Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation.

INTRODUCTION: In addition to respiratory support needs, patients' characteristics to guide indication or timing of corticosteroid treatment in COVID-19 patients are not completely established. This study aimed to evaluate the impact of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). METHODS: Between 9 March and 5 May 2020 (final follow-up on 2 July 2020), a retrospective cohort study was conducted in hospitalised patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers [IBs]: temperature ≥38℃, lymphocyte ≤800 cell/µL, C-reactive protein ≥100 mg/L, lactate dehydrogenase ≥300 units/L, ferritin ≥1000 mcg/L, D-dimer ≥500 ng/mL). Patients received 0.5-1.0 mg/kg of methylprednisolone for 5-10 days or standard of care. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ≥2 points improvement on a 7-item WHO-scale (Day 14), transfer to intensive care unit (ICU) (Day 28) and adverse effects. Kaplan-Meier method and Cox proportional hazard regression were implemented to analyse the time to event outcomes. RESULTS: A total of 142 patients (corticosteroid group n = 72, control group n = 70) were included. A significant reduction in 28-day all-cause mortality was shown with methylprednisolone in patients with respiratory support (HR: 0.15; 95% CI 0.03-0.71), with ≥3 (HR: 0.17; 95% CI 0.05-0.61) or ≥4 altered IB (HR: 0.15; 95% CI 0.04-0.54) and in patients with both respiratory support and ≥3 (HR: 0.11; 95% CI 0.02-0.53] or ≥4 altered IB (HR: 0.14; 95% CI 0.04-0.51). No significant differences were found in secondary outcomes. CONCLUSION: Intermediate to high doses of methylprednisolone, initiated between 5 and 12 days after symptom onset, was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ≥3 o ≥ 4 altered IB, independently of the need of respiratory support.

Las relaciones con la microbiología: la visión desde otras especialidades / Relationships with microbiology: the view from other specialties

Los grandes avances que se han producido en el conocimiento de la patología infecciosa, en parte favorecidos por el desarrollo tecnológico de las últimas décadas, junto con los cambios asistenciales actuales, han conducido a un nuevo escenario en el que, lejos del control de las enfermedades infecciosas, la microbiología clínica adquiere un protagonismo indiscutible. Más aún, este mismo panorama lleva implícita la colaboración de distintos profesionales que conviven en el mismo ámbito asistencial, siempre con comunidad de intereses y, en ocasiones, también con intereses contrapuestos. Superando los protagonismos individuales que puedan producirse en el día a día en nuestros hospitales, es obvio que todos ellos deben entenderse, no sólo porque la mejor atención a nuestros pacientes así lo requiere sino porque de la colaboración sinérgica se ha de derivar un mejor desarrollo profesional de todos. Desde este principio de enfoque multidisciplinario y de colaboración y respeto mutuo, parece oportuno que distintos profesionales relacionados con la patología infecciosa den su opinión acerca de cómo ven ellos la especialidad de la microbiología clínica: infectólogos, internistas, pediatras e intensivistas. A continuación se exponen las reflexiones, siempre hechas desde una perspectiva muy libre y personal, acerca de cómo enfocar las relaciones mutuas y seguir progresando en el desarrollo del conocimiento de la patología infecciosa en nuestro país. Preguntarse de dónde venimos para saber adónde vamos aparece de forma explícita o implícita en todas estas reflexiones

The major advances produced in infectious diseases, partly favored by technological development in the last few years, together with current changes in healthcare, have led to a new scenario in which, far from the control of infectious diseases, clinical microbiology has acquired an undoubted leading role. This new panorama implies collaboration among distinct health professionals within the same healthcare setting, with common and occasionally conflicting interests. Setting aside the individual differences that can be produced in the daily life of our hospitals, all health professionals should understand one another, not only because such cooperation is required for optimal patient care but also because synergistic collaboration among professions would improve professional development. Based on this principle of a multidisciplinary approach, collaboration and mutual respect, the moment seems opportune for the various professionals involved in infectious diseases (infectologists, internists, pediatricians and intensivists) to express their view of the specialty of clinical microbiology. The present article includes reflections, from a highly liberal and personal point of view, on how mutual relationships can be approached and on how greater knowledge of infectious diseases can continue to be gained in Spain. In all these reflections, the questions of where we come from and where we are going are explicit or implicit

[Future role of micafungin in the treatment of invasive mycoses caused by filamentous fungi]. / Papel futuro de la micafungina en el tratamiento de las micosis invasoras por hongos filamentosos.

