Serological response to COVID-19 pneumonia and increasing severity over 18 months in a prospective cohort of hospitalized patients.

In this study, we present an 18-month serological follow-up of 294 patients with COVID-19 pneumonia. The aim was to assess the dynamics of serological response and its correlation with clinical worsening, as well as to describe clinical worsening determinants. Results of the study showed an early immunoglobulin M response, which clearly diminished starting at 4 months, but nonetheless, a small group of patients remained positive. As for immunoglobulin G, levels were higher up to 6 months in patients who presented clinical worsening during hospitalization. High titers of the immunoglobulin were maintained in all patients during follow-up, which would indicate that humoral immunity due to infection is long-lasting. Male sex, presence of myalgias and extensive radiological affectation were significantly correlated with clinical worsening.

Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.

BACKGROUND: Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. METHODS: Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36. FINDINGS: From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older, and results did not differ significantly between exposure groups. The safety profile of C-Tb was similar to that for the TST. INTERPRETATION: C-Tb delivered IGRA-like results in a field-friendly format. Being unaffected by BCG vaccination status, the C-Tb skin test might provide more accurate treatment guidance in settings where the TST is commonly used. FUNDING: Statens Serum Institut.

Sumario ejecutivo de la guía de práctica clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa / Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection

El uso de las pruebas de liberación de interferón-gamma para el diagnóstico de la infección tuberculosa está muy generalizado en España. Sin embargo, no se ha alcanzado un consenso respecto a su aplicación en situaciones clínicas específicas. Con el fin de redactar una guía de empleo en la práctica clínica, un grupo de expertos que incluyó a especialistas en enfermedades infecciosas, enfermedades respiratorias, microbiología, pediatría y medicina preventiva, junto con un experto en metodología, efectuaron una búsqueda sistemática en la literatura, sintetizaron los resultados, calificaron la calidad de las evidencias y formularon recomendaciones de acuerdo con la metodología Grading of Recommendations of Assessment Development and Evaluations. Este documento es una guía basada en la evidencia para el empleo de las pruebas de liberación de interferón-gamma en el diagnóstico de la infección tuberculosa en pacientes en riesgo de padecer tuberculosis o en los que se sospeche enfermedad activa. La guía será aplicable tanto en atención primaria y especializada como en salud pública

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health

Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection. / Sumario ejecutivo de la guía de práctica clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa.

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health.

Executive summary of the guidelines for the use of interferon-gamma release assays in the diagnosis of tuberculosis infection / Sumario Ejecutivo de la Guía de Práctica Clínica sobre el uso de las pruebas de liberación de interferón-gamma para el diagnóstico de infección tuberculosa

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guideline for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the GRADE (Grading of Recommendations of Assessment Development and Evaluations) methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at the risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health

Las técnicas de detección in vitro de interferón-gamma (IGRA, del inglés interferon-gamma release assays), están ampliamente implantadas para el diagnóstico de infección tuberculosa en España. Sin embargo, no hay consenso sobre su aplicación en diferentes escenarios clínicos. Para desarrollar una guía de práctica clínica sobre su uso, un grupo de trabajo compuesto por especialistas en enfermedades infecciosas, neumología, microbiología, pediatría y medicina preventiva, junto con un metodólogo, llevaron a cabo una búsqueda sistemática de la literatura, sintetizaron la evidencia y gradaron su calidad, y formularon las recomendaciones siguiendo el método GRADE (Grading of Recommendations of Assessment Development and Evaluations). Este documento proporciona una guía basada en la evidencia para el uso de los IGRA para el diagnóstico de infección tuberculosa en pacientes en riesgo de tuberculosis o con sospecha de enfermedad activa. Esta guía es aplicable en la atención especializada y primaria, y salud pública

Executive summary of the guidelines for the use of interferon-γ release assays in the diagnosis of tuberculosis infection.

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guideline for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the GRADE (Grading of Recommendations of Assessment Development and Evaluations) methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at the risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health.

