Post-operative sepsis-induced acute respiratory distress syndrome: risk factors for a life-threatening complication.

Introduction: Prevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis and major surgery are conditions associated with ARDS. We aimed to examine the impact of post-operative sepsis-induced ARDS on 60-day mortality. Methods: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups depending on whether they met criteria for ARDS. Primary outcome was 60-day mortality of post-operative sepsis-induced ARDS. Secondary outcome measures were potential risk factors for post-operative sepsis-induced ARDS, and for 60-day mortality. Results: Higher SOFA score (OR 1.1, 95% CI 1.0-1.3, p = 0.020) and higher lactate (OR 1.9, 95% CI 1.2-2.7, p = 0.004) at study inclusion were independently associated with ARDS. ARDS patients (n = 45) had higher ICU stay [14 (18) vs. 5 (11) days, p < 0.001] and longer need for mechanical ventilation [6 (14) vs. 1 (5) days, p < 0.001] than non-ARDS patients (n = 409). Sixty-day mortality was higher in ARDS patients (OR 2.7, 95% CI 1.1-6.3, p = 0.024). Chronic renal failure (OR 4.0, 95% CI 1.2-13.7, p = 0.026), elevated lactate dehydrogenase (OR 1.7, 95% CI 1.1-2.7, p = 0.015) and higher APACHE II score (OR 2.7, 95% CI 1.3-5.4, p = 0.006) were independently associated with 60-day mortality. Conclusion: Post-operative sepsis-induced ARDS is associated with higher 60-day mortality compared to non-ARDS post-operative septic patients. Post-operative septic patients with higher severity of illness have a greater risk of ARDS and worse outcomes. Further investigation is needed in post-operative sepsis-induced ARDS to prevent ARDS.

Influence of Renal Dysfunction on the Differential Behaviour of Procalcitonin for the Diagnosis of Postoperative Infection in Cardiac Surgery.

Background: procalcitonin is a valuable marker in the diagnosis of bacterial infections; however, the impairment of renal function can influence its diagnostic precision. The objective of this study is to evaluate the differential behaviour of procalcitonin, as well as its usefulness in the diagnosis of postoperative pulmonary infection after cardiac surgery, depending on the presence or absence of impaired renal function. Materials and methods: A total of 805 adult patients undergoing cardiac surgery with extracorporeal circulation (CBP) were prospectively recruited, comparing the behaviour of biomarkers between the groups with and without postoperative pneumonia and according to the presence or absence of renal dysfunction. Results: Pulmonary infection was diagnosed in 42 patients (5.21%). In total, 228 patients (28.32%) presented postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, even in the presence of renal dysfunction. The optimal procalcitonin threshold differed markedly in patients with renal dysfunction compared to patients without renal dysfunction (1 vs. 0.78 ng/mL p < 0.05). The diagnostic accuracy of procalcitonin increased significantly when the procalcitonin threshold was adapted to renal function. Conclusions: Procalcitonin is an accurate marker of postoperative infection in cardiac surgery, even in the presence of renal dysfunction. Renal function is an important determinant of procalcitonin levels and, therefore, its diagnostic thresholds must be adapted in the presence of renal dysfunction.

PCR-based diagnosis of respiratory virus in postsurgical septic patients: A preliminary study before SARS-CoV-2 pandemic.

Respiratory viruses are part of the normal microbiota of the respiratory tract, which sometimes cause infection with/without respiratory insufficiency and the need for hospital or ICU admission. The aim of this study is to determine the prevalence of respiratory viruses in nontransplanted postoperative septic patients as well as lymphocyte count influence in their presence and its relationship to mortality. 223 nontransplanted postsurgical septic patients were recruited on the Intensive Care Unit (ICU) at Hospital Clínico Universitario de Valladolid prior to the SARS-COV-2 pandemic. Patients were split into 2 groups according to the presence/absence of respiratory viruses. Multivariate logistic regression analysis was used to identify independent factors related to positive respiratory virus PCR test. Respiratory viruses were isolated in 28.7% of patients. 28-day mortality was not significantly different between virus-positive and virus-negative groups. Logistic regression analysis revealed that lymphocyte count ≤ 928/µl is independently associated with a positive PCR result [OR 3.76, 95% CI (1.71-8.26), P = .001] adjusted by platelet count over 128,500/µL [OR 4.27, 95% CI (1.92-9.50) P < .001] and the presence of hypertension [OR 2.69, 95% CI (1.13-6.36) P = .025] as confounding variables. Respiratory viruses' detection by using PCR in respiratory samples of nontransplanted postoperative septic patients is frequent. These preliminary results revealed that the presence of lymphopenia on sepsis diagnosis is independently associated to a positive virus result, which is not related to a higher 28-day mortality.

Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality.

BACKGROUND: Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. METHODS: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. RESULTS: In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39-0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. CONCLUSIONS: Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

CEACAM7 polymorphisms predict genetic predisposition to mortality in post-surgical septic shock patients.

