Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. Methods This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Results Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. Conclusions MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. Methods This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Results Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. Conclusions MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission

Risk Factors and Outcomes of Acute Graft Pyelonephritis with Bacteremia Due to Multidrug-Resistant Gram-Negative Bacilli among Kidney Transplant Recipients

Acute graft pyelonephritis (AGP) is the leading cause of bloodstream infection in kidney transplant (KT) recipients. The prevalence of urinary tract infections caused by multidrug-resistant (MDR) Gram-negative bacilli is increasing. This 14-year prospective observational study sought to determine the clinical characteristics, risk factors, and outcomes of AGP with bacteremia due to MDR Gram-negative bacilli. Overall, 278 episodes of AGP with bacteremia due to MDR Gram-negative and non-MDR Gram-negative bacilli were identified and compared in 214 KT recipients; MDR Gram-negative bacilli were the cause in 28.4%. Overall 30-day mortality was low (1.1%). Risk factors independently associated with AGP due to MDR Gram-negative bacilli were male sex (OR 3.08; 95%CI 1.60-5.93), previous episode of bacteremic AGP (OR 2.11, 95%CI 1.09-4.09), prior antibiotic therapy in the preceding month (OR 2.47, 95%CI 1.33-4.57), and nosocomial acquisition (OR 2.03, 95%CI 1.14-3.62). Forty-three percent of MDR Gram-negative episodes received inappropriate empirical antibiotic therapy. The risk factors identified in this study may help physicians when selecting empirical antibiotic treatment for AGP. Previous antibiotic use was the main modifiable factor. Its presence highlights the importance of avoiding unnecessary antibiotics in order to bring down the high rates of MDR Gram-negative bacilli infections in this population

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia

The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococal pneumonia treated either with β-lactam monotherapy or with combination therapy (β-lactam plus fluoroquinolone). Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10, and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on β-lactam monotherapy were compared with those receiving combination therapy. Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with β-lactam monotherapy and those treated with combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 h (p = 0.016). Our data suggest that systemic expression of IL-6 production in patients with PP correlates with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 h

Risk of acute deterioration and care complexity individual factors associated with health outcomes in hospitalised patients with COVID-19: a multicentre cohort study

Background: Evidence about the impact of systematic nursing surveillance on risk of acute deterioration of patients with COVID-19 and the effects of care complexity factors on inpatient outcomes is scarce. The aim of this study was to determine the association between acute deterioration risk, care complexity factors and unfavourable outcomes in hospitalised patients with COVID-19. Methods: A multicentre cohort study was conducted from 1 to 31 March 2020 at seven hospitals in Catalonia. All adult patients with COVID-19 admitted to hospitals and with a complete minimum data set were recruited retrospectively. Patients were classified based on the presence or absence of a composite unfavourable outcome (in-hospital mortality and adverse events). The main measures included risk of acute deterioration (as measured using the VIDA early warning system) and care complexity factors. All data were obtained blinded from electronic health records. Multivariate logistic analysis was performed to identify the VIDA score and complexity factors associated with unfavourable outcomes. Results: Out of a total of 1176 patients with COVID-19, 506 (43%) experienced an unfavourable outcome during hospitalisation. The frequency of unfavourable outcomes rose with increasing risk of acute deterioration as measured by the VIDA score. Risk factors independently associated with unfavourable outcomes were chronic underlying disease (OR: 1.90, 95% CI 1.32 to 2.72; p<0.001), mental status impairment (OR: 2.31, 95% CI 1.45 to 23.66; p<0.001), length of hospital stay (OR: 1.16, 95% CI 1.11 to 1.21; p<0.001) and high risk of acute deterioration (OR: 4.32, 95% CI 2.83 to 6.60; p<0.001). High-tech hospital admission was a protective factor against unfavourable outcomes (OR: 0.57, 95% CI 0.36 to 0.89; p=0.01). Conclusion: The systematic nursing surveillance of the status and evolution of COVID-19 inpatients, including the careful monitoring of acute deterioration risk and care complexity factors, may help reduce deleterious health outcomes in COVID-19 inpatients