BACKGROUND: Micafungin is a echinocandin. It inhibits beta-1,3-D-glucan synthesis, thus achieving fungicidal activity against virtually all Candida spp., including those resistant to fluconazole, and fungistatic activity against Aspergillus spp., as well as several but not all pathogenic molds. Results from in vitro studies, animal models, small clinical trials, hint at possible future indications such as invasive aspergillosis and empirical viantifungal therapy, although currently there is little information published. AIMS: To describe published data of micafungin as treatment against invasive mold infections, specially analysing its role in the inmunodepressed host and critical care setting. METHODS: A systematic review of literature using the principal medical search engines was performed. Terms such as micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy were crossed. Febrile neutropenia patients were excluded. RESULTS: Several studies in these setting were identified and were described in this review. Although there were no blinded randomized clinical trials published, treatment or prophylaxis of invasive aspergillosis and other invasive mould infections with micafungin described in open clinical studies were analyzed. CONCLUSIONS: Micafungin could play a future important role as a primary or rescue therapy, alone or in combination, in the treatment or prophylaxis of invasive fungal infections caused by moulds. New randomized clinical trials are needed to confirm their efficacy.

Papel futuro de la micafungina en el tratamiento de las micosis invasoras por hongos filamentosos / Future role of micafungin in the treatment of invasive mycoses caused by filamentous fungi

Antecedentes: La micafungina se ha estudiado de forma extensa en su actividad intrínseca frente a diferentes tipos de hongos, así como en su eficacia y seguridad en modelos experimentales y en ensayos clínicos en humanos frente a candidiasis invasora y candidemia. Menos conocida es su actuación frente a infecciones fúngicas invasoras (IFI) causadas por hongos filamentosos. Objetivos: Descripción y evaluación de los resultados obtenidos en los ensayos clínicos que han relacionado, de forma directa o indirecta, la micafungina con las micosis causadas por hongos filamentosos, especialmente con la aspergilosis invasora (AI), en pacientes con riesgo alto. Métodos: Búsqueda en la bibliografía médica de los artículos y las publicaciones relacionados, mediante los principales motores de rastreo y repertorios científico-médicos al uso (PubMed, EMBASE) utilizando diferentes cruzamientos y selecciones entre los términos clave de sondeo (micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy). Resultados: Se encuentran varios estudios que se clasifican para su valoración respecto al tratamiento de IFI por hongos filamentosos, especialmente los casos o las series que incluyen episodios de AI, y los concernientes a la profilaxis antifúngica de las IFI en pacientes de riesgo alto (inmunodeprimidos o críticos). Aunque también se registran los estudios basados en el tratamiento empírico con micafungina de la neutropenia febril, se evita comentarlos, debido al pequeño tamaño muestral, la heterogeneidad de los pacientes, la ausencia de descripción o confirmación de las IFI basales y el uso de marcadores subrogados, mezclando confusamente esta estrategia con la de anticipación. Conclusiones: Aun en ausencia de ensayos clínicos comparativos, aleatorizados y ciegos, se puede considerar que la micafungina es una alternativa eficaz y bien tolerada en el tratamiento de rescate de la AI, y probablemente también en el tratamiento primario, como alguna otra de las equinocandinas precedentes. Su actividad la ejerce tanto en monoterapia, como en tratamiento combinado, aunque con esta última es- trategia aún parecen mejorarse sus tasas de respuesta, tanto en las pruebas in vitro, como en los modelos in vivo y en algunos estudios en humanos. Ha demostrado tener una capacidad importante como agente profiláctico para prevenir las IFI “de brecha” en pacientes trasplantados de riesgo alto. Por último, aunque son necesarios ensayos clínicos aleatorizados en diferentes áreas, se le augura un interesante panorama en el futuro inmediato del tratamiento de las IFI por hongos filamentosos en población pediátrica y como tratamiento combinado con polienos, al menos en rescate, de determinadas zigomicosis, sin olvidar la trascendencia clínica del posible “efecto paradójico” y de las propiedades inmunofarmacológicas (AU)

