Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.

BACKGROUND: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. METHODS: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. RESULTS: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. CONCLUSION: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. TRIAL REGISTRATION: PROSPERO (CRD42019128790).

Impact of Prophylactic Norfloxacin in Multidrug Resistant Bacterial Infections in the Early Liver Posttransplant Period.

OBJECTIVES: Norfloxacin is indicated as primary or secondary prophylaxis for spontaneous bacterial peritonitis in patients with cirrhosis. A history of spontaneous bacterial peritonitis favors colonization by multidrug-resistant bacteria. Infections caused by these bacteria increase morbidity and mortality after transplant. We investigated prophylactic norfloxacin as a risk factor for multidrug-resistant bacterial infections in the early posttransplant period. MATERIALS AND METHODS: This prospective cohort study included all adult liver recipients in 2 centers between 2015 and 2016. Recipients were classified into 2 groups according to whether or not they received prophylactic norfloxacin pretransplant. Data collection from liver recipients included pretransplant and first month after transplant clinical and microbiological data. Demographic and clinical data of corresponding donors were also collected. RESULTS: We included 157 liver recipients: 54 (34.6%) received norfloxacin and 103 (65.6%) did not received norfloxacin. There were 63 postoperative infections in 47 recipients (29.9%); 17/63 (27%) were multidrug- resistant bacterial infections. The urinary tract was the most commonly affected site (10/17 episodes, 58.8%), and Klebsiella pneumoniae was the microorganism most often isolated (8/17, 47.1%). Incidence of multidrug-resistant bacterial infection was higher in the norfloxacin group (22.2% vs 4.9%; relative risk = 5.6, 95% CI, 1.85-16.89; P = .001).This association was significant after controlling for most confounding factors, including pretransplant vasoactive support (P = .03), Model for End-Stage Liver Disease score (P = .01), previous spontaneous bacterial peritonitis (P = .02), chronic renal impairment (P = .005), number of packed red blood cells (P = .004), use of antilymphocyte globulin as induction (P = .006), and hepatocellular carcinoma (P = .02), but not pre- transplant antibiotic treatment (P = .06). CONCLUSIONS: For recipients who have received prophylactic norfloxacin, clinicians should be aware of the high risk of multidrug-resistant bacterial infections during the first month after liver transplant.

Managing the Next Wave of Influenza and/or SARS-CoV-2 in the ICU-Practical Recommendations from an Expert Group for CAPA/IAPA Patients.

The aim of this study was to establish practical recommendations for the diagnosis and treatment of influenza-associated invasive aspergillosis (IAPA) based on the available evidence and experience acquired in the management of patients with COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA/IAPA expert group defined 14 areas in which recommendations would be made. To search for evidence, the PICO strategy was used for both CAPA and IAPA in PubMed, using MeSH terms in combination with free text. Based on the results, each expert developed recommendations for two to three areas that they presented to the rest of the group in various meetings in order to reach consensus. As results, the practical recommendations for the management of CAPA/IAPA patients have been grouped into 12 sections. These recommendations are presented for both entities in the following situations: when to suspect fungal infection; what diagnostic methods are useful to diagnose these two entities; what treatment is recommended; what to do in case of resistance; drug interactions or determination of antifungal levels; how to monitor treatment effectiveness; what action to take in the event of treatment failure; the implications of concomitant corticosteroid administration; indications for the combined use of antifungals; when to withdraw treatment; what to do in case of positive cultures for Aspergillus spp. in a patient with severe viral pneumonia or Aspergillus colonization; and how to position antifungal prophylaxis in these patients. Available evidence to support the practical management of CAPA/IAPA patients is very scarce. Accumulated experience acquired in the management of CAPA patients can be very useful for the management of IAPA patients. The expert group presents eminently practical recommendations for the management of CAPA/IAPA patients.

Pharmacokinetics of cefiderocol during extracorporeal membrane oxygenation: A case report.

Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.