Effect of statin use on outcomes of adults with candidemia

Background: Statins have immunomodulatory properties and hinder Candida growth. However, it is unknown whether they may improve prognosis in patients with candidemia. We sought to determine the effect of prior statin use on the clinical outcomes of patients suffering candidemia. Methods and Findings: Multicenter cohort study of hospitalized adults with candidemia between 2005 and 2011 in six hospitals in Spain, Brazil and Argentina. Of 326 candidemias, 44 (13.5%) occurred in statin users and 282 (86.5%) in statin non-users. The median value of APACHE II at candidemia diagnosis was similar between groups (18 vs. 16; p=.36). Candida albicans was the most commonly isolated species, followed by C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei. There were no differences regarding appropriate empirical antifungal treatment. Statin users had a lower early (5 d) case-fatality rate than non-users (4.5 vs. 17%; p=.031). This effect was not observed with other cardiovascular drugs (aspirin, beta blockers and ACE inhibitors). Independent factor related to early case-fatality rate was APACHE II score (AOR, 1.08; 95% CI, 1.03-1.14; p=.002). An appropriate empirical antifungal therapy (AOR, 0.11; 95% CI, 0.04-0.26; p=<.001) and prior statin use were independently associated with lower early case-fatality (AOR, 0.17; 95% CI, 0.03-0.93; p=.041). Fourteen days (14d) and overall (30d) case-fatality rates were similar between groups (27% vs. 29%; p=0.77 and 40% vs. 44%; p=.66). Conclusions: The use of statins might have a beneficial effect on outcomes of patients with candidemia. This hypothesis deserves further evaluation in randomized trials

Resumen ejecutivo de la Declaración de consenso del Grupo de Estudio de la Infección en el Trasplante (GESITRA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) y la Organización Nacional de Trasplantes (ONT) sobre los criterios de selección de donantes de órganos sólidos en relación con las enfermedades infecciosas

The immunosuppressive treatment that recipients receive from a solid organ transplantation hinders the defensive response to infection. Its transmission from the donor can cause dysfunction or loss of the graft and even death of the recipient if proper preventive measures are not established. This potential risk should be thoroughly evaluated to minimise the risk of infection transmission from donor to recipient, especially with organ transplantation from donors with infections, without increasing graft dysfunction and morbidity and mortality in the recipient. This document aims to review current knowledge about infection screening in potential donors and offer clinical and microbiological recommendations about the use of organs from donors with infection based on available scientific evidence.This work was supported by GESITRA/SEIMC, ONT and‘Plan Nacional de I+D+I’ and Instituto de Salud Carlos III(Fondo de Investigaciones Sanitarias 12/02269 and ProyectoIntegrado de Excelencia 13/00045), Subdirección General de Redesy Centros de Investigacion Cooperativa, Spanish Ministry of Econ-omy and Competitiveness, Spanish Network for Research inInfectious Diseases (REIPI RD16/0016), co-financed by the Euro-pean Development Regional Fund A way to achieve Europe

Characteristics and outcomes by ceiling of care of subjects hospitalized with COVID-19 during four waves of the pandemic in a metropolitan area: a multicenter cohort study

Introduction The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia. Methods Observational study conducted during the first (March–April 2020), second (October–November 2020), third (January–February 2021), and fourth wave (July–August 2021) of COVID-19 in five centers of Catalonia. All subjects were adults (>¿18 years old) hospitalized with a proven SARS-CoV-2 infection and with therapeutic ceiling of care assessed by the attending physician at hospital admission. Results A total of 5813 subjects were analyzed. Subjects with a ceiling of care were mainly older (difference in median age of 20 years), with more comorbidities (Charlson index 3 points higher) and with fewer clinical signs at baseline than patients without a ceiling of care. Some features of their clinical profiles changed among waves. There were differences in treatments received during hospital admission across waves, but not between subjects with and without a ceiling of care. Subjects with a ceiling of care had a death incidence more than four times the death incidence of subjects a without a ceiling of care (risk ratio (RR) ranging from 3.5 in the first wave to almost 6 in the third and fourth). Incidence of severe pneumonia and complications for subjects with a ceiling of care was around 1.5 times the incidence in subjects without a ceiling of care. Discussion Analysis of hospitalized subjects with SARS-CoV-2 infection should be stratified according to therapeutic ceiling of care to avoid bias and outcome misestimation.This study was partially funded by Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya (2020PANDE00148).Peer ReviewedPostprint (published version

Impact of an educational program to reduce healthcare resources in community-acquired pneumonia: The EDUCAP randomized controlled trial

BACKGROUND: Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge. METHODS: A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed. RESULTS: We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003). CONCLUSIONS: The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN39531840

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

[Background] There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection.[Methods] This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed.[Results] Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53).[Conclusions] Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III.Peer reviewe