Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Análisis comparativo de la radiografía de tórax y la ecografía pulmonar para predecir el pronóstico intrahospitalario de pacientes ingresados por neumonía secundaria a SARS-CoV-2 (COVID-19) / Comparative analysis of chest radiography and lung ultrasound to predict intra-hospital prognosis of patients admitted for acute SARS-CoV-2 pneumonia (COVID-19)

Antecedentes: La ecografía torácica es una técnica novedosa para estratificar el riesgo de los pacientes COVID-19. Sin embargo, no existen datos que comparen dicha técnica con la radiografía de tórax, una técnica ampliamente utilizada en esta enfermedad.Pacientes y métodosAnálisis retrospectivo en pacientes estables COVID-19. Se compararon la escala de daño pulmonar radiológica de Schalekamp y ecográfica de LUZ-Score. El objetivo primario fue la muerte intrahospitalaria o la necesidad de ingreso en la UCI para tratamiento con ventilación mecánica.ResultadosSe reclutaron 138 pacientes. La mediana de la escala de Schalekamp fue de 2 (2) y la del LUZ-Score de 21 (10). No se objetivó una correlación significativa entre ambas escalas. Los pacientes con un LUZ-Score ≥21 puntos al ingreso presentaron peor función pulmonar y mayores concentraciones de LDH, PCR e interleucina-6. La escala radiológica de Schalekamp no logró identificar a una población de mayor riesgo. Únicamente la adición de la ecografía pulmonar a un modelo de valoración clínica mejoró de manera significativa el área bajo la curva para el objetivo primario (ABC 0,805 [IC95%: 0,662-0,948]; p≤0,001).ConclusionesNo se objetivó una correlación entre la afectación radiológica y la ecográfica. Únicamente la ecografía pulmonar identificó un subgrupo de pacientes con una mayor afectación clínico-analítica. La ecografía pulmonar mejoró el modelo de predicción clínico, mientras que la radiografía de tórax no añadió información relevante. (AU)

Background: Point of care lung ultrasound (POCUS) has been recently used to assess prognosis in COVID-19 patients. However, there are no data comparing POCUS and chest-X ray, a technique widely used.Patients and methodsRetrospective analysis in stable COVID-19 patients. Schalekamp radiological lung scale and LUZ-Score ultrasound scale were compared. Primary end-point was in-hospital death and/or need for Intensive Care Unit admission.ResultsA total of 138 patients were included. Median Schalekamp scale was 2 (2) and median LUZ-Score scale was 21 (10). No significant correlation was observed between both techniques. Patients with a LUZ-Score ≥21points at admission had worse lung function and higher concentrations of LDH, CRP and Interleuquine-6. Schalekamp scale failed to identify patients at a higher risk at admission for the primary end-point. Addition of POCUS to a previous clinical model, improved risk prediction (AUC 0.805 [95%CI: 0.662-0.948]; P=<.001).ConclusionsChest X-ray and POCUS showed no correlation at admission in this analysis. Only POCUS identified a group of patients with greater clinical and analytical involvement. POCUS improved, previous clinical model, while chest X-ray did not add relevant predictive information for the primary endpoint. (AU)

Comparative analysis of chest radiography and lung ultrasound to predict intra-hospital prognosis of patients admitted for acute SARS-CoV-2 pneumonia (COVID-19).

Background: Point of care lung ultrasound (POCUS) has been recently used to assess prognosis in COVID-19 patients. However, there are no data comparing POCUS and chest-X ray, a technique widely used. Patients and methods: Retrospective analysis in stable COVID-19 patients. Schalekamp radiological lung scale and LUZ-Score ultrasound scale were compared. Primary end-point was in-hospital death and/or need for Intensive Care Unit admission. Results: A total of 138 patients were included. Median Schalekamp scale was 2 (2) and median LUZ-Score scale was 21 (10). No significant correlation was observed between both techniques. Patients with a LUZ-Score ≥ 21 points at admission had worse lung function and higher concentrations of LDH, CRP and Interleuquine-6. Schalekamp scale failed to identify patients at a higher risk at admission for the primary end-point. Addition of POCUS to a previous clinical model, improved risk prediction (AUC 0.805 [95% CI: 0.662-0.948]; P = <0.001). Conclusions: Chest X-ray and POCUS showed no correlation at admission in this analysis. Only POCUS identified a group of patients with greater clinical and analytical involvement. POCUS improved, previous clinical model, while chest X-ray did not add relevant predictive information for the primary endpoint.

