Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression. Objective: To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease. Design, Setting, and Participants: Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021. Interventions: Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529). Main Outcomes and Measures: The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation. Results: Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%). Conclusions and Relevance: Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown. Trial Registration: ClinicalTrials.gov Identifier: NCT04545060.

[Lung Ultrasound to Predict Unfavorable Progress in Patients Hospitalized for COVID-19]. / Predicción de evolución desfavorable en pacientes hospitalizados por COVID-19 mediante ecografía pulmonar.

OBJECTIVE: Thoracic ultrasound has been shown to be useful in the diagnosis of COVID-19 pulmonary involvement. Several scores for quantifying the degree of involvement have been described, although there is no evidence to show that they have any capacity for predicting unfavorable progress. METHODOLOGY: Prospective cohort study of patients hospitalized for COVID-19. The sample was stratified according to clinical course, and patients requiring invasive or non-invasive respiratory support were classified as having unfavorable progress. Biomarkers were analyzed at admission and on the same day that thoracic ultrasound was performed. Prognostic scales were also determined at admission. The ultrasound score was obtained in 8 or 14 areas, depending on the patient's ability to sit. RESULTS: We included 44 patients, 13 (29,5%) of whom subsequently needed ventilatory support. Eight areas were explored in all patients and 14 areas in 35 (79.5%). The most affected areas were the posterior lower lobes. Significant differences were found between the 2 groups on the SOFA and quick SOFA multidimensional scales, and PCR and LDH on the same day as thoracic ultrasound, and the ultrasound scores. The best area under the ROC curve (AUC) was obtained with the 14-area score, with a result of 0.88 (95% CI: 0.75-0.99). Its sensitivity and specificity for a cut-off score of 13.5 were 100% and 61.5%, respectively. CONCLUSIONS: The use of scores to quantify lung involvement measured by thoracic ultrasound provides useful information, facilitating risk stratification in patients hospitalized with COVID-19.

Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab.

BACKGROUND: Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease. METHODS: In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization. RESULTS: In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively). CONCLUSIONS: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.).

Predicción de evolución desfavorable en pacientes hospitalizados por COVID-19 mediante ecografía pulmonar / Lung Ultrasound to Predict Unfavorable Progress in Patients Hospitalized for COVID-19

OBJETIVO: La ecografía torácica ha mostrado ser útil para el diagnóstico de la afectación pulmonar por COVID-19. Para cuantificar el grado de afectación se han descrito varias escalas, aunque no existe evidencia de si su determinación podría tener alguna capacidad predictiva de evolución desfavorable. METODOLOGÍA: Estudio prospectivo de cohortes en el que se incluyó a pacientes ingresados por COVID-19. La muestra se estratificó en función de la evolución clínica, considerándose desfavorable en los pacientes que precisaron soporte respiratorio invasivo o no invasivo. Se analizaron biomarcadores al ingreso y el mismo día de la ecografía torácica, así como las escalas pronósticas al ingreso. Según la posibilidad de sedestación o no, se aplicó clasificación ecográfica en 8 o 14 áreas. RESULTADOS: Se incluyó a 44 pacientes, 13 (29,5%) con necesidad posterior de soporte ventilatorio. En todos se exploraron 8 áreas y en 35 (79,5%) las 14. Las zonas más afectadas fueron los lóbulos inferiores en la zona posterior. Se detectaron diferencias significativas entre los 2 grupos en las escalas multidimensionales SOFA y quick SOFA, la PCR y LDH del mismo día de la ecografía torácica y la puntuación de las escalas ecográficas. La mejor área bajo la curva ROC (AUC) se obtuvo con la escala de 14 áreas, que fue de 0,88 (IC 95%: 0,75-0,99). Su sensibilidad y especificidad para un punto de corte 13,5 fue del 100% y del 61,5%. CONCLUSIONES: El uso de escalas para cuantificar la afectación pulmonar mediante ecografía torácica proporciona información útil para facilitar la estratificación del riesgo en los pacientes hospitalizados con COVID-19

