Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis.

Rationale: Current recommendations for the treatment of rifampicin- and multidrug-resistant tuberculosis include bedaquiline (BDQ) used for 6 months or longer. Evidence is needed to inform the optimal duration of BDQ. Objectives: We emulated a target trial to estimate the effect of three BDQ duration treatment strategies (6, 7-11, and ⩾12 mo) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis. Methods: To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse probability weighting. Measurements and Main Results: The 1,468 eligible individuals received a median of 4 (interquartile range, 4-5) likely effective drugs. In 87.1% and 77.7% of participants, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment was 0.85 (95% confidence interval [CI], 0.81-0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73-0.81) for 7-11 months, and 0.86 (95% CI, 0.83-0.88) for ⩾12 months. Compared with 6 months of BDQ, the ratio of treatment success was 0.91 (95% CI, 0.85-0.96) for 7-11 months and 1.01 (95% CI, 0.96-1.06) for ⩾12 months. Naive analyses that did not account for bias revealed a higher probability of successful treatment with ⩾12 months (ratio, 1.09 [95% CI, 1.05-1.14]). Conclusions: BDQ use beyond 6 months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time bias can influence estimates of the effects of treatment duration. Future analyses should explore the effect of treatment duration of BDQ and other drugs in subgroups with advanced disease and/or receiving less potent regimens.

Causas de hemoptisis en pacientes hospitalizados / Causes of hemoptysis in hospitalized patients

Objetivo. Determinar la variación a través del tiempo, de las causas de hemoptisis en pacientes hospitalizados. Material y Métodos. Estudio retrospectivo y transversal. Se revisó 251 historias clínicas de pacientes que fueron hospitalizados en el Hospital Dos de Mayo de Lima con diagnóstico de hemoptisis durante el período 2000-2011. Se recolectó variables como edad, sexo, procedencia, historia de tabaquismo, ocupación, antecedente de tuberculosis, entre otras. resultadOs. Las principales causas de hemoptisis fueron: tuberculosis activa (41,43 %), bronquiectasias (29,89%), cáncer pulmonar (7,97 %), micosis pulmonar (5,18 %), criptogénicas (4,38 %), bronquitis crónica (3,59 %), hidatidosis pulmonar (2,39 %) y neumonía (1,59 %). Se observó un incremento moderado en los casos de bronquiectasias y cáncer pulmonar en relación a los hallazgos reportados en el año 2000. Conclusión. Tuberculosis y bronquiectasias continúan liderando las principales causas de hemoptisis. Sin embargo, la proporción de tuberculosis como causa de hemoptisis ha disminuido en los últimos doce años y, a la vez, un incremento moderado de los casos de bronquiectasia y cáncer pulmonar.

Objective. To determine the over time variation of the causes of hemoptysis in hospitalized patients. Material and Methods. A retrospective and cross-sectional study was done. Two hundred and one medical histories of patients who were hospitalized in the Hospital Dos de Mayo of Lima with a diagnosis of hemoptysis during the period 2000-2011 was reviewed. Variables such as age, sex, origin, smoking habit, occupation, past history of tuberculosis, among others, were collected. results. The main causes of hemoptysis were: active TB (41,43 %), bronchiectasis (29,89 %), lung cancer (7,97 %), pulmonary mycosis (5,18 %), cryptogenic (4,38 %), chronic bronchitis (3,59 %), pulmonary hydatidosis (2,39 %) and pneumonia (1,59 %). It was observed a moderate increase in the cases of bronchiectasis and lung cancer in relation to the findings reported in the year 2000. Conclusin. Tuberculosis and bronchiectasis continue to lead the main causes of hemoptysis. However, the proportion of tuberculosis as a cause of hemoptysis has decreased in the last twelveyears and, at the same time, a moderate increase of cases of bronchiectasis and lung cancer is observed.

Tumor carcinoide pulmonar típico / Typical lung carcinoid tumor

Mujer de 42 años de edad, con tres años de enfermedad caracterizada por episodios de tos productiva, fiebre y disnea, tratada con antibióticos por infecciones bronquiales recurrentes que coincidían con episodios de rubor facial, diarreas acuosas, de una a dos veces por mes, de carácter autolimitado. Presentó episodios de hemoptisis leve. Pese a tener frotis negativo para M. tuberculosis, recibió tratamiento por supuesta tuberculosis pleural, en un centro de salud, sin mejoría clínica, por lo que fue hospitalizada. La radiografía de tórax mostró atelectasia del lóbulo medio e inferior derecho. La tomografía evidenció neoproliferación hilio-basal derecha con marcada captación de medio de contraste, linfonodos metastásicos en hilio y mediastino derecho, incluidos los del grupo subcarinal, con atelectasia crónica en lóbulo medio con bronquiectasias cilíndricas. En la primera broncoscopias, en el bronquio intermediario derecho, se observó unalesión polipoide avascularizada, redondeada, cubierta por membrana blanquecina que ocluía el 100% de la luz, muy friable, que sangraba al roce del cepillo. El Papanicolaou del aspirado bronquial reveló citología sugestiva de neoplasia maligna. En la segunda broncoscopia con biopsia, se demostró tumor carcinoide típico, con inmunohistoquímica positiva para panqueratina y cromogranina.