Background: Micafungin is a echinocandin. It inhibits β-1,3-D-glucan synthesis, thus achieving fungicidal activity against virtually all Candida spp., including those resistant to fluconazole, and fungistatic activity against Aspergillus spp., as well as several but not all pathogenic molds. Results from in vitro studies, animal models, small clinical trials, hint at possible future indications such as invasive aspergillosis and empirical antifungal therapy, although currently there is little information published.
Aims: To describe published data of micafungin as treatment against invasive mold infections, specially analysing its role in the inmunodepressed host and critical care setting. Methods: A sistematic review of literature using the principal medical search engines was performed. Terms such as micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy were crossed. Febrile neutropenia`patients were excluded Results: Several studies in these setting were identified and were described in this review. Although there were no blinded randomized clinical trials published, treatment or prophylaxis of invasive aspergillosis and other invasive mould infections with micafungin described in open clinical studies were analyzed. Conclusions: Micafungin could play a future important role as a primary or rescue therapy, alone or in combination, in the treatment or prophylaxis of invasive fungal infections caused by moulds. New randomized clinical trials are needed to confirm their efficacy (AU)

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment.

BACKGROUND: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU). OBJECTIVE AND METHODS: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion. RESULTS AND CONCLUSIONS: Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole (<30 days). In contrast, pre-emptive therapy is based on the presence of surrogate markers.

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis.

BACKGROUND: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU). OBJECTIVES AND METHODS: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and a European expert panel discussion. RESULTS AND CONCLUSIONS: Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific. One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3 beta-D: glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult and is usually based on the evaluation of risk factors.

Infección y pie diabético. ¿Existen nuevas posibilidades terapéuticas? / Infection and diabetic foot. Are there any new therapeutic possibilities?

Introducción. Uno de los aspectos más graves de las úlceras del pie diabético es la infección, pues empeora su pronóstico y dificulta su tratamiento. El conocimiento de su gravedad, la detección precoz del microorganismo responsable y la determinación de su antibiograma son aspectos prioritarios en el tratamiento de estos pacientes. El uso frecuente de antibióticos en los pacientes con pie diabético hace que las resistencias antimicrobianas sean uno de los factores a tener en cuenta a la hora de elegir un antibiótico, especialmente para evitar un tratamiento empírico inadecuado con el aumento de morbilidad y mortalidad que conlleva. Esto ha hecho que se investiguen y desarrollen nuevo fármacos para el tratamiento de estas infecciones, como el linezolid o el ertapenem, ya en el mercado, o la tigeciclina, la daptomicina y la dalbavancina, en vías de comercialización. Desarrollo. Se analizan el papel y el impacto de estos nuevos antibióticos en las infecciones del pie diabético basándose en los recientes ensayos clínicos publicados. Conclusión. La utilización racional de los nuevos fármacos descritos puede mejorar los resultados de las infecciones del pie diabético

Introduction. One of the most serious aspects of diabetic foot ulcers is infection, since this leads to a poorer prognosis and makes treatment more complicated. Being aware of its severity, early detection of the microorganism causing the infection and determining its antibiogram are priority aspects in the treatment of these patients. The frequent use of antibiotics in patients with diabetic foot makes antimicrobial resistance a factor to be taken into account when it comes to choosing an antibiotic, especially to prevent administration of unsuitable empirical treatment with the increased morbidity and mortality this entails. This has led to research and development of new drugs for the treatment of these infections, as is the case for example of linezolid or ertapenem, which are already on the market, or tigecycline and dalbavancin, which are on their way to being commercialised in the future. Development. The role played by these new antibiotics and the impact they have on diabetic foot infections are analysed on the basis of recently reported clinical trials. Conclusions. The rational use of the new drugs described here can improve outcomes in cases of diabetic foot infection