Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Positive Culture and Prognosis in Patients With Sepsis: A Prospective Cohort Study.

PURPOSE: To analyze the prognostic role of positive cultures in patients with sepsis. METHODS: A prospective cohort study in a tertiary referral hospital in Medellín, Colombia. Adults older than 18 years of age with a bacterial infection diagnosis according to Centers for Disease Control criteria and sepsis (evidence of organ dysfunction) were included. A logistic regression model was used to determine the association between positive cultures and hospital mortality, and a Cox regression with a competing risk modeling approach was used to determine the association between positive cultures and hospital stay as well as secondary infections. RESULTS: Overall, 408 patients had positive cultures, of which 257 were blood culture, and 153 had negative cultures. Patients with positive cultures had a lower risk of mortality (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.27-0.68), but this association was not maintained after adjusting for confounding factors (OR, 0.56; 95% CI, 0.31-1.01). No association was found with the hospital stay (adjusted subhazard ratio [SHR], 1.06; 95% CI, 0.83-1.35). There was no association between positive cultures and the presence of secondary infections (adjusted SHR, 0.99; 95% CI, 0.58-1.71). CONCLUSION: Positive cultures are not associated with prognosis in patients with sepsis.

Evaluación y manejo del riesgo cardiovascular en infección por VIH. Consenso de expertos ACIN / Evaluation and management of cardiovascualr risk in VIH infection: Expert consensus of ACIN (Colombian Association of Infectious Diseases)

Los pacientes con infección por VIH tienen una mayor incidencia de eventos cardiovasculares en comparación con la población general; los factores que contribuyen al incremento del riesgo de eventos cardiovasculares son la prevalencia de factores de riesgo cardiovascular tradicionales (FRCV), la infección por VIH que condiciona tanto un proceso de inflamación crónica como alteración de la función endotelial y la exposición a los antirretrovirales. Los factores que deben ser objeto de intervención son los FRCV tradicionales, en especial la alta tasa de fumadores entre este grupo de pacientes, la tamización y tratamiento de HTA, el síndrome metabólico y el acceso temprano a la terapia antirretroviral con medicamentos con mayor perfil de seguridad . Esta guía pretende proveer información y recomendaciones en el ámbito nacional acerca de la relación entre la infección por VIH/SIDA (Síndrome de Inmunodeficiencia Adquirida), uso de antirretrovirales y riesgo cardiovascular.

Patients with VIH infection have greater risk for cardiovascular diseases compared to general population. Risk factors that increase the frequency of cardiovascular events are: presence of cardiovascular traditional risk factors, chronic inflammation by HIV that impairs endothelial function and the exposure to antiretrovirals. The factors that should be the target for intervention are the traditional know cardiovascular factors such, especially high rate of smokers, screening and treatment for hypertension, metabolic syndrome and early access to HAART. The present guidelines provides information about the use of antiretrovirals in patients with HIV and its relation with cardiovascular risk.

Tigeciclina en infecciones de piel y tejidos blandos complicadas / Tigecycline in complicated skin and soft-tissue infection

Objetivo: evaluar la mejor evidencia actual disponible para generar recomendaciones con respecto a la efectividad y seguridad del uso de tigeciclina en adultos con infección de piel y tejidos blandos (IPTB). Materiales y métodos: se realizó una revisión sistemática de la literatura, seleccionando los metaanálisis y experimentos clínicos controlados (ECCs), los cuales se valoraron utilizando la herramienta SIGN (Scottish Intercollegiate Guidelines Network.), con el fin de generar tablas de evidencia según GRADE de los estudios de tigeciclina en la indicación de IPTB, para posteriormente utilizar un proceso Delphi modificado para calificar las diferentes recomendaciones. Resultados: la revisión sistemática se incluyeron 9 metaanálisis que incluyeron 5 estudios clínicos aleatorizados con 1873 pacientes, y de ellos 952 asignados al brazo de tigeciclina, no mostró inferioridad frente a los comparadores en curación clínica (RR= 0.76 IC95% 0,57 - 1.03), curación microbiológica (RR= 0.92 IC95% 0,61 - 1.38), eventos adversos serios RR 1,41 (IC95%0,97 a 2,35), ni mortalidad RR 1,9 (IC95%0,84 a 4,3). La tigeciclina puede relacionarse con mayor frecuencia de eventos adversos leves de origen gastrointestinal. Conclusión: en pacientes adultos con IPTB, se considera que el uso de tigeciclina en monoterapia en pacientes no críticamente enfermos es equivalente en eficacia a otras opciones terapéuticas antimicrobianas. Se debe considerar especialmente como terapia de ajuste en pacientes con infecciones polimicrobianas.