Antecedentes: La ecografía torácica es una técnica novedosa para estratificar el riesgo de los pacientes COVID-19. Sin embargo, no existen datos que comparen dicha técnica con la radiografía de tórax, una técnica ampliamente utilizada en esta enfermedad. Pacientes y métodos: Análisis retrospectivo en pacientes estables COVID-19. Se compararon la escala de daño pulmonar radiológica de Schalekamp y ecográfica de LUZ-Score. El objetivo primario fue la muerte intrahospitalaria o la necesidad de ingreso en la UCI para tratamiento con ventilación mecánica. Resultados: Se reclutaron 138 pacientes. La mediana de la escala de Schalekamp fue de 2 (2) y la del LUZ-Score de 21 (10). No se objetivó una correlación significativa entre ambas escalas. Los pacientes con un LUZ-Score ≥ 21 puntos al ingreso presentaron peor función pulmonar y mayores concentraciones de LDH, PCR e interleucina-6. La escala radiológica de Schalekamp no logró identificar a una población de mayor riesgo. Únicamente la adición de la ecografía pulmonar a un modelo de valoración clínica mejoró de manera significativa el área bajo la curva para el objetivo primario (ABC 0,805 [IC 95%: 0,662−0,948]; p ≤ 0,001). Conclusiones: No se objetivó una correlación entre la afectación radiológica y la ecográfica. Únicamente la ecografía pulmonar identificó un subgrupo de pacientes con una mayor afectación clínico-analítica. La ecografía pulmonar mejoró el modelo de predicción clínico, mientras que la radiografía de tórax no añadió información relevante.

Comparative analysis of chest radiography and lung ultrasound to predict intra-hospital prognosis of patients admitted for acute SARS-CoV-2 pneumonia (COVID-19). / Análisis comparativo de la radiografía de tórax y la ecografía pulmonar para predecir el pronóstico intrahospitalario de pacientes ingresados por neumonía secundaria a SARS-CoV-2 (COVID-19).

BACKGROUND: Point of care lung ultrasound (POCUS) has been recently used to assess prognosis in COVID-19 patients. However, there are no data comparing POCUS and chest-X ray, a technique widely used. PATIENTS AND METHODS: Retrospective analysis in stable COVID-19 patients. Schalekamp radiological lung scale and LUZ-Score ultrasound scale were compared. Primary end-point was in-hospital death and/or need for Intensive Care Unit admission. RESULTS: A total of 138 patients were included. Median Schalekamp scale was 2 (2) and median LUZ-Score scale was 21 (10). No significant correlation was observed between both techniques. Patients with a LUZ-Score ≥21points at admission had worse lung function and higher concentrations of LDH, CRP and Interleuquine-6. Schalekamp scale failed to identify patients at a higher risk at admission for the primary end-point. Addition of POCUS to a previous clinical model, improved risk prediction (AUC 0.805 [95%CI: 0.662-0.948]; P=<.001). CONCLUSIONS: Chest X-ray and POCUS showed no correlation at admission in this analysis. Only POCUS identified a group of patients with greater clinical and analytical involvement. POCUS improved, previous clinical model, while chest X-ray did not add relevant predictive information for the primary endpoint.

Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients: a prospective noninterventional study.

BACKGROUND: Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. METHODS: Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. RESULTS: 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4-9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16-26) points at admission versus 20 (16-27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98-0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42-20.90; p=0.013) were predictors for the primary end-point. CONCLUSIONS: LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification.

Performance Assessment of Software to Detect and Assist Prescribers with Antimicrobial Drug Interactions: Are all of them Created Equal?

BACKGROUND: Detecting and managing antimicrobial drug interactions (ADIs) is one of the facets of prudent antimicrobial prescribing. Our aim is to compare the capability of several electronic drug-drug interaction (DDI) checkers to detect and report ADIs. METHODS: Six electronic DDI checking platforms were evaluated: Drugs.com®, Medscape®, Epocrates®, Medimecum®, iDoctus®, and Guía IF®. Lexicomp® Drug Interactions was selected as the gold standard. Ten ADIs addressing different mechanisms were evaluated with every electronic DDI checker. For each ADI, we assessed five dimensions and calculated an overall performance score (maximum possible score: 10 points). The explored dimensions were sensitivity (capability to detect ADI), clinical effect (type and severity), mechanism of interaction, recommended action(s), and documentation (quality of evidence and availability of references). RESULTS: The electronic DDI checkers did not detect a significant proportion of the ADI assessed. The overall performance score ranged between 4.4 (Medimecum) and 8.8 (Drugs.com). Drugs.com was the highest ranked platform in four out of five dimensions (sensitivity, effect, mechanism, and recommended action). CONCLUSIONS: There is significant variability in the performance of the available platforms in detecting and assessing ADI. Although some ADI checkers have proven to be very accurate, others missed almost half of the explored interactions.

The Importance of a Multidisciplinary Approach in the Management of a Patient with Type I Gaucher Disease.

Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and for providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat, has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular and comprehensive follow up are necessary.