Current treatment of nosocomial pneumonia and ventilator-associated pneumonia

Nosocomial pneumonia; Treatment; Ventilator-associated pneumoniaPneumònia nosocomial; Tractament; Pneumònia associada al ventiladorNeumonía nosocomial; Tratamiento; Neumonía asociada al ventiladorHospital-acquired pneumonia and ventilator-associated pneumonia are severe nosocomial infections leading to high morbidity and mortality. Broad-spectrum antibiotics with coverage against all likely pathogens are recommended by the international guidelines. Inappropriate empirical treatment is one of the most important prognostic factors. Knowledge of local epidemiology and continuous microbiological surveillance is crucial for improving clinical approaches to empirical antimicrobial treatment. The development of protocols and policies for training healthcare professionals on preventive strategies, such as the "Pneumonia Zero" project, and improved implementation of antimicrobial stewardship practices, will aid early de-escalation of antibiotics and prevent resistance

Risk factors and outcomes of ventilator-associated pneumonia in COVID-19 patients: a propensity score matched analysis

Mortalitat; Pneumònia associada a la ventilació mecànica; COVID-19Mortalidad; Neumonía asociada a la ventilación mecánica; COVID-19Mortality; Ventilator-associated pneumonia; COVID-1

The Use of CytoSorb Therapy in Critically Ill COVID-19 Patients: Review of the Rationale and Current Clinical Experiences

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Teràpia CytoSorbCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Terapia; CytoSorbCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; CytoSorb; TherapyThe COVID-19 pandemic has led to the biggest global health crisis of our lifetime. There is accumulating evidence that a substantial number of critically ill COVID-19 patients exhibit a dysregulated host response manifesting as cytokine storm or cytokine release syndrome, which in turn contributes to the high observed rates of mortality. Just as in other hyperinflammatory conditions, extracorporeal cytokine removal may have potential beneficial effects in this subgroup of COVID-19 patients. The CytoSorb blood purification device is the most extensively investigated cytokine removal platform with considerable evidence suggesting that early intervention can provide rapid hemodynamic stabilization and improvement in vital organ functions. The purpose of this review is to provide an overview of the pathophysiological background of hyperinflammation in COVID-19 and to summarize the currently available evidence on the effects of hemoadsorption in these patients

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain

Carbapenemasa; Infeccions gramnegatives; Infeccions associades a l'assistència sanitàriaCarbapenemasa; Infecciones gramnegativas; Infecciones asociadas a la asistencia sanitariaCarbapenemase; Gram-negative infections; Healthcare-associated infectionsIntroduction. Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. Methods. The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. Results. In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. Conclusion. Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Polymerase Chain Reaction Versus Blood Culture to Detect Candida Species in High-Risk Patients with Suspected Invasive Candidiasis: The MICAFEM Study

Abdominal fluid; Blood cultures; CandidaFluid abdominal; Hemocultiu; CandidaFluido abdominal; Hemocultivo; CandidaWe evaluated the diagnostic reliability of serum polymerase chain reaction (PCR) versus blood culture, abdominal fluid or both (composite measure) in patients receiving empirical antifungal treatment for suspected invasive candidiasis. METHODS: This observational, prospective, non-interventional, multicentre study in Spain enrolled 176 critically ill patients admitted to the intensive care unit. Separate blood samples for culture and serum PCR were taken before the start of antifungal therapy. Patient assessment was performed according to each site's usual clinical practice. The primary end point was concordance between serum PCR and blood culture. Secondary end points were concordance between serum PCR and a positive abdominal fluid sample or the composite measure. Quality indices included sensitivity, specificity, positive/negative predictive values (PPV/NPV) and kappa indices. RESULTS: Among 175 evaluable patients, rates of Candida detection were similar for serum PCR (n = 16/175, 9.1%) versus blood culture (n = 14/175, 8.0%). Quality indices for serum PCR relative to blood culture were: sensitivity 21.4%; specificity 91.9%; PPV 18.8%; NPV 93.1%; kappa index 0.125. Thirty-two abdominal fluid samples were positive. Quality indices for serum PCR versus abdominal fluid were: sensitivity 31.3%; specificity 83.0%; PPV 15.6%; NPV 92.3%; kappa index 0.100. Quality indices for serum PCR versus the composite measure were: sensitivity 15.8%; specificity 92.7%; PPV 37.5%; NPV 79.9%; kappa index 0.107. CONCLUSION: The sensitivity of serum PCR for Candida detection was low and the rate of concordance was low between serum PCR and the other diagnostic techniques used to identify Candida infections. Hospital-based diagnostic tests need optimising to improve outcomes in patients with suspected invasive candidiasis.123/Astellas Pharma Global Developmen