OBJECTIVE: Thoracic ultrasound has been shown to be useful in the diagnosis of COVID-19 pulmonary involvement. Several scores for quantifying the degree of involvement have been described, although there is no evidence to show that they have any capacity for predicting unfavorable progress. METHODOLOGY: Prospective cohort study of patients hospitalized for COVID-19. The sample was stratified according to clinical course, and patients requiring invasive or non-invasive respiratory support were classified as having unfavorable progress. Biomarkers were analyzed at admission and on the same day that thoracic ultrasound was performed. Prognostic scales were also determined at admission. The ultrasound score was obtained in 8 or 14 areas, depending on the patient's ability to sit. RESULTS: We included 44 patients, 13 (29,5%) of whom subsequently needed ventilatory support. Eight areas were explored in all patients and 14 areas in 35 (79.5%). The most affected areas were the posterior lower lobes. Significant differences were found between the 2 groups on the SOFA and quick SOFA multidimensional scales, and PCR and LDH on the same day as thoracic ultrasound, and the ultrasound scores. The best area under the ROC curve (AUC) was obtained with the 14-area score, with a result of 0.88 (95% CI: 0.75-0.99). Its sensitivity and specificity for a cut-off score of 13.5 were 100% and 61.5%, respectively. CONCLUSIONS: The use of scores to quantify lung involvement measured by thoracic ultrasound provides useful information, facilitating risk stratification in patients hospitalized with COVID-19

En respuesta a: «Resumen ejecutivo del Documento de consenso de GeSIDA sobre el control y la monitorización de la infección por el VIH» / In reply to: "Executive summary of the GeSIDA consensus document on control and monitoring of HIV-infected patients"

No disponible

Infección diseminada por Mycobacterium scrofulaceum en paciente en tratamiento con golimumab / Disseminated Mycobacterium scrofulaceum infection in a patient in treatment with golimumab

No disponible

In Vitro Activity of Tedizolid against Mycobacterium tuberculosis.

Tedizolid is a novel oxazolidinone with activities against Gram-positive microorganisms, including mycobacteria. We studied the in vitro activity of tedizolid against 120 Mycobacterium tuberculosis strains, including susceptible, first-line-resistant, and multidrug-resistant isolates. MIC was tested using the Bactec 960 MGIT system. MIC90 and MIC50 were 0.5 and 0.25 µg/ml, respectively, in susceptible and resistant strains. Tedizolid may be an alternative in the treatment of resistant M. tuberculosis.

Surveillance of Drug-Resistant Tuberculosis in Spain (2001-2015).

Multidrug-resistant tuberculosis (MDR-TB) is a cause of increasing concern. This study investigated first-line anti-TB drug resistance in Mycobacterium tuberculosis strains submitted to the Tuberculosis Reference Center in Córdoba (Spain) between 2001 and 2015. A total of 1,207 cultures were tested against first-line drugs using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 207 strains (17.2%), the greatest resistance being found in INH (5.3%) followed by streptomycin (3%), pyrazinamide (2.2%), rifampicin (1%), and ethambutol (0.2%). A total of 1.9% of strains were MDR-TB. Six strains displayed resistance to four drugs, and three strains to five drugs. In view of resistance observed, careful surveillance of drug resistance is recommended.

Evaluation of a new automated Abbott RealTime MTB RIF/INH assay for qualitative detection of rifampicin/isoniazid resistance in pulmonary and extra-pulmonary clinical samples of Mycobacterium tuberculosis.

A new automated real-time PCR assay for the detection of rifampicin (RIF) and isoniazid (INH) resistance in Mycobacterium tuberculosis (MTB) was evaluated. A total of 163 clinical samples (128 pulmonary and 35 extra-pulmonary) were processed using four PCR assay kits: Abbott RealTime MTB RIF/INH, Genotype MTBDRplus, Xpert/MTB RIF, and Anyplex MTB/MDR. The results of phenotypic drug-susceptibility testing using BACTECMGIT 960 were used as reference. The sensitivity and specificity of the new Abbott RealTime MTB RIF/INH assay in comparison with phenotypic testing was 96.3% (95%CI 87.32%-100%) for RIF and 100% (95%CI 99.3%-100%) for INH; the sensitivity was 78.8% (95%CI 66.8%-90.9%) and the specificity was 100% (95%CI 98.9%-100%). The Abbott RealTime MTB RIF/INH test could be a valid method for detecting the most common mutations in strains resistant to RIF and INH.

Executive summary: Pre-exposure prophylaxis for prevention of HIV infection in adults in Spain: July 2016 / Resumen ejecutivo: profilaxis pre-exposición en adultos para la prevención de la infección por VIH en España: Julio 2016

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out (AU)

Se ha demostrado que la administración de fármacos antirretrovirales a personas expuestas y no infectadas por el VIH puede reducir el riesgo de transmisión. La eficacia de la profilaxis pre-exposición obliga a considerar su inclusión en un programa integral de prevención de la transmisión del VIH, junto con otras medidas como el uso del preservativo, la formación y el consejo asistido y el tratamiento adecuado de las personas infectadas. En este documento, el Grupo de Estudio de SIDA (GeSIDA) de la SEIMC aporta su visión sobre este importante tema. Se presenta la evidencia disponible acerca de la utilidad de la PrEP en la prevención de la transmisión del VIH y se enumeran los elementos que deberían integrar un programa de PrEP, cuyo desarrollo y puesta en marcha sea factible y viable en nuestro medio (AU)

Executive summary: Pre-exposure prophylaxis for prevention of HIV infection in adults in Spain: July 2016.

