The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19.

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥4 was found to be the best cutoff point for predicting respiratory failure.

Utilidad de las escalas de sepsis para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 fuera de las Unidades de Cuidados Intensivos / The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19

El presente estudio retrospectivo observacional tiene como objetivo analizar la utilidad de las escalas SOFA (Sequential Organ Failure Assessment), qSOFA (Quick SOFA), NEWS (National Early Warning Score ) y Quick NEWS para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 atendidos fuera de la Unidad de Cuidados Intensivos (UCI). Se incluyeron 237 adultos con COVID-19 hospitalizados seguidos durante un mes o hasta su fallecimiento. El fallo respiratorio se definió como un cociente PaO2/FiO2 ≤ 200 mmHg o la necesidad de ventilación mecánica. Setenta y siete pacientes (32,5%) desarrollaron fallo ventilatorio; 29 (12%) precisaron ingreso en UCI, y 49 fallecieron (20,7%). La discriminación del fallo ventilatorio fue algo mayor con la puntuación NEWS, seguida de la SOFA. En cuanto a la mortalidad, la puntuación SOFA fue más exacta que las otras escalas. En conclusión, las escalas de sepsis son útiles para predecir el fallo respiratorio y la muerte en COVID-19. Una puntuación ≥ 4 en la escala NEWS sería el mejor punto de corte para predecir fallo respiratorio (AU)

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure (AU)

[The early use of sepsis scores to predict respiratory failure and mortality in non-ICU patients with COVID-19]. / Utilidad de las escalas de sepsis para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 fuera de las Unidades de Cuidados Intensivos.

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure.

Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

PURPOSE: There are few data in the literature regarding sepsis or septic shock due to extended-spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. METHODS: Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. Three cohorts were created for analysis: global, empirical-therapy and targeted-therapy cohorts. RESULTS: 367 septic patients were analysed. Overall mortality was 43.9% at 30 days. Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. ß-lactam/ß-lactamase inhibitor (BLBLI) combinations were the most empirically used drug (43.6%), followed by carbapenems (29.4%). Empirical therapy was active in vitro in 249 (67.8%) patients, and escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences in survival were reported in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. CONCLUSIONS: BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality. Comorbidities, severity scores, source of infection and antibiotic therapy escalation were important determinants of unfavorable outcome.

Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis.

OBJECTIVE: Combining a macrolide or a fluoroquinolone to beta-lactam regimens in the treatment of patients with moderate to severe community-acquired pneumonia is recommended by the international guidelines. However, the information in patients with bacteraemic pneumococcal pneumonia is limited. METHODS: A propensity score technique was used to analyze prospectively collected data from all patients with bacteraemic pneumococcal pneumonia admitted from 2000 to 2015 in our institution, who had received empirical treatment with third-generation cephalosporin in monotherapy or plus macrolide or fluoroquinolone. RESULTS: We included 69 patients in the monotherapy group and 314 in the combination group. After adjustment by PS for receiving monotherapy, 30-day mortality (OR 2.89; 95% CI 1.07-7.84) was significantly higher in monotherapy group. A higher 30-day mortality was observed in monotherapy group in both 1:1 and 1:2 matched samples although it was statistically significant only in 1:2 sample (OR: 3.50 (95% CI 1.03-11.96), P = 0.046). CONCLUSIONS: Our study suggests that in bacteraemic pneumococcal pneumonia, empirical therapy with a third-generation cephalosporin plus a macrolide or a fluoroquinolone is associated with a lower mortality rate than beta-lactams in monotherapy. These results support the recommendation of combination therapy in patients requiring admission with moderate to severe disease.

Time-to-positivity, type of culture media and oxidase test performed on positive blood culture vials to predict Pseudomonas aeruginosa in patients with Gram-negative bacilli bacteraemia.

OBJECTIVE: The aim of this study was to determine the usefulness of oxidase test and time-to-positivity (TTP) in aerobic and anaerobic blood culture vials to detect the presence of Pseudomonas aeruginosa in patients with Gram-negative bacilli (GNB) bacteraemia. METHODS: TTP was recorded for each aerobic and anaerobic blood culture vial of monomicrobial bacteraemia due to GNB. Oxidase test was performed in a pellet of the centrifuged content of the positive blood culture. An algorithm was developed in order to perform the oxidase test efficiently taking into account TTP and type of vial. RESULTS: A total of 341 episodes of GNB bacteraemia were analysed. Sensitivity, specificity, positive predictive value and negative predictive value of the oxidase test performed on positive vials with GNB to predict P. aeruginosa were 95%, 99%, 91%, and 99%, respectively. When growth was first or exclusively detected in anaerobic vials, P. aeruginosa was never identified hence the performance of the oxidase test could be avoided. When growth was only or first detected in aerobic vials, a TTP≥8h predicted P. aeruginosa in 37% or cases (63 of 169), therefore oxidase test is highly recommended. CONCLUSIONS: Oxidase test performed onto positive blood culture vials previously selected by TTP and type of vials is an easy and inexpensive way to predict P. aeruginosa. In most cases, this can lead to optimization of treatment in less than 24 hours.