Positive Polymerase Chain Reaction for SARS-CoV-2 in a Candidate Does Not Always Preclude Liver Transplantation: Case Report and Literature Review.

We report a case of a liver transplant performed in a patient with a history of SARS-CoV-2 infection who presented with a positive polymerase chain reaction test for SARS-CoV-2 on the day of transplant. The transplant procedure was performed without complications, and the patient did not develop symptoms after the initiation of immunosuppression. We also reviewed the literature for similar cases. The emergence of SARS-CoV-2 has forced the medical community to continuously adapt protocols to the current situation. Prudence is needed in immuno- compromised patients, and clinical experience is being built day by day. Thus, a positive polymerase chain reaction test for SARS-CoV-2 in a recipient should not always prevent a liver transplant.

Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients (ISASOT Study).

Isavuconazole (ISA) is an alternative treatment for Aspergillus spp. and other fungal infections, but evidence regarding its use in solid organ transplant recipients (SOTR) is scarce. All SOTR who received ISA for treatment of a fungal infection (FI) at our center from December 2017 to January 2021 were included. The duration of the treatment depended on the type of infection. All patients were followed up to 3 months after treatment. Fifty-three SOTR were included, and the majority (44, 83%) were lung transplant recipients. The most frequently treated FI was tracheobronchitis (25, 46.3%). Aspergillus spp. (43, 81.1%); specially A. flavus (16, 37.2%) and A. fumigatus (12, 27.9%), was the most frequent etiology. Other filamentous fungi including one mucormycosis, and four yeast infections were treated. The median duration of treatment was 81 days (IQR 15-197). Mild gamma-glutamyltransferase elevation was the most frequent adverse event (34%). ISA was prematurely discontinued in six patients (11.3%) due to mild hepatotoxicity (2), fatigue (2), gastrointestinal intolerance (1) and myopathy (1). The mean tacrolimus dose decrease was 30% after starting ISA. Seven patients received ISA with mTOR inhibitors with good tolerability. Two patients developed breakthrough FI (3.8%). Among patients who completed the treatment, 27 (50.9%) showed clinical cure and 15 (34.1%) presented fungal persistence. Three patients (6%) died while on ISA due to FI. ISA was well tolerated and appeared to be an effective treatment for FI in SOTR. IMPORTANCE We describe 53 solid organ transplant recipients treated with isavuconazole for fungal infections. Because its use in clinical practice, there is scarce data of its use in solid organ transplant recipients, where interactions with calcineurin inhibitors and mTOR and adverse drug events have limited the use of other triazoles. To the best of our knowledge, this is the first article describing the safety regarding adverse events and drug interactions of isavuconazole for the treatment of fungal infections in a cohort of solid organ transplant recipients. Also, although this is a noncomparative study, we report some real world effectivity data of these patients, including treatment of non-Aspergillus fungal infections.

Organización de la atención a pacientes críticos en situación de pandemia: Experiencia del Hospital Vall d’Hebron durante el brote de neumonía por SARS-CoV-2 / Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d’Hebron University Hospital

IntroducciónEn un escenario de circulación comunitaria del virus, el impacto de la pandemia sobre el sistema sanitario y en las unidades de cuidados intensivos (UCI) se preveía devastador. El Hospital Universitario Vall d’Hebron (HUVH) ha desplegado un dispositivo de atención a pacientes críticos sin precedentes.MétodosSe describen las previsiones realizadas, las medidas tomadas y los principales resultados en una cohorte de pacientes críticos durante los primeros dos meses (3 de marzo al 2 de mayo del 2020) de la pandemia por COVID-19 en el HUVH de Barcelona.ResultadosEn el periodo de estudio, ingresaron en las Unidades de Críticos del HUVH 333 pacientes. El porcentaje de los pacientes en VMI o VMI y ECMO se mantuvo constantemente por encima del 78%. La mayoría de pacientes han sido hombres (65%); el grupo de edad más frecuente entre 60 y 70 años. Veintitrés pacientes recibieron ECMO, 18 de los cuales fueron canulados en otro centro y trasladados al HUVH. A fecha de cierre del estudio, 14 pacientes se decanularon satisfactoriamente, tres pacientes fallecieron y el resto siguen en soporte con ECMO. Han sido atendidas en UCI ocho gestantes, con una supervivencia del 100%. La mortalidad en UCI de los pacientes menores de 60 años fue el 3,2%. La estancia media en UCI de las altas y los fallecimientos ha sido de 14 días.ConclusionesLas estrategias de organización de la expansión de recursos para la atención de pacientes críticos, sus principales retos y los resultados obtenidos, pueden servir de clave para futuros escenarios similares.

