Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort.

BACKGROUND: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. METHODS: Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. RESULTS: Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. CONCLUSIONS: During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis.

Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients.

PURPOSE: Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. METHODS: We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. RESULTS: Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. CONCLUSION: Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19.

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study.

BACKGROUND: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. METHODS: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. RESULTS: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. CONCLUSIONS: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study.

BACKGROUND: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. METHODS: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero (<1 N1 copies per mL), VIR-N1-Low (1-2747 N1 copies per mL), and VIR-N1-Storm (>2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. FINDINGS: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16-0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26-0·57; p<0·0001, compared with the VIR-N1-Storm group). INTERPRETATION: The presence of a so-called viral storm is associated with increased all-cause death in patients admitted to the intensive care unit with severe COVID-19. Preventing this viral storm could help to reduce poor outcomes. Viral storm could be an enrichment marker for treatment with antivirals or purification devices to remove viral components from the blood. FUNDING: Instituto de Salud Carlos III, Canadian Institutes of Health Research, Li Ka-Shing Foundation, Research Nova Scotia, and European Society of Clinical Microbiology and Infectious Diseases. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

PURPOSE: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. METHODS: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. RESULTS: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65-0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58-0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14-1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61-0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. CONCLUSION: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.

Methodology of a Large Multicenter Observational Study of Patients with COVID-19 in Spanish Intensive Care Units.

INTRODUCTION: The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. METHODS: CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. RESULTS: This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. CONCLUSIONS: We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.

PURPOSE: Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. METHODS: This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. RESULTS: A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p < 0.001). CONCLUSION: Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment.

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study.

BACKGROUND: Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients. METHODS: This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis. RESULTS: We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39-0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16-2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes. CONCLUSIONS: Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients.

BACKGROUND: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. METHODS: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. RESULTS: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). CONCLUSIONS: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.

ICU-Acquired Pneumonia Is Associated with Poor Health Post-COVID-19 Syndrome.

BACKGROUND: Some patients previously presenting with COVID-19 have been reported to develop persistent COVID-19 symptoms. While this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the incidence and factors associated with the characteristics of persistent COVID-19. On the other hand, these patients very often have intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence on poor health post-COVID 19 syndrome in ICU-discharged patients. METHODS: This prospective, multicentre, and observational study was carrid out across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. RESULTS: A total of 1255 ICU patients were scheduled to be followed up at 3 months; however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP). Patients requiring invasive mechanical ventilation had more persistent post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, development of ICUAP, and ARDS were independent factors for persistent poor health post-COVID-19. CONCLUSIONS: Persistent post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay, development of ICUAP, and ARDS all comprised independent factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-COVID-19.

Initial Antifungal Strategy Reduces Mortality in Critically Ill Patients With Candidemia: A Propensity Score-Adjusted Analysis of a Multicenter Study.

OBJECTIVE: The objective of this study was to evaluate the impact of the empirical therapy with fluconazole or an echinocandin on 30- and 90-day mortality in critically ill patients with candidemia. The outcome of patients in whom the empirical echinocandin was deescalated to fluconazole was also assessed. DESIGN: Retrospective, observational multicenter study. SETTING: Medical and surgical ICUs in nine Spanish hospitals. PATIENTS: Adult patients (≥ 18 yr) with an episode of Candida bloodstream infection during ICU admission from January 2011 to April 2016. INTERVENTIONS: Patient characteristics, infection-related variables, therapeutic interventions, and metastatic complications were reviewed. A propensity score-adjusted multivariable analysis was performed to identify the risk factors significantly associated with 30-day and 90-day mortality. MEASUREMENTS AND MAIN RESULTS: A total of 294 patients were diagnosed of candidemia in the participant ICUs. Sixty patients were excluded (other antifungals in the primary therapy or the patient died without empirical antifungal therapy). The study group comprised 115 patients who received fluconazole (30-day mortality, 37.4%) and 119 patients treated empirically with an echinocandin (30-day mortality, 31.9%). The use of an echinocandin in the empirical therapy was a protective factor for 30-day (odds ratio, 0.32; 95% CI, 0.16-0.66; p = 0.002) and 90-day mortality (odds ratio, 0.50; 95% CI, 0.27-0.93; p = 0.014) in the propensity score- adjusted multivariable analysis. Deescalation of the empirical echinocandin to fluconazole was not associated with a higher mortality or the occurrence of long-term complications. CONCLUSIONS: Empirical use of an echinocandin in critically ill patients with documented candidemia reduces mortality at 30 and 90 days significantly. Deescalation of the empirical echinocandin to fluconazole is safe and effective in fluconazole-susceptible infections.

Candida albicans Germ-Tube Antibody: Evaluation of a New Automatic Assay for Diagnosing Invasive Candidiasis in ICU Patients.