A 42 year-old female with 3-year disease characterized by episodes of productive cough, fever and dyspnea. She was treated with antibiotics for recurrent respiratory infections, coincident with episodes of facial flushing and watery and self-limited diarrhea which occurred 1-2 times monthly. She had mild bouts of hemoptysis. Despite negative smears for M. tuberculosis, she received 4-drug treatment for pleural tuberculosis, in a primary health center, without clinical improvement, so she was hospitalized. X-ray chest film showed atelectasis of right middle and lower lobe. Computed tomography showed right hilum neoproliferation with marked uptake of contrast, hilar and mediastinal lymph node metastasis including subcarinal group, with middle lobe atelectasis and chronic cylindrical bronchiectasis. A first bronchoscopy revealed, in the right intermediate bronchus, an avascularizaded, polypoid lesion, rounded, covered with a white membrane occluding 100% of bronchus lumen, very friable and bleeding to the brush touch, whose Papanicolaou smear revealed a cytology suggestive of malignancy. The second bronchoscopy and biopsy showed a typical carcinoid tumor with positive immunohistochemistry for panqueratine and chromogranin.

Síndrome DRESS inducido por fármacos antituberculosos en un paciente con diabetes mellitus tipo 2 / Antituberculous drugs-induced DRESS syndrome in a patient with type 2 diabetes mellitus

Presentamos el caso de un paciente varón de 48 años de edad, con diagnóstico de diabetes mellitus tipo 2, no controlada, de diez años de evolución, a quien se le diagnosticó tuberculosis pulmonar mediante signos clínicos, radiográficos y cultivo en esputo positivo para Mycobacterium tuberculosis, sensible a drogas antituberculosas de primera línea. Recibió isoniacida, rifampicina, etambutol y pirazinamida. Dos meses después de iniciado el tratamiento presentó hipersensibilidad a medicamentos, con los siguientes signos y síntomas: rash dérmico generalizado, prurito generalizado, anemia Coombs positiva, eosinofilia y síntomas sistémicos, compatibles con el síndrome DRESS (drug rash with eosinophilia and systemic symptoms). Ante ello, se suspendió la medicación antituberculosa y se instaló tratamiento con antihistamínicos y corticoides sistémicos, con remisión y mejoría de síntomas. Posteriormente, recibió un esquema individualizado de tratamiento para tuberculosis consistente en medicamentos mínimamente hemato-hepatotóxicos, similar al indicado en pacientes inmunosuprimidos. Desde entonces presenta baciloscopias negativas.

A case of a 48 year-old male with uncontrolled type 2 diabetes mellitus for the past ten years who presented pulmonary tuberculosis by clinical, radiographic signs and Mycobacterium tuberculosis sputum culture, sensitive to first line treatment drugs, is reported. He received standard treatment with isoniazid, rifampicin, ethambutol, pyrazinamide showing two months later drug hypersensitivity consisting in generalized skin rash, pruritus, positive Coombs anemia, eosinophilia and systemic symptoms compatible with DRESS syndrome (drug rash with eosinophilia and systemic symptoms). The antituberculous drugs were suspended and systemic antihistaminic drugs and corticoids were administered with remission and improvement of symptoms. Afterwards individualized treatment scheme for tuberculosis consisting in minimal hemato-hepatotoxic drugs similar to those indicated to immunosuppressed patients was indicated. Baciloscopies have been negative since.

Quilotórax bilateral asociado a linfoma no Hodgkin, folicular: génesis del quilotórax / Bilateral chylothorax associated to non-hodgkin's follicular lymphoma: the origin of chylothorax

Varón de 50 años, con 7 meses de enfermedad caracterizada por mialgias, astenia, y malestar general. cinco meses antes de ingresar al Hospital Dos de Mayo (HNDM), desarrolla derrame pleural derecho que requiere drenaje pleural (1500-2500 cc/día). Internado en el HNDM se descubre un derrame pleural bilateral con incremento de triglicéridos. Una tomografía espiral multicorte (TEM), de tórax con contraste demostró adenopatías mediastinales, derrame pleural bilateral, liquido al interior de la pleura mediastinal derecha posterior adyacente a D10-D11-D12, e imagen osteolítica en cuerpo vertebral de D11. Una biopsia de ganglio axilar izquierdo, reveló un Linfoma no Hodgkin (LNH), folicular de células grandes y pequeñas. Estando sometido a una dieta alta en triglicéridos de cadena media y aceite de oliva como suplemento el paciente recibió quimioterapia (Dexametasona, Ciclofosfamida, Doxorrubicina, Vincristina), siendo dado de alta después del primer ciclo, con programación de quimioterapias cada 3 semanas y toracocentesis evacuatorias periódicas condicionales. Después de 5 meses de tratamiento, el quilotórax bilateral desapareció.