Objective: To assess current best evidence available to generate recommendations regarding the effectiveness and safety of tigecycline use in adults with skin and soft-tissue infections (SSTIs). Materials and methods: A systematic review of the literature was conducted by selecting meta-analyzes and controlled clinical trials (CCTs), which were assessed using the SIGN tool (Scottish Intercollegiate Guidelines Network) in order to generate evidence tables according to GRADE of studies of tigecycline in the SSTIs indication, and then using a modified Delphi Method to score the different recommendations. Results: Nine meta-analyzes were included compounded by five randomized clinical trials with a sample size of 1873 patients, where 952 patients were assigned to tigecycline. The group of patients with tigecycline showed no inferiority to the comparator in clinical cure (RR = 0.76 95% CI 0.57 - 1.03), microbiologic cure (RR = 0.92 95% CI 0.61 - 1.38), serious adverse events RR 1, 41 (95% CI 0.97 to 2.35) or mortality RR 1.9 (95% CI 0.84 to 4.3). Tigecycline may be related to increased frequency of minor adverse events of gastrointestinal origin. Conclusion: In adult patients with SSTIs, it is considered that the use of tigecycline in monotherapy in non-critically ill patients is equivalent in effectiveness to other antimicrobial treatment options. It should be especially considered as an adjustment therapy in patients with polymicrobial infections.

Tigeciclina en infecciones intraabdominales complicadas / Tigecycline in complicated intra-abdominal infections

Objetivo: evaluar la mejor evidencia actual disponible para generar recomendaciones, con respecto a la efectividad y seguridad del uso de tigeciclina en adultos con infección intraabdominal complicada. Materiales y métodos: se realizó una revisión sistemática de la literatura, seleccionando los metaanálisis y experimentos clínicos controlados, los cuales se valora- ron utilizando la herramienta SIGN, con el fin de generar tablas de evidencia según GRADE de los estudios de tigeciclina en la indicación infección intraabdominal complicada, para posteriormente utilizar un proceso Delphi modificado para calificar las diferentes recomendaciones con el fin de generar un consenso. Resultados: se analizaron los resultados basados en la revisión sistemática de la literatura en la que se incluyeron 5 metaanálisis que cumplieron los criterios de selección comparando tigeciclina con otros tratamientos antibióticos en infección intraabdominal complicada; de los cuales, 2711 pacientes recibieron al menos una dosis del antibiótico (1382 tigeciclina y 1389 el comparador) y en los que no se observaron diferencias estadísticamente significativas en los desenlaces evaluados al comparar tigeciclina con otros antibióticos. Conclusión: en pacientes adultos con infección intraabdominal complicada, se considera que el uso de tigeciclina en monoterapia es equivalente en eficacia y seguridad a otras opciones terapéuticas antimicrobianas y no representa un exceso de mortalidad en comparación a otros antibióticos