Testing for Candida albicans germ-tube antibody IFA IgG assay (CAGTA) is used to detect invasive candidiasis infection. However, most suitable assays lack automation and rapid single-sample testing. The CAGTA assay was adapted in an automatic monotest system (invasive candidiasis [CAGTA] VirClia® IgG monotest (VirClia®), a chemiluminescence assay with ready-to-use reagents that provides a rapid objective result. CAGTA assay was compared with the monotest automatic VirClia® assay in order to establish the diagnostic reliability, accuracy, and usefulness of this method. A prospective study with 361 samples from 179 non-neutropenic critically ill adults patients was conducted, including 21 patients with candidemia, 18 with intra-abdominal candidiasis, 84 with Candida spp. colonization, and 56 with culture-negative samples, as well as samples from ten healthy subjects. Overall agreement between the two assays (CAGTA and VirCLIA) was 85.3%. These assays were compared with the gold-standard method to determine the sensitivity, specificity as well as positive and negative predictive values. In patients with candidemia, values for CAGTA and VirCLIA assays were 76.2 versus 85.7%, 80.3 versus 75.8%, 55.2 versus 52.9%, and 91.4 versus 94.3%, respectively. The corresponding values in patients with intra-abdominal candidiasis were 61.1 versus 66.7%, 80.3 versus 75.8%, 45.8 versus 42.9%, and 88.3 versus 89.3%, respectively. No differences were found according to the species of Candida isolated in culture, except for Candida albicans and C. parapsilosis, for which VirClia® was better than CAGTA. According to these results, the automated VirClia® assay was a reliable, rapid, and very easy to perform technique as tool for the diagnosis invasive candidiasis.

Efficacy and safety of caspofungin in critically ill patients. ProCAS Study

Introducción. Caspofungina es una equinocandina con eficacia probada en candidiasis invasiva (CI) y aspergilosis invasiva (AI). ProCAS es un estudio patrocinado por el Grupo de Trabajo de Enfermedades Infecciosas de la Sociedad Española de Medicina Intensiva Critica Y Unidades Coronarias (Semicyuc), que trata de analizar su efectividad y seguridad en condiciones de práctica clínica habitual en el paciente grave ingresado en UCI. Material y métodos. Estudio observacional, prospectivo y multicéntrico que tiene como objetivo estimar la efectividad clínica y la seguridad del acetato de caspofungina en el tratamiento de CI y de AI en pacientes críticos refractarios o intolerantes al tratamiento antifúngico convencional. La valoración de la efectividad tanto clínica como la microbiológica se realizó al final del tratamiento con caspofungina. Resultados. Se incluyeron 98 pacientes; 62 CI probadas, 25 CI probables y 11 AI probables, procedentes de 24 centros, durante los años 2005 y 2006. El tratamiento con caspofungina se realizó en monoterapia en el 89.8% de los casos y como primera línea en el 54.1%. La respuesta clínica favorable obtenida para CI, CI probable y AI probable fue de 91,9%, 84% y 81.8%, respectivamente. La respuesta microbiológica fue favorable en el 74,6%, 68% y 54.6%, para los casos de CI probada, CI probable y AI probable, respectivamente. No se objetivaron efectos adversos graves. Conclusiones. En condiciones de práctica clínica habitual, caspofungina es eficaz y segura para el tratamiento de infecciones fúngicas invasoras (CI/AI). El perfil de eficacia y seguridad fue similar al observado en los ensayos clínicos publicados(AU)

Introduction. Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). ProCAS is a study sponsored by the Working Group of the Infectious Diseases of the Spanish Society of Intensive Care Medicine, which analyzes the effectiveness and safety of caspofungin in routine clinical practice conditions in the critically ill. Methods. A prospective, multicenter, observational study designed to estimate the clinical effectiveness and safety of caspofungin acetate in the treatment of IC and IA in patients refractory to or intolerant of conventional antifungal therapy. The assessment of effectiveness both clinic and the microbiological was carried out at the end of the treatment with caspofungin. Results. We included 98 patients, 62 IC proven, 25 probable and 11 IA probable, from 24 centers during 2005 and 2006. Treatment with caspofungin monotherapy was performed in 89.8% of cases and as first line therapy in 54.1%. The favorable clinical response obtained for IC, probable IC, and probable IA was 91.9, 84, and 81.8%, respectively. The microbiological response was favorable in 74.6, 68, and 54.6% for proven cases of IC, probable IC, and probable IA, respectively. No serious adverse effects were observed. Conclusions. In routine clinical practice conditions, caspofungin is effective and safe for the treatment of invasive fungal infections (IC/IA). The efficacy and safety profile was similar to that observed in published clinical trials(AU)

Efficacy and safety of caspofungin in critically ill patients. ProCAS Study.

INTRODUCTION: Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). ProCAS is a study sponsored by the Working Group of the Infectious Diseases of the Spanish Society of Intensive Care Medicine, which analyzes the effectiveness and safety of caspofungin in routine clinical practice conditions in the critically ill. METHODS: A prospective, multicenter, observational study designed to estimate the clinical effectiveness and safety of caspofungin acetate in the treatment of IC and IA in patients refractory to or intolerant of conventional antifungal therapy. The assessment of effectiveness both clinic and the microbiological was carried out at the end of the treatment with caspofungin. RESULTS: We included 98 patients, 62 IC proven, 25 probable and 11 IA probable, from 24 centers during 2005 and 2006. Treatment with caspofungin monotherapy was performed in 89.8% of cases and as first line therapy in 54.1%. The favorable clinical response obtained for IC, probable IC, and probable IA was 91.9, 84, and 81.8%, respectively. The microbiological response was favorable in 74.6, 68, and 54.6% for proven cases of IC, probable IC, and probable IA, respectively. No serious adverse effects were observed. CONCLUSIONS: In routine clinical practice conditions, caspofungin is effective and safe for the treatment of invasive fungal infections (IC/IA). The efficacy and safety profile was similar to that observed in published clinical trials.