Risk factors associated with high linezolid trough plasma concentrations.

AIM: The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin. METHODS: Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed. RESULTS: 34.6% patients had a Cmin >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD <40 mL/min. There were more patients co-treated with rifampin in the group with low Cmin. The only factor independently associated with Cmin >8 was the renal function. Patients with an eGF < 40 mL/min had significantly higher Cmin than those with eGF > 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109). CONCLUSIONS: High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

Staphylococcus aureus bacteremic pneumonia.

Staphylococcus aureus bacteremic pneumonia is an uncommon cause of hospitalization, with a high mortality rate. However, published reports are scarce and have included a small number of cases. All patients with S. aureus bacteremic pneumonia were prospectively collected in our institution from 2000 to 2014, and a retrospective revision was performed to identify risk factors associated with methicillin resistance and to update the mortality of this entity. A total of 98 patients were admitted: 57.1 % were due to methicillin-susceptible S. aureus (MSSA) and 42.8 % due to methicillin-resistant S. aureus (MRSA). In 40 patients (40.8 %), the infection was community acquired. Thirteen were ventilator-associated pneumonia episodes. The most frequent comorbidities were chronic lung disease (34.7 %), chronic renal failure (31.6 %), diabetes mellitus (29.6 %), and cardiovascular disease (31.6 %). Septic shock was present in 46 patients (46.9 %). The 30-day mortality was 46.9 %. MRSA infections occurred in older patients, more frequently with cardiovascular diseases, and they had received antibiotic treatment in the previous month more often than MSSA-infected patients. Patients with infection due to MSSA presented more frequently with septic shock, but they received more frequently appropriate empirical antibiotic therapy than patients with MRSA pneumonia (96 % vs. 38.1 %), and no differences in mortality were observed between both groups. In conclusion, S. aureus bacteremic pneumonia is a severe infection that, nowadays, affects people with comorbidities and the mortality is still high.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

INTRODUCTION: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. METHODS AND ANALYSIS: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. ETHICS AND DISSEMINATION: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. TRIAL REGISTRATION NUMBER: NCT01898338.

Community-onset bacteraemia of unknown origin: clinical characteristics, epidemiology and outcome.

Bacteraemia of unknown origin is prevalent and has a high mortality rate. However, there are no recent reports focusing on this issue. From 2005 to 2011, all episodes of community onset bacteraemia of unknown origin (CO-BSI), diagnosed at a 700-bed university hospital were prospectively included. Risk factors for Enterobactericeae resistant to third-generation cephalosporins (3GCR-E), Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus spp, and predictors of mortality were assessed by logistic regression. Out of 4,598 consecutive episodes of CO-BSI, 745 (16.2 %) were of unknown origin. Risk factors for S. aureus were male gender (OR 2.26; 1.33-3.83), diabetes mellitus (OR 1.71; 1.01-2.91) and intravenous drug addiction (OR 17.24; 1.47-202); for P. aeruginosa were male gender (OR 2.19; 1.10-4.37) and health-care associated origin (OR 9.13; 3.23-25.83); for 3GCR-E was recent antibiotic exposure (OR 2.53; 1.47-4.35), while for enterococci, it was recent hospital admission (OR 3.02; 1.64-5.55). Seven and 30-day mortality were 8.1 % and 13.4 %, respectively. Age over 65 years (OR 2.13; 1.28-3.55), an ultimately or rapidly fatal underlying disease (OR 4.15; 2.23-7.60), bone marrow transplantation (OR 4.07; 1.24-13.31), absence of fever (OR 4.45; 2.25-8.81), shock on presentation (OR 10.48; 6.05-18.15) and isolation of S. aureus (OR 2.01; 1.00-4.04) were independently associated with mortality. In patients with bacteraemia of unknown origin, a limited number of clinical characteristics may be useful to predict its aetiology and to choose the appropriate empirical treatment. Although no modifiable prognostic factors have been found, management optimization of S. aureus should be considered a priority in this setting.