Objective: To assess current best evidence available to generate recommendations regarding the effectiveness and safety of tigecycline use in adults with complicated intra-abdominal infection (cIAIs). Materials and methods: We conducted a systematic review of published meta-analysis that evaluated tigecycline compared to other antimicrobials and included the indication of cIAI. Quality of the evidence was evaluated by using the SIGN tool (Scottish Intercollegiate Guidelines Network) according to GRADE, and final recommendations were assessed by a modified Delphi Method in order to develop a consensus. Results: Five meta-analyzes met the selection criteria comparing tigecycline with other antibiotic treatments in complicated intra-abdominal infection. Five randomized clinical trials comprised in these meta-analysis included 2711 patients that received at least one dose of antibiotic (1382 tigecycline and 1389 the comparator regimen), We found no statistically significant differences in the evaluated outcomes by comparing tigecycline with other antibiotics, including clinical and microbiologic efficacy, safety and drug related mortality Conclusion: In adult patients with cIAIs, the use of tigecycline as monotherapy is equivalent in effectiveness to other antimicrobial therapeutic options and does not represent an increase in mortality compared to other antibiotics.

Consenso Colombiano para la estratificación, diagnostico, Tratamiento y Prevención de la Infección por citomegalovirus en Pacientes Adultos con trasplante renal / Colombian consensus for stratification, diagnosis, treatment and prevention of cytomegalovirus infection in adults patients with renal transplant

El citomegalovirus es una de las principales causas de infección y enfermedad en receptores de trasplante renal, con un notorio impacto en términos de morbilidad, mortalidad y costos. Sin embargo, no existe en Colombia una práctica clínica estandarizada entre los centros de trasplante, por lo cual, es de suma importancia disponer de guías con el fin de orientar la estratificación, el diagnóstico de laboratorio, el tratamiento y la prevención de la infección y enfermedad por citomegalovirus en pacientes adultos con trasplante renal. A través de la metodología ADAPTE para la evaluación de calidad y transculturización de guías de práctica clínica a nuestro medio, un grupo multidisciplinario realizó una revisión sistemática de la literatura: se seleccionaron las guías internacionales, las cuales fueron evaluadas con el instrumento AGREE II en términos de calidad. Con la guía base seleccionada se buscó la evidencia existente para contestar a las preguntas, de acuerdo con el método de desarrollo de recomendaciones GRADE. Se realizaron recomendaciones para la estratificación, el diagnóstico, el tratamiento y la prevención de la infección y enfermedad por citomegalovirus en pacientes adultos con trasplante renal en Colombia.

Cytomegalovirus is a primary cause of infection and illness in patients who have had renal transplantation, with a significant impact on morbidity, mortality and economic costs. However, there is no standardized clinical practice in transplant centers in Colombia, and it is important to have guidelines to stratify, diagnose, treat and prevent cytomegalovirus infection and disease. Through ADAPTE's methodology for the quality evaluation and adaptation of clinical practice guidelines in our setting, a multidisciplinary group carried out a systematic review of the medical literature, selecting international guidelines that were evaluated with the AGREE-II instrument in terms of quality. With each selected guideline, an evidence table was constructed and the GRADE strategy was performed to develop recommendations. Recommendations related to stratification, laboratory diagnosis, treatment and prevention of infections and disease caused by cytomegalovirus in adult transplant patients were developed.

Tuberculous Lymphadenitis and Parotitis.

Tuberculous lymphadenitis is the most common extrapulmonary manifestation of disseminated tuberculosis (TB). It is considered to be the local manifestation of the systemic disease that has disseminated to local lymph nodes, but a high index of suspicion is needed for the diagnosis, because there are several infectious and noninfectious diseases that can mimic the same clinical picture. In recent years, different diagnostic methods have been introduced, including fine-needle aspiration cytology, which has emerged as a simple outpatient diagnostic procedure that replaced the complete excisional node biopsy, and a number of molecular methods which have greatly improved diagnostic accuracy. This chapter covers the most actual knowledge in terms of epidemiology, clinical manifestations, pathogenesis, and treatment and emphasizes current trends in diagnosis of tuberculous lymphadenitis. TB parotid gland involvement is extremely rare, even in countries in which TB is endemic. Because of the clinical similarity, parotid malignancy and other forms of parotid inflammatory disease always take priority over the rarely encountered TB parotitis when it comes to differential diagnosis. As a result, clinicians often fail to make a timely diagnosis of TB parotitis when facing a patient with a slowly growing parotid lump. This chapter highlights the most important features of this uncommon disease.