IntroductionIn the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d́Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources.MethodsWe describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona.In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained.ResultsThree-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days.ConclusionThe adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios.

Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d'Hebron University Hospital.

INTRODUCTION: In the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d'Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources. METHODS: We describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona. In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained. RESULTS: Three-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days. CONCLUSION: The adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios.

Mortality Following Clostridioides difficile Infection in Europe: A Retrospective Multicenter Case-Control Study.

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were ß-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome.

Does Routine Abdominal Drain Tip Culture Anticipate Post-Operative Infection in Liver Transplantation?

Background: Bacterial infections are a common complication after liver transplantation. Usually, abdominal drains are placed at the end of the surgical procedure. The usefulness of routine drain tip culture has not been investigated. Patients and Methods: This retrospective study included 200 liver transplants between 2010 and 2015. We excluded patients without drain tip culture and those with abdominal or systemic complications before removal of drains. Demographic, clinical (pre-transplant, peri-operative and post-transplant) and microbiologic information were collected up to 30 days after operation. Three-month survival and re-transplantation were recorded. Results: There were 94 patients included. Drain tip culture was positive in 78 (83%) patients. The most common isolates were coagulase-negative staphylococci (30.9%), mixed gram-positive cocci (13.8%), and polymicrobial (21.3%). In 26 patients, 35 post-operative infections developed, with no differences between recipients with and without positive drain tip culture (22.8% vs. 25%; p > 0.99). In two patients, Staphylococcus aureus was isolated in drain tip cultures and in cultures confirming the post-operative infection (one catheter-related bacteremia and one drain-related peritonitis). In two other recipients, the positive drain tip culture had an impact on clinical management. All patients survived. Conclusions: Routine drain tip culture in asymptomatic liver recipients seems unhelpful. It may be more reasonable to perform it only in patients with suspicion of complications.

Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d'Hebron University Hospital. / Organización de la atención a pacientes críticos en situación de pandemia: Experiencia del Hospital Vall d'Hebron durante el brote de neumonía por SARS-CoV-2.

INTRODUCTION: In the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d́Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources. METHODS: We describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona. In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained. RESULTS: Three-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days. CONCLUSION: The adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios.

Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review.

The endothelial glycocalyx comprises a complex layer of membrane-bound proteoglycans, secreted glycosaminoglycans, glycoproteins, glycolipids and bound plasma proteins such as albumin and antithrombin associated with the endothelial surface. The glycocalyx plays an important role in vascular homeostasis, regulating vascular permeability and cell adhesion, and acts as a mechanosensor for hemodynamic shear stresses; it also has antithrombotic and anti-inflammatory functions. Plasma proteins such as albumin are physiologically bound within the glycocalyx, thus contributing to stability of the layer. Albumin is the major determinant of plasma colloid osmotic pressure. In addition, albumin transports sphingosine-1-phosphate which has protective endothelial effects, acts as a free radical scavenger, and has immunomodulatory and anti-inflammatory effects. This review examines the physiological function of the endothelial glycocalyx and the role of human albumin in preserving glycocalyx integrity and the microcirculation.