Documento de consenso sobre la prevención y el tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico / Consensus Document on Prevention and Treatment of Tuberculosis in Patients for Biological Treatment

El riesgo de enfermar de tuberculosis ha aumentado en los pacientes con enfermedades inflamatorias crónicas que reciben tratamiento inmunosupresor, en particular en aquellos tratados con terapia anti-TNF (del inglés tumor necrosis factor). En estos pacientes es obligatoria la detección de la infección tuberculosa latente y el tratamiento de dicha infección, dirigido a reducir el riesgo de progresión a enfermedad tuberculosa. Este documento de consenso resume la opinión de expertos y los conocimientos actuales sobre tratamientos biológicos, incluidos los bloqueantes del TNF. Se establecen recomendaciones para la utilización de las técnicas de liberación de interferón-gamma (IGRA) y la prueba de la tuberculina (PT) para el diagnóstico y el tratamiento de la infección tuberculosa latent

Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to TB is mandatory in these patients. This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy

Consensus Document on Prevention and Treatment of Tuberculosis in Patients for Biological Treatment.

Tuberculosis risk is increased in patients with chronic inflammatory diseases receiving any immunosuppressive treatment, notably tumor necrosis factor (TNF) antagonists therapy. Screening for the presence of latent infection with Mycobacterium tuberculosis and targeted preventive treatment to reduce the risk of progression to TB is mandatory in these patients. This Consensus Document summarizes the current knowledge and expert opinion of biologic therapies including TNF-blocking treatments. It provides recommendations for the use of interferon-gamma release assays (IGRA) and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in these patients, and for the type and duration of preventive therapy.

Estudio comparativo de concordancia y costes entre la prueba de la tuberculina y QuantiFERON ®-TB Gold In-Tube en el diagnóstico de la infección latente tuberculosa en contactos de pacientes con tuberculosis pulmonar / Comparative study of concordance and costs between tuberculin skin test and QuantiFERON ®-TB Gold In-Tube in the diagnosis of latent tuberculosis infection among contacts of patients with pulmonary tuberculosis

Introducción: El diagnóstico de la infección latente tuberculosa (ILT) es posible realizarlo mediante la prueba de la tuberculina (PT) o bien a través de las denominadas técnicas de interferon-γ release assays (IGRAS, «análisis de liberación del interferón-γ»), siendo QuantiFERON®-TB Gold In-Tube (QF-G-IT) la más usada. Los IGRAS permiten evitar algunos inconvenientes de la PT, especialmente la reacción cruzada con la vacuna con bacilo de Calmette-Guérin (BCG). No obstante, también presentan algunos problemas, como son los derivados del coste de la técnica, así como el ser un método de laboratorio que precisa una infraestructura y experiencia adecuadas. No existe un claro consenso sobre cuál de las técnicas debería utilizarse de forma prioritaria para el diagnóstico de la ILT. Método: Se trata de un estudio comparativo entre la PT y la QF-G-IT en nuestra cohorte de contactos de pacientes con tuberculosis pulmonar durante el período de estudio (n = 101). Se realizó un análisis de la concordancia global y por grupos según los contactos estuvieran vacunados con BCG o no. Se realizó, además, un estudio de costes de ambas técnicas y de las estrategias diagnósticas basadas en ellas. Resultados: La concordancia entre la PT y la QF-G-IT fue aceptable en el global de la muestra, pero muy buena en el grupo de no vacunados. Se registraron muy pocos casos de valores indeterminados. El estudio de costes mostró que la PT era más económica que la QF-G-IT; sin embargo, al analizar el coste de las estrategias según cada técnica, la PT mostró un mayor coste-beneficio. Conclusión: Aconsejamos considerar QF-G-IT como la única y preferente técnica para el diagnóstico de la ILT en contactos convivientes, basados en una buena concordancia general entre ambas técnicas (más aún si eliminamos el efecto de la vacuna) y un estudio de costes favorable a QF-G-IT (AU)

Introduction: Recently diagnosis of latent tuberculosis infection (LTBI) can be made using the tuberculin skin test (TST) or by techniques known as interferon-γ release assays (IGRAS), being QuantiFERON®-TB Gold In-Tube (QF-G-IT) the most used. The IGRAS avoid some drawbacks of the TST, especially cross-reaction with bacillus Calmette-Guérin (BCG) vaccine, but also present some problems such as those arising from cost and the need of having an adequate infrastructure and experience. There is no clear consensus on which technique should be preferentially used for the diagnosis of LTBI. Methods: This is a comparative study between the TST and QT-G-IT in a cohort of contacts of patients with pulmonary tuberculosis during the study period. An analysis of global agreement and groups was performed according to whether the contacts were vaccinated with BCG or not. A study of costs of both techniques and diagnostic strategies based on these techniques was performed. Results: The agreement between TST and QF-G-IT was acceptable in the whole sample yet it was very good in the unvaccinated group. Few cases of indeterminate values were recorded. The cost study showed that TST was cheaper than QF-G-IT; however when we analyzed the cost of the strategies according to each technique, the QF-G-IT showed a better cost-benefit. Conclusion: We suggest considering QF-G-IT as the only preferred technique for the diagnosis of LTBI in household contacts, based on good overall agreement between the 2 techniques (even if we eliminate the effect of the vaccine) and a cost analysis favorable to QF-G-IT (AU)