We carried out a retrospective exploratory study on 173 patients who underwent major surgery and developed septic shock after surgery. Our findings suggest that CEACAM7 rs1001578, rs10409040, and rs889365 polymorphisms could influence septic shock-related death in individuals who underwent major surgery.

Impact of the Economic Crisis on Endocarditis Mortality in Spain: A Nationwide Study.

Economic recession has dire consequences on overall health. None have explored the impact of economic crisis (EC) on infective endocarditis (IE) mortality. We conducted a retrospective, nationwide, temporal trend study analyzing mortality trends by age, sex, and adverse outcomes in patients diagnosed with IE in Spain from 1997 to 2014. Data were divided into two subperiods: pre-EC (January 1997-August 2008) and post-EC (September 2008-December 2014). A total of 25 952 patients presented with IE. The incidence increased from 301.4 to 365.1 per 10 000 000 habitants, and the mortality rate rose from 24.3% to 28.4%. Those aged >75 years experienced more adverse outcomes. Complications due to sepsis, shock, acute kidney injury requiring dialysis, and heart failure increased after the EC onset, and expenditures soared to €16 216. Expenditure per community was related to mortality (P < .001). The EC resulted as an independent predictor for mortality (hazard ratio 1.06; 95% confidence interval 1.01-1.11). Incidence and mortality rate in patients with IE after the onset of the EC have increased as a result of rising adverse outcomes despite an overall increased investment.

Lipid peroxidation as a hallmark of severity in COVID-19 patients.

BACKGROUND: Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease. METHODS: Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test. RESULTS: Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules' levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 µM) as an independent risk factor for 28-day intubation/death in COVID-19 patients [OR: 2.57; 95% CI: 1.10-5.99; p = 0.029]. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 µM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p < 0.001). CONCLUSION: These findings deepen our knowledge of oxidative stress status in SARS-CoV-2 infection, supporting its important role in COVID-19. In fact, higher lipid peroxidation levels are independently associated to a higher risk of intubation or death at 28 days in COVID-19 patients.

Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles.

Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients. METHODS: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0. RESULTS: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI-(1.28-42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results. CONCLUSIONS: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.

Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can.

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection.

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery-validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines' quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933-0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127-80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846-0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover-validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.

Distinguishing septic shock from non-septic shock in postsurgical patients using gene expression.

OBJECTIVES: To obtain a gene expression signature to distinguish between septic shock and non-septic shock in postoperative patients, since patients with both conditions show similar signs and symptoms. METHODS: Differentially expressed genes were selected by microarray analysis in the discovery cohort. These genes were evaluated by quantitative real time polymerase chain reactions in the validation cohort to determine their reliability and predictive capacity by receiver operating characteristic curve analysis. RESULTS: Differentially expressed genes selected were IGHG1, IL1R2, LCN2, LTF, MMP8, and OLFM4. The multivariate regression model for gene expression presented an area under the curve value of 0.922. These genes were able to discern between both shock conditions better than other biomarkers used for diagnosis of these conditions, such as procalcitonin (0.589), C-reactive protein (0.705), or neutrophils (0.605). CONCLUSIONS: Gene expression patterns provided a robust tool to distinguish septic shock from non-septic shock postsurgical patients and shows the potential to provide an immediate and specific treatment, avoiding the unnecessary use of broad-spectrum antibiotics and the development of antimicrobial resistance, secondary infections and increase health care costs.

HGF, IL-1α, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients.

Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95-6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07-1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39-0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.

OLFM4 polymorphisms predict septic shock survival after major surgery.

BACKGROUND: Higher expression of olfactomedin-4 (OLFM4), a gene regulated by nuclear factor-kappa B (NF-κB), has been related to a higher risk of organ failure and death in patients with septic shock. We aimed to evaluate the association between OLFM4 single nucleotide polymorphisms (SNPs) and septic shock-related death in 175 patients who underwent major surgery, as well as its performance in predicting mortality. MATERIALS AND METHODS: We carried out a retrospective study. A total of seven OLFM4 SNPs were genotyped by Agena Bioscience's MassARRAY platform. Statistical analysis was performed by Kaplan-Meier and Cox regression tests. The diagnostic performance for predicting septic shock-related death was evaluated by the area under the receiver-operating characteristic (AUROC) curve. RESULTS: Patients with rs17552047 A allele and rs1891944 TT genotype had higher survival than patients with rs17552047 G allele (P-value = .024) and patients with rs1891944 CC/CT genotype (P-value = .038). However, only rs17552047 was associated with a lower risk of death under an additive inheritance model (adjusted hazard ratio [aHR] = 0.44, 95% CI = 0.27-0.71). The multivariate model with the most significant clinical variables (lactate, chronic kidney disease, peritonitis, heart disease and elective surgery) showed an AUROC of 0.776 for predicting septic shock-related death. When we added the OLFM4 rs17552047 SNP to the previous model, the AUROC was 0.811 and was close to reaching significant differences with the previous model (P-value = .065). CONCLUSION: OLFM4 rs17552047 A allele predicts septic shock survival in patients who underwent major surgery. Furthermore, rs17552047, together with clinical variables, could be useful to predict the outcome of septic shock.