This is the story of a 50 year-old male subject with a 7-month illness characterized by myalgia, fatigue, and malaise. 5 months before being admitted to Dos de Mayo National Hospital (HNDM), he developed right pleural effusion requiring pleural drainage (1500-2500 mL/day).While in HNDM, the patient developed bilateral pleural effusion with increased triglycerides. A multiple-slice contrast spiral CT (TEM) of the chest showed mediastinal lymph node enlargement, bilateral pleural effusion, and the presence of fluid within the right posterior mediastinal pleura adjacent to D10-D11-D12, and an osteolytic image in D11 vertebral body. A left axillary lymph node biopsy revealed non-Hodgkin lymphoma (NHL), follicular type with large and small cells. The patient received a diet rich in medium-chain triglycerides and olive oilas a supplement, and he also received chemotherapy (dexamethasone, cyclophosphamide, doxorubicin, vincristine), being discharged after the first cycle. Chemotherapy was scheduled to be administered every 3 weeks, and drainage thoracentesis were also scheduled to be performed during his probation period. After 5 months of treatment, bilateral chylothorax disappeared.

Paciente VIH positivo con tuberculosis sistémica y lesiones osteolíticas de la calvaria, semejando mieloma múltiple / Patient HIV positive with systemic tuberculosis and osteolytic calvarial lesions mimicking multiple myeloma

Varón de 33 años, soltero, sin ocupación fija, promiscuo, con historia de relaciones homosexuales, ingesta crónica de alcohol, consumo de tabaco, marihuana, pasta básica y clorhidrato de cocaína, desde los 18 años. Infectado por el virus de la inmunodeficiencia humana, recibía tratamiento irregular con terapia antirretroviral de gran actividad (Targa) entre 2006 y 2008, regularizada en los últimos 12 meses. Por presentar bacilo ácido alcohol resistente (BAAR) pansensible en esputo, inició en junio 2008 tratamiento antituberculoso [2RHZE/4(HR)2)], retirándosele la medicación 6 meses después por presentar BAAR pulmonar negativo. En marzo de 2009, percibió dolor lumbar intenso, dificultad para caminar, hipertrofia de ganglios cervicales, tos, fiebre. Un cultivo de secreción ganglionar cervical descubrió M. tuberculosis resistente a rifampicina. La imagenología mostró lesiones osteolíticas múltiples en cráneo y vértebras dorsolumbares y tumefacciones renitentes en cuero cabelludo, antebrazo derecho y parrilla costal izquierda. Tras descartarse mieloma múltiple y metástasis cancerosas, se añadió tratamiento antituberculosis multidrogo resistente al Targa, notándose dos meses después involución de las tumefacciones renitentes, de la fiebre y mejoría del estado general. Tras 16 meses de tratamiento supervisado, el paciente aumentó 7 kg de peso, habiendo desaparecido la sintomatología que presentaba. Se discute la fisiopatología de las lesiones osteolíticas cráneo-vertebrales en un paciente con coinfección por el virus de la inmunodeficiencia humana y tuberculosis.

This is the case of a 33 years old man with history of homosexual relations and heavy alcohol drinking. Tobacco, marijuana, cocaine, basic paste and cocaine hydrochloride consumption since age 18. Because of human immunodeficiency virus infection he received irregular treatment (2006-2008) with highly active antiretroviral therapy (HAAT), regulated in the past 12 months. As the patient showed positive resistant acid-fast bacilli he received since June 2008 standard antituberculous treatment [2RHZE/4(HR)2)] (R: rifampicin; H: isoniazid; Z: pirazinamide; E: ethambutol) that was withdrawn 6 months later when the patient showed pulmonary negative acid fast bacilli. In March 2009 he felt intense lumbar pain, difficulty in walking, hypertrophy of cervical lymph nodes, cough and fever. Cervical lymph node discharge culture disclosed M. tuberculosis resistant to rifampicin. Imagenology showed several lytic lesions in skull and thoraco-lumbar vertebrae; also renitent swellings in scalp, right forearm and left rib cage. After multiple myeloma and metastatic cancer were excluded, the patient received multidrug resistant tuberculosis treatment added to HAAT, showing two months later involution of renitent swellings, absence of fever and overall improvement. After 16 months of supervised treatment, the patient gained 7 kg and all symptomatology previously present dissappeared. We discuss the pathophysiology of craniovertebral osteolytic lesions in a patient with coinfection of human immunodeficiency virus and tuberculosis.