Phase transformations in Sr0.8Ba0.2CoO2.5 brownmillerite: correlation between structure and transport properties.

An oxygen-defective perovskite oxide with the title composition has been prepared by soft-chemistry procedures followed by quenching in liquid N(2) from 900 degrees C. This polycrystalline sample has been characterized by temperature-dependent X-ray (XRPD) and neutron powder diffraction (NPD), thermal analysis, electrical conductivity and thermal expansion measurements, in order to correlate the physico-chemical properties and the structural features. At room temperature (RT), the sample adopts an orthorhombic brownmillerite-like structure defined in the Ibm2 space group, containing layers of CoO(6) octahedra alternating with layers of CoO(4) tetrahedra along the b axis. This phase is stable between room temperature and 350 degrees C, where a topotactic intake of oxygen increases the coordination of the tetrahedra to octahedral, with change of the space group to Pnma, as unveiled by the in-situ NPD study. This intermediate phase has been identified for the first time. At 653 degrees C, this phase irreversibly transforms to a hexagonal "H" phase. At 920 degrees C, a cubic perovskite phase "C" is identified, which is transformed again, upon cooling, into the "H" phase at 774 degrees C. The features of the very distinct coordination polyhedra present in the different polymorphs have been correlated with the transport properties. There is a substantial increment of the conductivity at 350 degrees C, upon the oxygen insertion process, concomitant with a contraction of the axial Co-O bonds of the octahedral CoO(6) units and the transformation of the tetrahedra into octahedra, also characterized by dilatometry measurements. The dramatic reduction of the conductivity above 700 degrees C is connected with the transformation to the "H" polymorph, with a complete oxygen sublattice and a face-sharing octahedral framework with a poor 1D electronic conduction. In Sr(0.8)Ba(0.2)CoO(2.5), the plateau of stability of the 3C-like structure, with useful transport properties in the range of sigma = 50-60 S cm(-1), is extended up to 650 degrees C with respect to the pristine SrCoO(2.5). By heating above 900 degrees C, the conductivity abruptly rises when the sample is entering the cubic perovskite region, characterized by a three-dimensional vertex-sharing network of CoO(6) octahedra. The total conductivity displays a maximum value of 75 S cm(-1) at 900 degrees C, which increases during the cooling run, exhibiting a typical metallic behaviour. Moreover, in this cubic phase, the oxygen atoms show large thermal factors of 5.5 A(2), suggesting a considerable mobility and a mixed conductor behaviour.

[Blood fractionation based on the extraction of the buffy-coat layer. Analysis of our results]. / Fraccionamiento sanguíneo basado en la extracción de la capa leucoplaquetaria. Análisis de nuestros resultados.

PURPOSE: To compare a procedure of blood processing via a quadruple bag for the preparation of white-cell-poor blood components with the results obtained with triple-bag-system, in order to adopt it as routine in our blood centre. MATERIAL AND METHODS: Blood was collected in 289 quadruple-bag-system containing 63 mL of CPD as anticoagulant and 100 mL of SAG M solution as additive for the red cells. We used 237 standard quadruple-bags supplied by Fenwal (195) and NPBI (42), and 52 of the top-and-bottom system supplied by Fenwal. Blood separation was made automatically by CompomatR (NPBI) and platelet concentrates were prepared from the buffy-coat fraction. Standard bags were processing as follows: After the first centrifugation of the whole blood (28,800 g), the plasma was transferred into the 300-mL bag until the interface of red cells and plasma was detected; then approximately 80 mL of plasma and buffy-coat (BC) were collected into the 100-mL satellite bag. Top-and-bottom bags were centrifuged at 43,500 g., the red-cells were transferred into the bottom-bag containing SAGM, and plasma was transferred into the top-bag. The buffy-coat fraction remains in the original bag. In both procedures, platelet concentrates were prepared from buffy-coat fraction. After the centrifugation of this fraction (1,400 g and 1,600 g), the supernatant (concentrated platelets in plasma) was transferred into a 300-mL bag and the bag with the residual buffy-coat was then discarded. 287 triple-bags were separated in the traditional way, using platelet-rich plasma (PRP) as a source for the preparation of platelet concentrate (PC). Volumes were measured by weigh and specificity gravity. Platelet, leukocytes and red-cells were counted in the Coulter-Counter (STKR.Izasa). T-Student test and Chi2 test were used for statistical analysis and p < 0.05 was taken as a significant difference between samples. RESULTS: The three kinds of quadruple-bags showed results very homogeneous with little differences. For all brand of bags packed-red-cells showed a volume of 300 +/- 2.9 mL, EVF of 51.9 +/- 0.7%. The recovery of red cells into the packed red cells and of platelets into the platelet concentrate was 90 +/- 0.4 percent and 69 +/- 2 percent respectively, of the original value. White cells in the packed red cells were 9.7 +/- 03 x 10(9) with recovery of 30.1 +/- 1.4 percent of the original value; statistical difference was found in comparison with triple bags PRC (p < 0.001). The PC volumes averaged 71 +/- 1 mL and the overall mean platelet concentration was 77 +/- 2 x 10(9). Eighty three percent of PC contained more than 55 x 10(9). White cells contamination of platelet concentrates was 0.283 +/- 0.039 x 10(9), with a recovery of 9.5 +/- 1.5 percent of the leukocytes present in the whole blood. This value is below the threshold that prevents febrile reactions and microaggregate formation. The plasma yield in the quadruple-bag system was much greater than that in the triple-bag system (p < 0.001). With this process we removed about 77 +/- 0.5 percent of the plasma present in the original unit in comparison with 56 +/- 1 percent removed in that of the triple-bag system. CONCLUSION: With this procedure leukocyte-poor blood components are obtained in which more of 90 percent original white cells have been removed, with a red-cell recovery of 90 percent. Moreover, the plasma yield is also excellent.