Utilidad del Quantiferon-TB Gold in Tube en el cribado de la infección latente tuberculosa en personal sanitario / Usefulness of Quantiferon-TB Gold in Tube in screening for latent tuberculosis infection in health workers

INTRODUCCIÓN: El personal sanitario se considera un colectivo de riesgo por estar más expuesto a la enfermedad tuberculosa. La prueba de la tuberculina (PT) presenta el inconveniente del alto número de falsos positivos, sobre todo en pacientes vacunados con BCG. En los últimos años las técnicas denominadas IGRAS parecen mejorar estos inconvenientes, si bien plantean otros dilemas. Nuestro objetivo es analizar la concordancia de ambos test y realizar un estudio de coste-beneficio de las posibles estrategias diagnósticas. MATERIAL Y MÉTODOS: Entre enero de 2010 y octubre de 2011 se estudió todo el personal sanitario del Hospital Universitari Mútua Terrassa de nueva incorporación y aquellos que tenían su revisión laboral. También se estudiaron trabajadores que habían sido contactos de pacientes ingresados con tuberculosis, sin aislamiento inicial. En todos los casos se realizó la PT y paralelamente un Quantiferon-TB Gold in Tube® (QF-G-IT) en sangre. Se consideró positiva una PT ≥ 10 mm y un QF-G-IT > 0,35 IU/ml. Se descartó enfermedad tuberculosa en todos los profesionales mediante radiología de tórax. Se hizo un estudio de coste beneficio de 3 estrategias posibles de estudio de la infección latente tuberculosa (ILT). RESULTADOS: Se estudiaron 226 profesionales sanitarios, con una media de edad de 30,65 ± 16 años. Cuarenta y cuatro (19,4%) presentaban vacuna con BCG, y en 8 (3,5%) se desconocía. La PT fue positiva en 33 (14,6%) casos y el QF-G-IT en 17 (7,5%). En 15 casos ambos valores de la PT y del QF-G-IT fueron positivos y coincidentes. En 18 (8%) profesionales la PT fue positiva, con un valor de QF-G-IT negativo. La concordancia entre ambas pruebas fue del 91%, con un kappa de 0,55. En vacunados, la concordancia fue del 70,5%, con un kappa de 0,33, mientras que en no vacunados fue del 98,9%, con un kappa de 0,65. La estrategia de cribado de la ILT más económica fue la basada en la PT, pero seguida muy de cerca por la estrategia basada en la PT con reconfirmación de los positivos con QF-G-IT, que fue la que mostró un mejor coste-beneficio ya que reduce profilaxis innecesarias. CONCLUSIONES: El QF-G-IT parece ser una técnica adecuada en la detección de la ILT y permite detectar los falsos positivos de la PT debidos a la vacuna con BCG. En este colectivo el QF-G-IT podría ser la prueba idónea para detectar a los realmente infectados y evitar así quimioprofilaxis innecesarias. La estrategia que mostró ser más coste-beneficio fue la basada en la PT con reconfirmación de los casos positivos mediante QF-G-IT