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out.

Resistencias a fármacos en Mycobacterium tuberculosis / Antimicrobial resistance in tuberculosis

La resistencia a fármacos en tuberculosis no es un proble¬ma nuevo, pero la resistencia múltiple a los fármacos, despier¬ta cada día más interés. Nuestro estudio consistió en investi¬gar las resistencias a fármacos de las cepas de Mycobacterium tuberculosis aisladas en nuestro hospital Universitario que funciona como centro de referencia para el control de la tu¬berculosis en Andalucía, en el periodo 2001-2010. Hemos es¬tudiado las resistencias en 650 cultivos frente a los fármacos de primera y línea usando el sistema BACTEC MGIT 960. Detec¬tamos resistencias a 1ª línea en 142 cepas, (21,85%). De estas cepas la mayor resistencia se detectó isoniazida (7,38%) segui¬da de rifampicina y estreptomicina (3,85%), pirazinamida (2%), y etambutol (1,23%). En el caso de las cepas multirresistentes (MDR), estos valores son del 2%. Se encontró una cepa con resistencia a los cuatro fármacos. Las resistencias detectadas, aconsejan una vigilancia de las resistencias a los fármacos en tuberculosis (AU)

Although drug resistance in tuberculosis is by no means a new problem, multiple drug resistance is a cause of increasing concern. This study investigated first-line drug resistance in Mycobacterium tuberculosis strains isolated in a hospital en¬vironment and strains submitted as the Reference Center from 2000 to 2010. A total of 650 cultures were tested against first-line using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 142 strains, (21.85%). A total of 2% were multiresistant (MDR). Of the strains resistant to first-line drugs, the greatest resistance was found to isoniazid (7.38 %) followed by rifampin and streptomycin (3.85%), pyracinamide (2%), and ethambutol 1.23%. Only one strain was resistant to four drugs. Values. In view of the resistance observed, careful surveillance of drug resistance is recommended (AU)

[Antimicrobial resistance in tuberculosis]. / Resistencias a fármacos en Mycobacterium tuberculosis.

Although drug resistance in tuberculosis is by no means a new problem, multiple drug resistance is a cause of increasing concern. This study investigated first-line drug resistance in Mycobacterium tuberculosis strains isolated in a hospital environment and strains submitted as the Reference Center from 2000 to 2010. A total of 650 cultures were tested against first-line using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 142 strains, (21.85%). A total of 2% were multiresistant (MDR). Of the strains resistant to first-line drugs, the greatest resistance was found to isoniazid (7.38 %) followed by rifampin and streptomycin (3.85%), pyracinamide (2%), and ethambutol 1.23%. Only one strain was resistant to four drugs. Values. In view of the resistance observed, careful surveillance of drug resistance is recommended.

Factores clínicos asociados a aspergilosis pulmonar invasiva en pacientes con neumopatías crónicas y aislamiento respiratorio de Aspergillus spp / Clinical factors associated with invasive pulmonary aspergillosis in patients with chronic pneumopathies and respiratory isolation of Aspergillus spp

Fundamento y objetivo: Determinar variables clínicas para distinguir colonización de aspergilosis pulmonar invasiva (API) en pacientes con neumopatías crónicas y aislamiento respiratorio de Aspergillus spp. Pacientes y método: Estudio retrospectivo de cohortes donde se incluyeron pacientes con aislamiento respiratorio de Aspergillus spp. durante un período de 10 años. La API se definió mediante los criterios de Bulpa. Para determinar los factores de riesgo de API se recogieron variables clínicas y se realizó un análisis de regresión logística múltiple. Resultados: Se incluyeron 83 pacientes con aislamiento de Aspergillus spp. El 68,7% (n=57) de los pacientes presentaba enfermedad pulmonar respiratoria crónica, el 18% (n=15) fibrosis pulmonar y el 13,3% (n=11) asma bronquial. Veintidós pacientes (26,6%) reunieron criterios de API. El fluconazol (OR 4,49; IC 95% 1,5-13,4; p=0,007), la insuficiencia respiratoria grave (OR 4,64; IC 95% 1,46-14,72; p=0,009) y el tiempo de hospitalización (OR 1,05; IC 95% 1,01-1,1 p=0,006) se asociaron con mayor riesgo de API. Conclusiones: En los pacientes con neumopatías crónicas con aislamiento respiratorio de Aspergillus spp., el uso de fluconazol, la insuficiencia respiratoria grave y el tiempo de hospitalización se asocian con mayor riesgo de que el aislamiento se corresponda con API(AU)