[Critical analysis of the routine use of the direct antiglobulin test in 22,517 cross-matching tests]. / Análisis crítico del empleo rutinario de la prueba de la antiglobulina directa (DAT) en 22,517 pruebas cruzadas.

Routine performance of the direct antiglobulin test (DAT) in pretransfusion testing (PT) is controversial. To evaluate its usefulness, we review the positive DATs found in 22,517 PT performed in our center in the last five years. DAT was positive in 330 PT (1.4%). Eluate studies gave information, not obtained from the rest of PT, in 6 cases. DAT predictive value is low (1.8% of the positive DATs, 0.02% of all PT). Although this predictive value is low, we keep on follow including DAT in PT but we have reduced eluate studies to 1) positive DAT of untransfused patients (to get information of the DAT prior to transfusion and to detected autoimmune haemolytic anaemias) and 2) positive DAT of previously transfused patients with previous negative DAT or changes in its reactivity (for the prompt detection of clinically significant antibodies).

Hepatic and intestinal formation of polar sterols in vivo in animals fed on a cholesterol-supplemented diet.

In rats fed on a diet containing 1% cholesterol for 24 h, the decrease in hepatic non-saponifiable lipid synthesis, cholesterogenesis and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was accompanied by an increase in the proportion of newly synthesized polar sterols in vivo. In these animals there was also a strong inverse correlation between the proportion of polar sterols in the non-saponifiable lipid and hepatic HMG-CoA reductase activity. A similar correlation was not observed in animals fed on a normal diet. Cholesterogenesis in the intestine was not as sensitive to inhibition by dietary cholesterol as was that in the liver, and there was no increase in the polar-sterol content of the newly synthesized non-saponifiable-lipid fraction.

A relationship between the activities of hepatic lanosterol 14 alpha-demethylase and 3-hydroxy-3-methylglutaryl-CoA reductase.

At 1-2 h after intragastric administration of ketoconazole, a cytochrome P-450 inhibitor, to rats, there was a 50-60% decrease in the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Inhibition reached a maximum at 6-12 h after the drug was given, but after 24 h enzyme activity was stimulated by 60%. The rates of synthesis of hepatic non-saponifiable lipids in vivo showed a similar time-dependent pattern of change. During the first few hours after drug administration, the hepatic cytochrome P-450-dependent metabolism of lanosterol was suppressed in vivo. However, 24 h after treatment, this activity was stimulated, an effect which was also observed by pre-treatment of the rats with the drug for several days. Suppression of hepatic HMG-CoA reductase and lanosterol 14 alpha-demethylase activities was accompanied by a relative increase in the accumulation of labelled polar sterols in the liver in vivo. In the intestine, ketoconazole also resulted in a rapid decline in the rate of synthesis of non-saponifiable lipids and an inhibition of lanosterol 14 alpha-demethylation in vivo. However, in contrast with the liver, there was no stimulation of non-saponifiable lipid synthesis after 24 h.