INTRODUCTION: Healthcare workers (HW) are considered a risk group for exposure to tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in all HW. The Tuberculin test (TT) has been used up until now for LTBI screening, but gives a high number of false positives, especially in patients vaccinated with BCG. Diagnostic methods based on detection of specific gamma interferon (IGRA) have recently appeared on the market in order to improve these drawbacks, but pose other dilemmas. The aim of this study is to determine the agreement between the two types of test and to carry out a cost-benefit study of the possible diagnostic strategies. MATERIAL AND METHODS: All newly hired HW by the Hospital Universitari Mútua Terrassa between January 2010 and October 2011 we were included in the study, as well as those who had their occupational review. Workers who been in contact with patients admitted with tuberculosis before the initial isolation were also tested. In all cases a parallel TT and serum QuantiFeron-TB Gold-in-Tube® (QF-G-IT) assays were performed. TB disease was ruled out in all professional by chest X-ray. The TT was considered positive when it was equal to or more than 10 mm and if the QF-G-IT was 0.35 IU/mL. A cost-effectiveness analysis was designed with three possible strategies to detect LTBI in order to find the one with the best cost-benefit. RESULTS: A total of 226 HW were studied, with a mean age 30.65 ± 16, of whom 44 (19.4%) had previous BCG vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%) cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33, while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening strategies for LTBI diagnosis were hose based on TT, but followed closely by the strategy based on TT with reconfirmation of positives with QF-G-IT. CONCLUSIONS: QF-G-IT seems to be a very sensitive technique to detect LTBI and allows false positives due to TT to be detected, particularly in BCG vaccinated HW. In this group QF-G-IT could be the ideal test to detect truly infected staff, and avoid unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in TT with reconfirmation or rejection of positive cases by QF-G-IT

[Comparative study of concordance and costs between tuberculin skin test and QuantiFERON(®)-TB Gold In-Tube in the diagnosis of latent tuberculosis infection among contacts of patients with pulmonary tuberculosis]. / Estudio comparativo de concordancia y costes entre la prueba de la tuberculina y QuantiFERON(®)-TB Gold In-Tube en el diagnóstico de la infección latente tuberculosa en contactos de pacientes con tuberculosis pulmonar.

INTRODUCTION: Recently diagnosis of latent tuberculosis infection (LTBI) can be made using the tuberculin skin test (TST) or by techniques known as interferon-γ release assays (IGRAS), being QuantiFERON(®)-TB Gold In-Tube (QF-G-IT) the most used. The IGRAS avoid some drawbacks of the TST, especially cross-reaction with bacillus Calmette-Guérin (BCG) vaccine, but also present some problems such as those arising from cost and the need of having an adequate infrastructure and experience. There is no clear consensus on which technique should be preferentially used for the diagnosis of LTBI. METHODS: This is a comparative study between the TST and QT-G-IT in a cohort of contacts of patients with pulmonary tuberculosis during the study period. An analysis of global agreement and groups was performed according to whether the contacts were vaccinated with BCG or not. A study of costs of both techniques and diagnostic strategies based on these techniques was performed. RESULTS: The agreement between TST and QF-G-IT was acceptable in the whole sample yet it was very good in the unvaccinated group. Few cases of indeterminate values were recorded. The cost study showed that TST was cheaper than QF-G-IT; however when we analyzed the cost of the strategies according to each technique, the QF-G-IT showed a better cost-benefit. CONCLUSION: We suggest considering QF-G-IT as the only preferred technique for the diagnosis of LTBI in household contacts, based on good overall agreement between the 2 techniques (even if we eliminate the effect of the vaccine) and a cost analysis favorable to QF-G-IT.

[Usefulness of Quantiferon-TB Gold in Tube® in screening for latent tuberculosis infection in health workers]. / Utilidad del Quantiferon-TB Gold in Tube(®) en el cribado de la infección latente tuberculosa en personal sanitario.