Routine Bile Culture From Liver Donors as Screening of Donor-Transmitted Infections in Liver Transplantation.

Bacterial infections are an important threat in the early post-liver transplantation period. Donor-transmitted infections, although rare, can have high mortality. The utility of routine culture from the donor bile duct as screening of donor-transmitted infection has not been evaluated. We performed a retrospective study of 200 consecutive liver transplants between 2010 and 2015. Demographic, clinical, and microbiological data were collected from the recipients' medical records. Clinical data included pretransplantation, perioperative, and posttransplantation information (until 30 days after the procedure). The 3-month patient survival and/or retransplantation were recorded. A total of 157 samples from the donor bile duct were collected and cultured. Only 8 were positive. The microorganisms isolated were as follows: Klebsiella pneumoniae, n = 2; Escherichia coli, n = 1; Enterobacter cloacae, n = 1; Streptococcus anginosus, n = 1; Streptococcus sp., n = 1; multiple gram-negative bacilli, n = 1; and polymicrobial, n = 1. All of the microorganisms were susceptible to the antibiotic prophylaxis administered. During the first month after transplantation, 81 recipients developed 131 infections. Only 1 of these recipients had a donor with a positive bile culture, and none of the infections were due to the microorganism isolated in the donor's bile. The 3-month overall survival was 89.5%, and there were no differences between recipients with positive donor bile cultures and those with negative donor bile cultures (87.5% versus 89.26%; P > 0.99). Routine testing of donor bile cultures does not predict recipients' infection or survival after liver transplantation and should not be recommended.

Effects of the extracorporeal membrane oxygenation circuit on plasma levels of ceftolozane.

INTRODUCTION: New antibiotics with bactericidal activity against multi-drug-resistant bacteria are increasingly used in the intensive care units. Here, we aimed to evaluate the influence of the extracorporeal membrane oxygenation on plasma levels of ceftolozane. CASE REPORT: A 34-year-old female was admitted to the intensive care unit after bilateral lung transplantation, complicated by primary graft dysfunction and cardiogenic shock needing venoarterial extracorporeal membrane oxygenation. Ceftolozane/tazobactam was started. Plasma ceftolozane levels were monitored on the first and third days of antibiotic treatment. A non-compartment pharmacokinetic analysis was performed and the extraction rate through the oxygenator was calculated. DISCUSSION: The extracorporeal circuit of extracorporeal membrane oxygenation may alter the pharmacokinetics of antibiotics, to varying degrees due to drug sequestration and increased distribution volume. In this case, the extracorporeal membrane oxygenation circuit had little impact on the ceftolozane plasma concentration. CONCLUSION: Plasma levels of ceftolozane are stable in the extracorporeal membrane oxygenation circuit, suggesting that adjustment of standard doses of ceftolozane in patients with extracorporeal membrane oxygenation support may not be needed.

Donor-derived bacterial infections in lung transplant recipients in the era of multidrug resistance.

OBJECTIVES: Our aim was to analyze the prevalence of multidrug-resistant bacterial infections in lung transplant donors and to evaluate its influence on donor-derived bacterial infections. METHODS: We conducted a retrospective study of adult patients who underwent lung transplantation (2013-2016) at our hospital. Donor-derived bacterial infection was defined as the isolation of the same bacteria with identical antibiotic susceptibility patterns in the recipient and the perioperative cultures from the donor during the first month posttransplantation. We utilized a preventive antibiotic strategy adapted to the bacteria identified in donor cultures using systemic and nebulized antibiotics. RESULTS: 252 lung transplant recipients and 243 donors were included. In 138/243 (56.8%) donors, one bacterial species was isolated from at least one sample; graft colonization (118/243; 48.6%), blood cultures (5/243; 2.1%) and the contamination of preservation fluids (56/243; 23%). Multidrug-resistant bacteria were isolated from 12/243 (4.9%) donors; four Enterobacterales, four Stenotrophomonas maltophilia, three Pseudomonas aeruginosa and one methicillin-resistant Staphylococcus aureus. There was no transmission of these multidrug-resistant bacteria. Donor-derived infections, primarily tracheobronchitis due to non-MDR bacteria, were diagnosed in 7/253 (2.9%) recipients, with good clinical outcomes. CONCLUSIONS: The lungs of donors colonized with multidrug-resistant bacteria may be safely used when recipients receive prompt tailored antibiotic treatment.