Impact of nosocomial infections on patient mortality following cardiac surgery.

STUDY OBJECTIVE: To determine the rate of nosocomial infection among patients undergoing cardiac surgery and to identify risk factors and the impact of these infections on patient mortality. DESIGN: Prospective observational study. SETTING: Intensive Care Unit (ICU). PATIENTS: 1097 adult patients who underwent cardiac surgery at Hospital Clínico Universitario de Valladolid between January 2011 and January 2016. INTERVENTIONS: None. MEASUREMENTS: Preoperative, intraoperative and postoperative medical, surgical and anaesthetic variables. MAIN RESULTS: A total of 111 patients (10.1%) acquired a nosocomial infection in the postoperative period. Pneumonia was the most frequent (4.2%) nosocomial infection. Three independent risk factors for the development of a nosocomial infection were identified: cardiopulmonary bypass time, kidney failure and emergency surgery. The stay in the ICU was significantly higher in patients who developed a nosocomial infection (16.6 ±â€¯38.8 vs. 4.4 ±â€¯17.8, P < 0.001). The mortality rate of patients who acquired a nosocomial infection was significantly greater (18%) than that of patients who did not acquire a nosocomial infection (5%) (P < 0.001). The 90-day survival was greater in the group of patients without nosocomial infection (log rank 27.55, P < 0.001). The dynamic modelling of 90-day mortality revealed that in the first week, cardiopulmonary bypass time (HR = 1.00, 95% CI 1.00-1.02, P < 0.001) and emergency surgery (HR = 0.12, 95% CI 0.04-0.37, P < 0.001) were the most important risk factors for mortality, while after the first week, nosocomial infection (HR = 6.23, 95% CI 2.49-15.63, P < 0.001) was the main risk factor, followed by cardiopulmonary bypass time (HR = 1.01, 95% CI 1.00-1.01, P = 0.001) and EuroSCORE (HR = 1.03, 95% CI 1.00-1.06, P = 0.008). CONCLUSIONS: Nosocomial infections after cardiac surgery constitute the main independent risk factor for mortality after the first week of surgery. These data suggest that its prevention following cardiac surgery must be prioritised to improve patient outcomes.

IFNL3 rs12980275 Polymorphism Predicts Septic Shock-Related Death in Patients Undergoing Major Surgery: A Retrospective Study.

Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan-Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.

Gene Expression Patterns Distinguish Mortality Risk in Patients with Postsurgical Shock.

Nowadays, mortality rates in intensive care units are the highest of all hospital units. However, there is not a reliable prognostic system to predict the likelihood of death in patients with postsurgical shock. Thus, the aim of the present work is to obtain a gene expression signature to distinguish the low and high risk of death in postsurgical shock patients. In this sense, mRNA levels were evaluated by microarray on a discovery cohort to select the most differentially expressed genes between surviving and non-surviving groups 30 days after the operation. Selected genes were evaluated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort to validate the reliability of data. A receiver-operating characteristic analysis with the area under the curve was performed to quantify the sensitivity and specificity for gene expression levels, which were compared with predictions by established risk scales, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA). IL1R2, CD177, RETN, and OLFM4 genes were upregulated in the non-surviving group of the discovery cohort, and their predictive power was confirmed in the validation cohort. This work offers new biomarkers based on transcriptional patterns to classify the postsurgical shock patients according to low and high risk of death. The results present more accuracy than other mortality risk scores.

Nosocomial Vs. Community-Acquired Infective Endocarditis in Spain: Location, Trends, Clinical Presentation, Etiology, and Survival in the 21st Century.

Major changes have occurred in the epidemiology and etiology of infective endocarditis (IE). Nevertheless, the differences between nosocomial infective endocarditis (NIE) and community-acquired infective endocarditis (CIE) have not been addressed in a population-based study. We conducted a retrospective, nationwide, temporal trend study from 1997 to 2014 analyzing the epidemiology, clinical, geographical, meteorological characteristics of patients diagnosed with IE in Spain, to distinguish NIE from CIE. Among 25,952 patients with IE (62.2 ± 18·6 years; 65.9% men), 45.9% had NIE. The incidence of IE increased from 2.83 to 3.73 due to the NIE incidence increment with a decline in CIE. Patients with NIE were older (63.8 years vs. 60.8 years, p < 0·001), presented a higher Charlson index (1.22 vs. 1.03, p < 0.001), a greater history of implanted cardiac devices (8.7% vs. 4.6%, p < 0.001), and higher mortality (31.5% vs. 21.7%, p < 0.001). The most frequent microorganism for both NIE and CIE was Staphylococcus (p < 0.001), and the North reported a higher incidence (p < 0.001). Risk factors of mortality for NIE were age, Charlson index, hemodialysis, shock, heart failure, and stroke. Risk factors for CIE included female sex, renal disease, and cardiac-device carriers. The etiology of IE shifted from community origins to mostly nosocomial-associated infections. Higher morbidity, mortality, and poorer outcomes are associated with NIE.