Papel de daptomicina en el tratamiento empírico y dirigido de infecciones por cocos grampositivos del paciente crítico / Role of daptomycin in the empirical and directed therapy of infections caused by Grampositive bacteria in the critically ill patient

Las infecciones graves causadas por bacterias grampositivas son un problema grave y que se asocia a una elevada mortalidad. Entre ellas, hay que resaltar las causadas por Staphylococcus aureus resistente a meticilina siendo la bacteriemia primaria o asociada a catéter o a endocarditis las principales presentaciones. Vancomicina ha sido tradicionalmente el tratamiento de elección para estas infecciones pero su actividad no es satisfactoria especialmente en caso de SARM con concentración mínima inhibitoria (CMI) > 1mg/L. Daptomicina es un antibiótico lipopéptido cuyo espectro de acción son las bacterias grampositivas incluyendo SARM y Enterococcus spp resistente a glucopéptido. Destacar también que frente a S. aureus sensible a meticilina, daptomicina es rápidamente bactericida y más activo que vancomicina y al menos tan activo como las penicilinas isoxazólicas, En el presente artículo se discute el papel de este antibiótico en el tratamiento empírico y dirigido de las infecciones por bacterias grampositivas que afectan a los pacientes críticos(AU)

Infections caused by Gram-positive bacteria are a serious problem and is associated with high mortality. Among them, we should highlight those caused by methicillin-resistant Staphylococcus aureus (MRSA). Primary bacteremia, catheterrelated bloodstream infections and constitute the main presentations. Vancomycin has traditionally been the treatment of choice for these infections, but its activity is not satisfactory especially in cases of MRSA with minimum inhibitory concentration (MIC) > 1 mg/L. Daptomycin is a lipopeptide antibiotic active against Gram-positive bacteria including MRSA and glycopeptide-resistant Enterococcus spp. It is worth mentioning that daptomycin is rapidly bactericidal against methicillin-sensitive S. aureus, more potent than vancomycin and at least as active as isoxazole penicillins. This article discusses the role of this antibiotic in the empirical treatment of infections and directed by Gram-positive bacteria affecting critically ill patients(AU)

Severe 2009 A/H1N1v influenza in pregnant women in Spain.

OBJECTIVES: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units. DESIGN AND PATIENTS: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units. MAIN RESULTS: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women. CONCLUSIONS: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

Peritonitis candidiásica / Candida peritonitis

Debido a que Candida spp. es un componente de la flora endógena del tubo digestivo, puede formar parte de la etiología de prácticamente cualquier tipo de infección abdominal. Es frecuente, por ello, aislar Candida spp. en las peritonitis secundarias polimicrobianas por dehiscencia de suturas intestinales. En estos casos no hay acuerdo claro acerca de cuando el aislamiento de Candida spp. en drenajes peritoneales representa infección y no colonización. La recomendación general es interpretar que hay infección cuando la muestra en la que se identifica el germen es intraoperatoria o se ha obtenido mediante punción directa de la colección intraabdominal. Cuando se cultiva Candida spp. en las muestras de drenajes tomadas posteriormente es posible que se trate de una simple colonización. Sin embargo, cuando estos cultivos se acompañan de signos de sepsis, el paciente reúne criterios de gravedad o bien se aísla Candida spp. repetidamente, la mayoría de los intensivistas deciden iniciar tratamiento antifúngico. Este tratamiento es similar para candidemias, candidiasis invasivas diseminada y peritonitis candidiásica

Candida spp. is a component of the endogenous flora of the digestive tract and can consequently form part of the etiology of almost any type of abdominal infection. Candida spp. is therefore frequently isolated in polymicrobial secondary peritonitis due to intestinal suture dehiscence. In these cases, there is no clear consensus on when Candida spp. isolation in peritoneal drainage fluid represents infection rather than colonization. The general recommendation is to interpret that there is infection when the sample containing the pathogen is intraoperative or has been obtained directly from the intraabdominal collection. When Candida spp. is cultured in samples from subsequently obtained drainage fluid, colonization is a possibility. However, when these cultures are accompanied by signs of sepsis, the patient shows severity criteria or Candida spp. is repeatedly isolated, most intensivists decide to begin antifungal therapy. This treatment is similar for candidemias, disseminated invasive candidiasis and Candida peritonitis

Uso de los glucocorticoides en el tratamiento del paciente con sepsis grave: ¿otro ejemplo de la ley del péndulo? / Corticosteroids in the treatment of severe sepsis: another example of the swing of the pendulum?

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