Tratamiento de la enfermedad tuberculosa pulmonar y extrapulmonar / Treatment of pulmonary and extrapulmonary tuberculosis

El tratamiento de la enfermedad tuberculosa busca un doble beneficio: un beneficio individual, centrado en la curación del paciente afecto de tuberculosis, y un beneficio colectivo, de la comunidad en la cual reside el paciente. Se exponen los diferentes regímenes de tratamiento tanto de la tuberculosis sensible a fármacos antituberculosos de primera línea como de la tuberculosis resistente. Se comentan las peculiaridades en cuanto al manejo de la tuberculosis pulmonar y extrapulmonar

The purpose of tuberculosis treatment is twofold: to provide an individual benefit centred on healing the patient with TB, and to provide a collective benefit to the community in which the patient resides. The different treatment regimens for tuberculosis sensitive to first-line antituberculosis drugs as well as resistant tuberculosis are examined and the peculiarities in the management of pulmonary and extrapulmonary tuberculosis are discussed

Treatment of pulmonary and extrapulmonary tuberculosis. / Tratamiento de la enfermedad tuberculosa pulmonar y extrapulmonar.

The purpose of tuberculosis treatment is twofold: to provide an individual benefit centred on healing the patient with TB, and to provide a collective benefit to the community in which the patient resides. The different treatment regimens for tuberculosis sensitive to first-line antituberculosis drugs as well as resistant tuberculosis are examined and the peculiarities in the management of pulmonary and extrapulmonary tuberculosis are discussed.

Retrospective study of tolerability and efficacy of linezolid in patients with multidrug-resistant tuberculosis (1998-2014) / Estudio retrospectivo sobre la tolerabilidad y eficacia de linezolid en pacientes con tuberculosis multirresistente (1998-2014)

INTRODUCTION: Although linezolid is known to be effective when used as an adjunct therapy in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), the clinical experience is limited. In this study the efficacy and adverse effects of linezolid treatment were evaluated. METHODS: A retrospective study of tolerability and efficacy of linezolid in MDR-TB patients was performed in Madrid, Spain. Demographic characteristics, microbiological and clinical features and data on treatment tolerability were collected. Regimens were constructed with a target of prescribing, at least, five anti-tuberculosis agents likely to be effective. Linezolid, at a dosage of 1200 or 600 mg daily, was included to complete the treatment if no other sensitive drugs were available. Vitamin B6 was used to reduce toxicity. Treatment outcome and clinical status at last contact were compared between patients with linezolid-containing regimens and with those without linezolid-containing regimens. RESULTS: During the period 1998-2014, 55 patients with MDR-TB received treatment. In 21 of these patients, linezolid was added. The median of linezolid administration was 23.9 months (IQT 13.1-24.7). Patients using linezolid showed a greater resistance to drugs, with a median of 6 (IQR 5-7) compared with those who did not use it, with a median of 4 drugs (IQR 3-5) (p < 0.001). The median time to sputum culture conversion of the patients in the linezolid group (73.5 days) did not differ significantly from those in the non-linezolid group (61 days) (p = 0.29). There were no significant differences in the outcomes of the two patient groups. There were no reported adverse events in 81% of patients assigned to linezolid therapy. Only four patients developed toxicity attributed to linezolid. The most serious adverse event in these patients was anemia observed in the two patients treated with 1200 mg per day. One of them also developed moderate paresthesia. In both cases the dosage was reduced to 600 mg per day, with improvement of the anemia and paresthesias. No patients stopped linezolid therapy. CONCLUSION: A daily dosage of 600 mg of linezolid was well tolerated without stopping treatment in any case. The efficacy of the treatment and the outcomes were similar in both the linezolid and non-linezolid group

INTRODUCCIÓN: Aunque es conocida la utilidad y la eficacia de linezolid cuando se administra para el tratamiento de pacientes con tuberculosis multirresistente (TB-MR), la experiencia clínica actual sigue siendo limitada. En este estudio se analiza la evolución, la eficacia y los efectos adversos del tratamiento con linezolid en pacientes con diagnostico de TB-MR. MÉTODO: Se realizó un estudio retrospectivo sobre la tolerabilidad y la eficacia de linezolid en pacientes diagnosticados de TB-MR en Madrid, España. Los regimenes de tratamiento se constituyeron con al menos 5 fármacos antituberculosos efectivos. Linezolid (a dosis de 1200 o 600 mg por día) se añadió para completar el tratamiento en los pacientes en los que no existían otros fármacos alternativos sensibles. Se utilizó vitamina B6 para reducir la toxicidad al tratamiento. Se comparó la evolución clínica de los pacientes y los resultados del tratamiento entre el grupo de pacientes tratados con linezolid y el grupo de pacientes que no fueron tratados con este fármaco. RESULTADOS: Entre 1998 y 2014, 55 pacientes fueron diagnosticados de TB-MR y recibieron tratamiento. En 21 pacientes fue necesaria la administración de linezolid. La media de tiempo de administración de linezolid fue de 23.9 meses (IQR 13.1-24.7). Los pacientes del grupo de linezolid presentaron mayor número de resistencias a fármacos con una mediana de 6 (IQR 5-7), respecto al grupo que no tomó Linezolid [4 fármacos (IQR 3-5)] (p < 0,001). No hubo diferencias significativas entre el tiempo de conversión del cultivo de esputo de los pacientes del grupo de linezolid (73,5 días) frente al del grupo sin linezolid (61 días) (p = 0,29). Tampoco hubo diferencias significativas en la evolución de los dos grupos de pacientes. El 81% de los pacientes que tomaron linezolid no experimentaron efectos adversos atribuidos a la administración de Linezolid. Sólo cuatro pacientes desarrollaron toxicidad secundaria al uso de linezolid. El efecto adverso más importante fue anemia que se presentó en los dos pacientes tratados con 1200 mg al día. Uno de ellos también desarrolló parestesias de grado moderado en miembros inferiores. En ambos casos, la dosis se redujo a 600 mg al día, con mejoría de la anemia y de las parestesias. CONCLUSIÓN: La dosis de 600 mg al día de linezolid fue bien tolerada sin necesidad de interrumpir el tratamiento en ningún caso. La eficacia del tratamiento y la evolución de los pacientes fueron similares en ambos grupos