Organización de la atención a pacientes críticos en situación de pandemia: Experiencia del Hospital Vall d'Hebron durante el brote de neumonía por SARS-CoV-2 / Planning for the assistance of critically ill patients in a Pandemic Situation: The experience of Vall d'Hebron University Hospital

INTRODUCCIÓN: En un escenario de circulación comunitaria del virus, el impacto de la pandemia sobre el sistema sanitario y en las unidades de cuidados intensivos (UCI) se preveía devastador. El Hospital Universitario Vall d'Hebron (HUVH) ha desplegado un dispositivo de atención a pacientes críticos sin precedentes. MÉTODOS: Se describen las previsiones realizadas, las medidas tomadas y los principales resultados en una cohorte de pacientes críticos durante los primeros dos meses (3 de marzo al 2 de mayo del 2020) de la pandemia por COVID-19 en el HUVH de Barcelona. RESULTADOS: En el periodo de estudio, ingresaron en las Unidades de Críticos del HUVH 333 pacientes. El porcentaje de los pacientes en VMI o VMI y ECMO se mantuvo constantemente por encima del 78%. La mayoría de pacientes han sido hombres (65%); el grupo de edad más frecuente entre 60 y 70 años. Veintitrés pacientes recibieron ECMO, 18 de los cuales fueron canulados en otro centro y trasladados al HUVH. A fecha de cierre del estudio, 14 pacientes se decanularon satisfactoriamente, tres pacientes fallecieron y el resto siguen en soporte con ECMO. Han sido atendidas en UCI ocho gestantes, con una supervivencia del 100%. La mortalidad en UCI de los pacientes menores de 60 años fue el 3,2%. La estancia media en UCI de las altas y los fallecimientos ha sido de 14 días. CONCLUSIONES: Las estrategias de organización de la expansión de recursos para la atención de pacientes críticos, sus principales retos y los resultados obtenidos, pueden servir de clave para futuros escenarios similares

INTRODUCTION: In the context of community transmission of the virus, the impact of the pandemic on health-care systems, mainly on intensive care units (ICU), was expected to be devastating. Vall d'Hebron University Hospital (HUVH) implemented an unprecedented critical patient-care planning and management of resources. METHODS: We describe a cohort of critically ill patients during the first two months of the pandemic (from March 3, 2020, to May 2, 2020) in HUVH, Barcelona. In this manuscript, we report our previsions, strategies implemented, and the outcomes obtained. RESULTS: Three-thousand and thirty-three patients were admitted to the HUVH Critical Care Units. Throughout the study period, the proportion of patients on IMV or IMV and ECMO remained above 78%. Most patients were men (65%); the most common age group was 60-70 years. Twenty-three patients received ECMO, and eighteen were cannulated at another center and transferred to HUVH. At the end of the study, fourteen patients were successfully decannulated, three patients died, and the rest of the patients were still on ECMO. Eight pregnant women have been treated in the ICU, with a survival rate of 100%. The ICU mortality of patients younger than 60 years was 3.2%. The mean ICU stay of both survivors and nonsurvivors was 14 days. CONCLUSION: The adequate preparation for resource expansion for critically ill patients care, main challenges, and overall positive results can serve as a precedent for similar future scenarios

Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients With Lower Respiratory Tract Infections Caused by Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa Treated With Ceftolozane/Tazobactam.