INTRODUCTION: Healthcare workers (HW) are considered a risk group for exposure to tuberculosis. Screening for latent tuberculosis infection (LTBI) is mandatory in all HW. The Tuberculin test (TT) has been used up until now for LTBI screening, but gives a high number of false positives, especially in patients vaccinated with BCG. Diagnostic methods based on detection of specific gamma interferon (IGRA) have recently appeared on the market in order to improve these drawbacks, but pose other dilemmas. The aim of this study is to determine the agreement between the two types of test and to carry out a cost-benefit study of the possible diagnostic strategies. MATERIAL AND METHODS: All newly hired HW by the Hospital Universitari Mútua Terrassa between January 2010 and October 2011 we were included in the study, as well as those who had their occupational review. Workers who been in contact with patients admitted with tuberculosis before the initial isolation were also tested. In all cases a parallel TT and serum QuantiFeron-TB Gold-in-Tube(®) (QF-G-IT) assays were performed. TB disease was ruled out in all professional by chest X-ray. The TT was considered positive when it was equal to or more than 10mm and if the QF-G-IT was 0.35 IU/mL. A cost-effectiveness analysis was designed with three possible strategies to detect LTBI in order to find the one with the best cost-benefit. RESULTS: A total of 226 HW were studied, with a mean age 30.65 ± 16, of whom 44 (19.4%) had previous BCG vaccination history, and 8 (3.5%) unknown. The TT was positive in 33 (14.6%) cases and the QF-G-IT in 17 (7.5%). The values of the TT and QF-G-IT were both positive in 15 cases. In 18 (8%) The TT was positive in 18 (8%) of cases with a negative QF-G-IT value. The agreement between the two tests was 91%, with a Kappa of 0.55. In vaccinated cases, the correlation was 70.5%, with a Kappa of 0.33, while in unvaccinated it was 98.9% with a Kappa of 0.65. The cheapest screening strategies for LTBI diagnosis were those based on TT, but followed closely by the strategy based on TT with reconfirmation of positives with QF-G-IT. CONCLUSIONS: QF-G-IT seems to be a very sensitive technique to detect LTBI and allows false positives due to TT to be detected, particularly in BCG vaccinated HW. In this group QF-G-IT could be the ideal test to detect truly infected staff, and avoid unnecessary chemoprophylaxis. The most cost-benefit strategy was those based in TT with reconfirmation or rejection of positive cases by QF-G-IT.

Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating enterococcus faecalis infective endocarditis.

BACKGROUND: The aim of this study was to compare the effectiveness of the ampicillin plus ceftriaxone (AC) and ampicillin plus gentamicin (AG) combinations for treating Enterococcus faecalis infective endocarditis (EFIE). METHODS: An observational, nonrandomized, comparative multicenter cohort study was conducted at 17 Spanish and 1 Italian hospitals. Consecutive adult patients diagnosed of EFIE were included. Outcome measurements were death during treatment and at 3 months of follow-up, adverse events requiring treatment withdrawal, treatment failure requiring a change of antimicrobials, and relapse. RESULTS: A larger percentage of AC-treated patients (n = 159) had previous chronic renal failure than AG-treated patients (n = 87) (33% vs 16%, P = .004), and AC patients had a higher incidence of cancer (18% vs 7%, P = .015), transplantation (6% vs 0%, P = .040), and healthcare-acquired infection (59% vs 40%, P = .006). Between AC and AG-treated EFIE patients, there were no differences in mortality while on antimicrobial treatment (22% vs 21%, P = .81) or at 3-month follow-up (8% vs 7%, P = .72), in treatment failure requiring a change in antimicrobials (1% vs 2%, P = .54), or in relapses (3% vs 4%, P = .67). However, interruption of antibiotic treatment due to adverse events was much more frequent in AG-treated patients than in those receiving AC (25% vs 1%, P < .001), mainly due to new renal failure (≥25% increase in baseline creatinine concentration; 23% vs 0%, P < .001). CONCLUSIONS: AC appears as effective as AG for treating EFIE patients and can be used with virtually no risk of renal failure and regardless of the high-level aminoglycoside resistance status of E. faecalis.

Diagnosis of tuberculosis infection by tuberculin skin test and a whole-blood interferon-γ release assay in patients considered for anti-tumor necrosis factor-α therapy.

To assess the performance of QuantiFERON®-TB Gold in-Tube (QFT-GIT; Cellestis, Carnegie, Australia) and tuberculin skin test (TST) in patients with immune-mediated inflammatory diseases (IMID), before anti-tumor necrosis factor-α (TNF-α) therapy, and to compare the results with those from the healthy population. Three hundred fourteen subjects (214 with IMID and 100 controls) underwent simultaneous QFT-GIT and TST. QFT-GIT was positive in 21% of IMID patients and in 16% of controls (P = 0.29). Among IMID patients, 21% tested positive by QFT-GIT and 24%, by TST (P = 0.30). Positive QFT-GIT results were not affected by immunosuppressive therapy (odds ratio, 0.78; 95% confidence interval [CI], 0.36-1.68; P = 0.52). Agreement between both tests in those patients who tested positive by one of the tests was 50% (95% CI, 37.2-62.8). QFT-GIT is useful for identifying IMID patients requiring treatment of latent tuberculosis before anti-TNF therapy. However, given the poor agreement between TST and QFT-GIT, we advocate a strategy of simultaneous testing to optimize diagnostic sensitivity.