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial

Col·loides; Gelatina; SèpsiaColoides; Gelatina; SepticemiaColloids; Gelatine; SepsisBackground Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. Methods This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. Discussion This study aims to generate evidence regarding which regimen—a gelatine-crystalloid regimen or a pure crystalloid regimen—is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload.In this clinical study, B. Braun Melsungen AG, Carl-Braun Str. 1, D-34212 Melsungen acts as the sponsor, funder and data holder of this study. Additionally, it is the manufacturer of IMP, as well as the co-author and medical writer of this manuscript. B. Braun Melsungen AG organized protocol development and contracted a contract research organization (CRO) for clinical trial application, monitoring, and collection/analysis of study data. Investigational tests and reference products will be produced and delivered by B. Braun Melsungen AG to all participating sites. Open Access funding enabled and organized by Projekt DEAL

Hemoadsorption for severe MIS-C in critically ill children, should we consider it as a therapeutic opportunity?

Coronavirus; Multisystem inflammatory syndrome in children; Pediatric critical careCoronavirus; Síndrome inflamatorio multisistémico en niños; Cuidados críticos pediátricosCoronavirus; Síndrome inflamatòria multisistèmica en nens; Cures crítiques pediàtriquesMultisystem inflammatory syndrome (MIS-C) is a new severe clinical condition that has emerged during the COVID-19 pandemic. MIS-C affects children and the young usually after a mild or asymptomatic COVID-19 infection. MIS-C has a high tropism for the cardiovascular system with need for inotropes and vasopressor support in 62% of cases. As of today a mortality from 1.5% to 1.9% related to MIS-C is reported. Hemoadsorption via the inflammatory mediator adsorber CytoSorb (CytoSorbents Europe, Berlin Germany) has been used as adjunctive therapy with the aim to restore the host response in septic shock and other hyper-inflammatory syndromes. We present the clinical experience of an adolescent boy with a refractory shock secondary to left ventricular dysfunction (LVD) in the context of MIS-C, treated with hemoadsorption, and continuous kidney replacement therapy (CKRT) in combination with immunomodulatory therapies. The therapeutic strategy resulted in hemodynamic and clinical stabilization as well as control of the hyperinflammatory response. Treatment appeared to be safe and feasible. Our findings are in line with previously published clinical cases on Cytosorb use in MIS-C showing the beneficial role of the hemoperfusion with Cytosorb in severe MIS-C to manage the cytokine storm. We provide an analysis and comparison of recent evidence on the use of hemoadsorption as an adjuvant therapy in critically ill children with severe forms of MIS-C, suggesting this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygentation (ECMO) and other mechanical cardiocirculatory supports

Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge

Model animal; COVID-19; Recerca preclínicaModelo animal; COVID-19; Investigación preclínicaAnimal model; COVID-19; Pre-clinical researchMany milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal

Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: a descriptive analysis of the Eurobact II study

Bloodstream infection; COVID-19; EnterococcusInfección del torrente sanguíneo; COVID-19; EnterococoInfecció del torrent sanguini; COVID-19; EnterococBackground The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019.Research grants were obtained from the European society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study Group for Infections in Critically Ill Patients (ESGCIP), the Norva Dahlia foundation and the Redcliffe Hospital Private Practice Trust Fund. Dr. Buetti received a grant from the Swiss National Science Foundation (Grant Number: P4P4PM_194449). The study was endorsed by the critically ill group of the ESCMID (ESGCIP) and by the infection group of the ESICM with scientific input of the OUTCOMEREA network