Retrospective study of tolerability and efficacy of linezolid in patients with multidrug-resistant tuberculosis (1998-2014).

INTRODUCTION: Although linezolid is known to be effective when used as an adjunct therapy in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), the clinical experience is limited. In this study the efficacy and adverse effects of linezolid treatment were evaluated. METHODS: A retrospective study of tolerability and efficacy of linezolid in MDR-TB patients was performed in Madrid, Spain. Demographic characteristics, microbiological and clinical features and data on treatment tolerability were collected. Regimens were constructed with a target of prescribing, at least, five anti-tuberculosis agents likely to be effective. Linezolid, at a dosage of 1200 or 600 mg daily, was included to complete the treatment if no other sensitive drugs were available. Vitamin B6 was used to reduce toxicity. Treatment outcome and clinical status at last contact were compared between patients with linezolid-containing regimens and with those without linezolid-containing regimens. RESULTS: During the period 1998-2014, 55 patients with MDR-TB received treatment. In 21 of these patients, linezolid was added. The median of linezolid administration was 23.9 months (IQT 13.1-24.7). Patients using linezolid showed a greater resistance to drugs, with a median of 6 (IQR 5-7) compared with those who did not use it, with a median of 4 drugs (IQR 3-5) (p<0.001). The median time to sputum culture conversion of the patients in the linezolid group (73.5 days) did not differ significantly from those in the non-linezolid group (61 days) (p=0.29). There were no significant differences in the outcomes of the two patient groups. There were no reported adverse events in 81% of patients assigned to linezolid therapy. Only four patients developed toxicity attributed to linezolid. The most serious adverse event in these patients was anemia observed in the two patients treated with 1200 mg per day. One of them also developed moderate paresthesia. In both cases the dosage was reduced to 600 mg per day, with improvement of the anemia and paresthesias. No patients stopped linezolid therapy. CONCLUSION: A daily dosage of 600 mg of linezolid was well tolerated without stopping treatment in any case. The efficacy of the treatment and the outcomes were similar in both the linezolid and non-linezolid group.

Influence of concomitant antiretroviral therapy on the rate of sustained virological response to pegylated interferon plus ribavirin in hepatitis C virus/HIV-coinfected patients.

OBJECTIVES: To investigate whether concomitant antiretroviral therapy (ART) is a predictor of sustained virological response (SVR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with pegylated interferon plus ribavirin. METHODS: Three hundred and ten HIV/HCV-coinfected patients on pegylated interferon plus ribavirin treatment, 258 of them with concurrent ART, were included in this retrospective multicentre study. The predictors of SVR were evaluated. RESULTS: SVR was shown by 114 (37%) subjects. HCV genotype 2 or 3, plasma HCV-RNA load lower than 600 000 IU/mL, an exposure to the therapy against HCV infection > or =80% of the planned dose and baseline CD4 cell counts higher than or equal to 300/mm(3) were predictors of SVR. Likewise, patients without ART and those receiving a combination including tenofovir or stavudine plus lamivudine plus a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) showed a higher SVR rate than the subjects who were on other ART strategies at baseline [44%, 44% and 29%, respectively; adjusted odd ratio (95% CI) for no ART = 1.96 (1.07-4.76), P = 0.025, and for ART including tenofovir or stavudine plus lamivudine plus a PI or a NNRTI = 2.08 (1.16-3.70), P = 0.014]. CONCLUSIONS: The ART strategy on starting therapy with pegylated interferon plus ribavirin is a predictor of SVR in HIV/HCV-coinfected patients. Subjects without ART and those receiving combinations of a PI or a NNRTI with a nucleos(t)ide backbone of tenofovir or stavudine plus lamivudine respond better than those who receive other regimens.

Antiretroviral therapy based on protease inhibitors as a protective factor against liver fibrosis progression in patients with chronic hepatitis C.

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.