Follow-up results of isoniazid chemoprophylaxis during biological therapy in Colombia.

The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. The aim of this study was to present the follow-up results for isoniazid (INH) chemoprophylaxis in patients receiving different biological therapies. In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between 2 and 9 months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. A total of 221 patients, 122 females (55.2 %), with a mean age of 46.8 ± 11.3 years (16-74) were enrolled. LTBI was identified in 218 patients (98.7 %), all of whom received INH chemoprophylaxis. Seven patients (3.2 %) developed active tuberculosis, and 32 (17.2 %) patients developed intolerance or toxicity related to INH. Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivation in individuals with LTBI, but toxicity must be monitored during follow-up.

Conferencia clínico-patológica (CPC): paciente con malformación cardíaca congénita y endocarditis infecciosa / Clinico-pathological conference (CPC): patient with congenital heart malformation and infective endocarditis / Conferência clínico patológica (CPC): paciente com malformação cardíaca congênita e endocardites infecciosa

Se presenta el caso de un hombre de 17 años, sin antecedentes de importancia, quien consultó por deterioro de su clase funcional, fatigabilidad y disnea, de un mes de evolución, además de fiebre y síndrome de respuesta inflamatoria sistémica (SIRS), en quien se documentaron una malformación congénita de novo tipo situs inversus con levocardia y una comunicación interventricular (CIV), asociadas a transposición de grandes vasos; durante la hospitalización recibió varios tratamientos con antibióticos sin aislamiento microbiológico ni identificación de la causa de su descompensación hemodinámica. En el examen posmortem se identificó endocarditis por Aspergillus spp., con embolia a diferentes órganos.

We present the case of a 17 year-old-man, with no remarkable past medical history, who had a one month history of worsening functional class, fatigability and dyspnea, in addition to fever and systemic inflammatory response syndrome (SIRS); a de-novo congenital heart malformation, situs inversus type, with levocardia and a ventricular septal defect (VSD) associated with transposition of great vessels were documented. During hospitalization he received several antibiotic treatments without microbiological isolation or identification of the cause of hemodynamic decompensation. An Aspergillus endocarditis with emboli to different organs was identified in the post-mortem examination.

Se apresenta o caso de um homem de 17 anos, sem antecedentes de importância, quem consultou por um mês de evolução de deterioração de sua classe funcional, fatigabilidade e dispneia, além de febre e síndrome de resposta inflamatória sistémica (SIRS) em quem se documentaram uma malformação congênita de novo tipo situs inversus com levocardia e uma comunicação interventricular (CIV), associada a transposição de grandes copos; durante a hospitalização recebeu vários tratamentos com antibióticos sem isolamento microbiológico nem identificação da causa de sua descompensação hemodinâmica. No exame post-mortem se identificou endocardites por Aspergillus spp., com embolia a diferentes órgãos.

Conferencia clínico-patológica (CPC): trasplantado renal con nódulos pulmonares / Clinicopathological conference (CPC): renal transplant recipient with pulmonary nodules

Se presenta el caso de un hombre de 41 años de edad, trasplantado renal en 2005, quien ingresó al hospital por 10 días de evolución de fiebre, diarrea y síntomas respiratorios. Durante su evolución se documentó la presencia de un nódulo violáceo en la piel, varios nódulos pulmonares y úlceras en el colon; con una fuerte sospecha de infección micótica debido a sus antecedentes, se inició terapia antifúngica, pero finalmente falleció por insuficiencia respiratoria.

We report the case of a 41 year-old man, who had a renal transplantation in 2005. He was admitted to the hospital because of 10 days of fever, diarrhea and respiratory symptoms. During his stay, a nodular lesion in the skin, several pulmonary nodules and colon ulcers were documented; due to his past medical history he was highly suspicious of having a fungal infection; antifungal therapy was started, but he died due to respiratory insufficiency.