Background and objective: To determine clinical variables to distinguish invasive pulmonary aspergillosis (IPA) from colonization in patients with chronic pneumopathies with positive culture of Aspergillus spp. in respiratory samples. Patients and methods: Retrospective cohort study including patients with respiratory isolations of Aspergillus spp. during a period of 10 years. IPA was evaluated according to the Bulpa criteria. Clinical variables were collected and a multiple logistic regression analysis was carried out. Results: Eighty-three patients with isolation of Aspergillus spp. from respiratory samples were included; 68.7% (n=57) of the patients had chronic obstructive pulmonary disease, 18% (n=15) pulmonary fibrosis and 13.3% (n=11) bronchial asthma. Twenty-two patients (26.6%) had IPA. The use of fluconazole (OR 4.49; CI 95% 1.5-13.4; P=0.007), severe respiratory failure (OR 4.64; CI 95% 1.46-14.72; P=0.009) and hospitalization time (OR 1.05; CI 95% 1.01-1.1; P=0.006) were associated with IPA. Conclusions: Prior use of fluconazole, severe respiratory failure and hospitalization time are associated with IPA in patients with chronic pneumopathies with respiratory isolation of Aspergillus spp(AU)

[Clinical factors associated with invasive pulmonary aspergillosis in patients with chronic pneumopathies and respiratory isolation of Aspergillus spp]. / Factores clínicos asociados a aspergilosis pulmonar invasiva en pacientes con neumopatías crónicas y aislamiento respiratorio de Aspergillus spp.

BACKGROUND AND OBJETIVE: To determine clinical variables to distinguish invasive pulmonary aspergillosis (IPA) from colonization in patients with chronic pneumopathies with positive culture of Aspergillus spp. in respiratory samples. PATIENTS AND METHODS: Retrospective cohort study including patients with respiratory isolations of Aspergillus spp. during a period of 10 years. IPA was evaluated according to the Bulpa criteria. Clinical variables were collected and a multiple logistic regression analysis was carried out. RESULTS: Eighty-three patients with isolation of Aspergillus spp. from respiratory samples were included; 68.7% (n=57) of the patients had chronic obstructive pulmonary disease, 18% (n=15) pulmonary fibrosis and 13.3% (n=11) bronchial asthma. Twenty-two patients (26.6%) had IPA. The use of fluconazole (OR 4.49; CI 95% 1.5-13.4; P=.007), severe respiratory failure (OR 4.64; CI 95% 1.46-14.72; P=.009) and hospitalization time (OR 1.05; CI 95% 1.01-1.1; P=.006) were associated with IPA. CONCLUSIONS: Prior use of fluconazole, severe respiratory failure and hospitalization time are associated with IPA in patients with chronic pneumopathies with respiratory isolation of Aspergillus spp.

Investigación de las resistencias a antimicrobianos en Enterococcus faecium / Investigation of antimicrobial resistance to Enterococcus faecium

Se llevo a cabo un estudio de resistencias a antimicrobianos de los aislamientos de Enterococcus faecium intrahospitalarios y extrahospitalarios del 2004 al 2010, procedentes de tres tipos de muestras: orinas, exudados y sangre, considerando una sola cepa por paciente. Se incluyeron en el estudio un total de 637 aislamientos de E. faecium. Para la identificación y el estudio de sensibilidades a antimicrobianos se utilizó el método semiautomatizado WIDER I. Se consideraron los criterios de sensibilidad y resistencia recomendados por el grupo MENSURA. La sensibilidad a betalactámicos fue del 48,05%, a linezolid del 100% y vancomicina del 99,46%. La resistencis a los aminoglucósidos osciló entre el 41,41 y 73,55%. Hemos encontrado 6 casos de resistencia a vancomicina, un caso extrahospitalario y cinco casos intrahospitalarios. Parece que la incidencia de E. faecium resistente a la vancomicina es un hecho hoy en día en aumento, que habría que vigilarlo(AU)

We performed a antibiotic resistance study on Enterococcus faecium isolated from intrahospitalary and extrahospitalary samples between 2004 and 2010. Three different samples were studied; urine, blood and wound swabs, considering a strain per patient. We included in the study a global amount of 637 E. faecium isolares. We employed semiautomatic system WIDER I for identification and sensitivity testing. We considered susceptibility and resistance criteria recommended by MENSURA group. We found a susceptibility rate of 48.05% to betalactams, 100% to linezolid, and 99.46% to vancomycin. The resistance to aminoglycosides ranged between 41.41 and 73.55%. We obtained 6 isolates resistant to vancomycin one of them from an extrahospitalary strain and five from intrahospitalary strains. It seems that vancomycin resistance should be controlled(AU)