IFN-γ response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection.

BACKGROUND: Individuals infected with human immunodeficiency virus (HIV) have an increased risk of progression to active tuberculosis following Mycobacterium tuberculosis infection. The objective of the study was to determine IFN-γ responses for the detection of latent tuberculosis infection (LTBI) with QuantiFERON-TB GOLD In Tube (QFT-G-IT) and T-SPOT.TB in HIV patients, and evaluate the influence of CD4 cell count on tests performance. METHODS: We studied 75 HIV patients enrolled for ongoing studies of LTBI with T-SPOT.TB, QFN-G-IT and TST. Mean CD4 cell counts ± standard deviation was 461.29 ± 307.49 cells/µl. Eight patients had a BCG scar. RESULTS: T-SPOT.TB, QFN-G-IT and TST were positive in 7 (9.3%), 5 (6.7%) and 9 (12%) cases, respectively. Global agreement between QFN-G-IT and T-SPOT.TB was 89% (κ = 0.275). The overall agreement of T-SPOT.TB and QFN-G-IT with TST was 80.8% (κ = 0.019) and 89% (κ = 0.373), respectively. We have found negative IFN-γ assays results among 2 BCG-vaccinated HIV-infected individuals with a positive TST. In non BCG-vaccinated patients, QFN-G-IT and TST were positive in 5 cases (7.5%) and T-SPOT.TB in 7 (10.4%). In contrast, in BCG-vaccinated patients, only TST was positive in 4/8 (50%) of the cases. The differences obtained in the number of positive results between TST and both IFN-γ assays in BCG vaccinated patients were significant (95% CI 3-97%, p = 0.046), however, the confidence interval is very wide given the small number of patients. In patients with CD4< 200, we obtained only one (5%) positive result with T-SPOT.TB; however, QFN-G-IT and TST were negative in all cases. On the contrary, percentages of positive results in patients with CD4> 200 were 10.9% (6/55), 9.1% (5/55) and 16.4% (9/55) with T-SPOT.TB, QFN-G-IT and TST, respectively. CONCLUSIONS: IFN-γ tests have the benefit over TST that are less influenced by BCG vaccination, consequently they are more specific than TST. Although our number of patients with advance immunosuppression is limited, our study suggests that IFN-γ assays are influenced with level of immunosuppression. The use of IFN-γ assays could be a helpful method for diagnosing LTBI in HIV population.

Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone.

BACKGROUND: High-level aminoglycoside resistance (HLAR) that precludes bactericidal synergism with penicillins or glycopeptides and nephrotoxicity related to aminoglycoside treatment are major problems in treating Enterococcus faecalis endocarditis. OBJECTIVE: To evaluate the efficacy and safety of ampicillin plus ceftriaxone for treating endocarditis due to E. faecalis with and without HLAR. DESIGN: Observational, open-label, nonrandomized, multicenter clinical trial. SETTING: 13 centers in Spain. PATIENTS: 21 patients with HLAR E. faecalis endocarditis and 22 patients with non-HLAR E. faecalis endocarditis. All were at risk for nephrotoxicity related to aminoglycoside use. INTERVENTION: 6-week course of intravenous ampicillin, 2 g every 4 hours, plus intravenous ceftriaxone, 2 g every 12 hours. MEASUREMENTS: Clinical and microbiological outcomes. RESULTS: The clinical cure rate at 3 months was 67.4% (29 of 43 patients) among all episodes. During treatment, 28.6% of patients with HLAR E. faecalis endocarditis and 18.2% of patients with non-HLAR E. faecalis endocarditis died of infection-related causes. The rate of clinical and microbiological cure in patients who completed the protocol was 100% in the HLAR E. faecalis endocarditis group. No episodes of breakthrough bacteremia occurred, although there were 2 relapses in the non-HLAR E. faecalis endocarditis group. Treatment was withdrawn in 1 case because of fever and skin rash. LIMITATIONS: The study had a small sample and was observational. CONCLUSION: The combination of ampicillin and ceftriaxone is effective and safe for treating HLAR E. faecalis endocarditis and could be a reasonable alternative for patients with non-HLAR E. faecalis endocarditis who are at increased risk for nephrotoxicity.