BACKGROUND: Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50% ƒT > minimal inhibitory concentration [MIC]) in plasma and epithelial lining fluid against C/T-susceptible P. aeruginosa. The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR-P. aeruginosa considering the C/T MIC. METHODS: This was a multicenter retrospective study of 90 patients with LRI caused by resistant P. aeruginosa who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality. RESULTS: The median age (interquartile range) was 65 (51-74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5-4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with P. aeruginosa strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%; P = .041). Multivariate analysis identified septic shock (P < .001), C/T MIC >2 mg/L (P = .045), and increasing Charlson Comorbidity Index (P = .019) as independent predictors of mortality. CONCLUSIONS: The effectiveness of C/T in P. aeruginosa LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.

Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults.

BACKGROUND: The definition of sepsis has evolved over time, along with the clinical and scientific knowledge behind it. For years, sepsis was defined as a systemic inflammatory response syndrome (SIRS) in the presence of a documented or suspected infection. At present, sepsis is defined as a life-threatening organ dysfunction resulting from a dysregulated host response to infection. Even though sepsis is one of the leading causes of mortality in critically ill patients, and the World Health Organization (WHO) recognizes it as a healthcare priority, it still lacks an accurate diagnostic test. Determining the accuracy of interleukin-6 (IL-6) concentrations in plasma, which is proposed as a new biomarker for the diagnosis of sepsis, might be helpful to provide adequate and timely management of critically ill patients, and thus reduce the morbidity and mortality associated with this condition. OBJECTIVES: To determine the diagnostic accuracy of plasma interleukin-6 (IL-6) concentration for the diagnosis of bacterial sepsis in critically ill adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and Web of Science on 25 January 2019. We screened references in the included studies to identify additional studies. We did not apply any language restriction to the electronic searches. SELECTION CRITERIA: We included diagnostic accuracy studies enrolling critically ill adults aged 18 years or older under suspicion of sepsis during their hospitalization, where IL-6 concentrations were evaluated by serological measurement. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and extracted data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity using the HSROC model parameters. We conducted all analyses in the SAS statistical software package and R software. MAIN RESULTS: We included 23 studies (n = 4192) assessing the accuracy of IL-6 for the diagnosis of sepsis in critically ill adults. Twenty studies that were available as conference proceedings only are awaiting classification. The included participants were heterogeneous in terms of their distribution of age, gender, main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and origin of infection, among other factors. Prevalence of sepsis greatly varied across studies, ranging from 12% to 78%. We considered all studies to be at high risk of bias due to issues related to the index test domain in QUADAS-2. The SROC curve showed a great dispersion in individual studies accuracy estimates (21 studies, 3650 adult patients), therefore the considerable heterogeneity in the collected data prevented us from calculating formal accuracy estimates. Using a fixed prevalence of sepsis of 50% and a fixed specificity of 74%, we found a sensitivity of 66% (95% confidence interval 60 to 72). If we test a cohort 1000 adult patients under suspicion of sepsis with IL-6, we will find that 330 patients would receive appropriate and timely antibiotic therapy, while 130 patients would be wrongly considered to have sepsis. In addition, 370 out of 1000 patients would avoid unnecessary antibiotic therapy, and 170 patients would have been undiagnosed of sepsis. This numerical approach should be interpreted with caution due to the limitations described above. AUTHORS' CONCLUSIONS: Our evidence assessment of plasma interleukin-6 concentrations for the diagnosis of sepsis in critically ill adults reveals several limitations. High heterogeneity of collected evidence regarding the main diagnosis, setting, country, positivity threshold, sepsis criteria, year of publication, and the origin of infection, among other factors, along with the potential number of misclassifications, remain significant constraints for its implementation. The 20 conference proceedings assessed as studies awaiting classification may alter the conclusions of the review once they are fully published and evaluated. Further studies about the accuracy of interleukin-6 for the diagnosis of sepsis in adults that apply rigorous methodology for conducting diagnostic test accuracy studies are needed. The conclusions of the review will likely change once the 20 studies pending publication are fully published and included.