of the study participants data [1581 (100%)] shows significant association of a successful TB treatment outcome with the "Female gender" (adjusted OR 1.78, 95% CI: 1.33 - 2.39, p<0.001), "New TB case" (adjusted OR 2.34, 95% CI: 1.88-2.91, p<0.001) and with "HIV negative status" (OR 2.33; 95% CI 1.53-3.55; p<0.001). Based on bivariate and multivariate analysis of the study data, the significant association of a treatment outcome with other key factors, including "New drugs in the regimen" was not found. Since the programmatic using of the new effective DR-TB regimens are widely recommended only from 2019, the treatment outcomes of all patients on these regimens are still not defined. Further studies are necessary to assess complete data of the patients on new DR-TB regimens and its association with the treatment outcomes.


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Adulto , Antituberculosos/uso terapéutico , Femenino , Georgia (República)/epidemiología , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
18.
Medicine (Baltimore) ; 100(8): e24569, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663064

RESUMEN

RATIONALE: Lung cancer and pulmonary infections can have similar clinical and radiographic manifestations. Treatment for the coexistence of epidermal growth factor receptor (EGFR)-mutant pulmonary adenocarcinoma and tuberculosis remains unclear. PATIENT CONCERNS: We reported a case of EGFR-mutant lung adenocarcinoma (mimicking pulmonary infections) that coexisted with pulmonary tuberculosis during the course of the disease. DIAGNOSES: The patient was initially diagnosed with pneumonia-like pulmonary adenocarcinoma with EGFR exon 19 deletions based on computed tomography scan, fiberoptic bronchoscopy, pathology, and genetic analysis, and then coexistence with active tuberculosis (TB) was confirmed via laboratory examinations and TB-DNA polymerase chain reaction. INTERVENTIONS: Antibiotics and gefitinib were administered initially. A combination of gefitinib and anti-TB treatment was then administered when active TB was confirmed, and osimertinib was then prescribed because the disease was progressive and EGFR T790 M mutation was detected. OUTCOMES: The patient has survived with a stable disease status to date. LESSONS: Exploring and ruling out differential diagnoses between pulmonary malignancies and infectious diseases is vital for treatment decisions and outcomes. The combined gefitinib-anti-TB regimen was safe, though it needed modification.


Asunto(s)
Adenocarcinoma del Pulmón/complicaciones , Receptores ErbB/genética , Neoplasias Pulmonares/complicaciones , Tuberculosis Pulmonar/complicaciones , Acrilamidas/uso terapéutico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Anciano , Compuestos de Anilina/uso terapéutico , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Antituberculosos/uso terapéutico , Femenino , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Tuberculosis Pulmonar/tratamiento farmacológico
19.
Nat Commun ; 12(1): 1141, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602926

RESUMEN

The composition of the gastrointestinal microbiota influences systemic immune responses, but how this affects infectious disease pathogenesis and antibiotic therapy outcome is poorly understood. This question is rarely examined in humans due to the difficulty in dissociating the immunologic effects of antibiotic-induced pathogen clearance and microbiome alteration. Here, we analyze data from two longitudinal studies of tuberculosis (TB) therapy (35 and 20 individuals) and a cross sectional study from 55 healthy controls, in which we collected fecal samples (for microbiome analysis), sputum (for determination of Mycobacterium tuberculosis (Mtb) bacterial load), and peripheral blood (for transcriptomic analysis). We decouple microbiome effects from pathogen sterilization by comparing standard TB therapy with an experimental TB treatment that did not reduce Mtb bacterial load. Random forest regression to the microbiome-transcriptome-sputum data from the two longitudinal datasets reveals that renormalization of the TB inflammatory state is associated with Mtb pathogen clearance, increased abundance of Clusters IV and XIVa Clostridia, and decreased abundance of Bacilli and Proteobacteria. We find similar associations when applying machine learning to peripheral gene expression and microbiota profiling in the independent cohort of healthy individuals. Our findings indicate that antibiotic-induced reduction in pathogen burden and changes in the microbiome are independently associated with treatment-induced changes of the inflammatory response of active TB, and the response to antibiotic therapy may be a combined effect of pathogen killing and microbiome driven immunomodulation.


Asunto(s)
Microbioma Gastrointestinal , Inflamación/microbiología , Inflamación/patología , Tuberculosis/complicaciones , Tuberculosis/microbiología , Adulto , Algoritmos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Carga Bacteriana/efectos de los fármacos , Biodiversidad , Estudios de Casos y Controles , Estudios de Cohortes , Microbioma Gastrointestinal/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/complicaciones , Modelos Biológicos , Reproducibilidad de los Resultados , Tuberculosis/tratamiento farmacológico , Tuberculosis/patología
20.
J Infect ; 82(3): 371-377, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33556430

RESUMEN

The drug resistance prevalence data facilitates selection of the initial drug for treating multidrug-resistant tuberculosis (MDR-TB). The aim of this study was to investigate the prevalence and molecular characterization of seven additional types of drug resistances among MDR-TB isolates collected from the first/only nationwide drug resistance surveillance in China. A total of 391 out of the 401 MDR-TB strains were successfully recovered by Löwenstein-Jensen medium. Drug susceptibility testing was performed against moxifloxacin (Mfx), bedaquiline (Bdq), linezolid (Lzd), clofazimine (Cfz), cycloserine (Cs), delamanid (Dlm) and pyrazinamide (PZA). The strains were subjected to whole-genome sequencing for the analysis corresponding drug resistant genes and their profiles. 269 (68.80%) were simple MDR-TB, 28 (7.16%) were extensively drug-resistant tuberculosis (XDR-TB) and 94 (24.04%) were pre-XDR-TB. Dlm, Lzd, Cfz and Bdq presented the lowest drug resistant rates i.e. 3.32% (13/391), 3.84% (15/391),6.65% (26/391) and 7.16% (28/391), respectively. Mfx (17.39%, 68/391) and CS (13.55%, 53/391) also demonstrated strong potencies against the MDR strains, whereas PZA (38.36%, 150/391) presented much higher resistant rate. 54.41% (37/68) Mfx-resistant strains carried mutations located within gyrA or gyrB. 70.15% (94/134) PZA-resistant strains had pncA mutations. Two of the 26 Cfz-resistant isolates had mutation in Rv0678 were also resistant to Bdq. Dlm, Lzd, Cfz and Bdq exhibited excellent activity against MDR-TB, including XDR-TB. These data highlighted the necessity of a timely, feasible and reliable DST, while genotypic DST for Mfx and PZA is promising at this moment.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , China/epidemiología , Resistencia a Medicamentos , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/genética , Prevalencia , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
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