Search Results (60)

Background: Community-acquired pneumonia (CAP) is the leading cause of mortality in children from middle- to low-income countries; diagnosing CAP includes clinical evaluation, laboratory testing and pulmonary imaging. Lung ultrasound (LUS) is a sensitive, accessible, non-invasive, non-radiant method for accurately evaluating the lung involvement in acute diseases. Whether LUS findings can be correlated with CAP’s severity or sepsis risk remains debatable. This study aimed to increase the importance of LUS in diagnosing and monitoring CAP. We analyzed 102 children aged 1 month up to 18 years, hospital admitted with CAP. Mean age was 5.71 ± 4.85 years. Underweight was encountered in 44.11% of children, especially below 5 years, while overweight was encountered in 11.36% of older children and adolescents. Patients with CAP presented with fever (79.41%), cough (97.05%), tachypnea (18.62%), respiratory failure symptoms (20.58%), chest pain (12.74%) or poor feeding. Despite the fact that 21.56% had clinically occult CAP and six patients (5.88%) experienced radiologically occult pneumonia, CAP diagnosis was established based on anomalies detected using LUS. Conclusions: Detailed clinical examination with abnormal/modified breath sounds and/or tachypnea is suggestive of acute pneumonia. LUS is a sensitive diagnostic tool. A future perspective of including LUS in the diagnosis algorithm of CAP should be taken into consideration. Full article

Background: Intravascular albumin mass represents the total quantity of albumin circulating within the bloodstream and may serve as a physiologically relevant marker of vascular integrity and fluid distribution in sepsis. While low serum albumin levels are acknowledged as prognostic indicators, dynamic assessments based on albumin mass remain insufficiently explored in patients outside the intensive care unit. Objectives: To describe the temporal changes in intravascular albumin mass in patients with community-acquired sepsis and to examine its relationship with fluid balance and thirty-day mortality. Methods: This prospective observational study encompassed 247 adults diagnosed with community-acquired sepsis who were admitted to a high-dependency hospital ward specializing in acute medical care. The intravascular albumin mass was calculated daily for a duration of up to five days, utilizing plasma albumin concentration and estimated plasma volume derived from anthropometric and hematologic data. Net albumin leakage was defined as the variation in intravascular albumin mass between consecutive days. Fluid administration and urine output were documented to ascertain cumulative fluid balance. Repeated-measures statistical models were employed to evaluate the associations between intravascular albumin mass, fluid balance, and mortality, with adjustments made for age, comorbidity, and clinical severity scores. Results: The intravascular albumin mass exhibited a significant decrease during the initial five days of hospitalization and demonstrated an inverse correlation with the cumulative fluid balance. A greater net leakage of albumin was associated with a positive fluid balance and elevated mortality rates. Furthermore, a reduced intravascular albumin mass independently predicted an increased risk of mortality at thirty days. Conclusions: A reduction in intravascular albumin mass may suggest ineffective fluid retention and the onset of capillary leak syndrome. This parameter holds promise as a clinically valuable, non-invasive indicator for guiding fluid resuscitation in cases of sepsis. Full article

Background: Sepsis remains a leading cause of mortality worldwide, and understanding endothelial damage is crucial for improving patient outcomes. Endothelial dysfunction in sepsis contributes to coagulopathy, increased capillary permeability, and vasoplegia, but the interplay between these processes remains underexplored. The study aims to evaluate the clinical relationship between those factors due to sepsis-induced endothelial damage. Methods: A prospective single-center study on 75 community-acquired septic patients admitted to an Intermediate Care Unit. The Sepsis-Induced Coagulopathy (SIC) score, serum albumin (as a surrogate for capillary leak), and Total Peripheral Resistance Index (TPRI) (as a surrogate for vasoplegia) were assessed. Structural Equation Modeling (SEM) explored the relationship between variables, hypothesizing a common latent factor (endothelial damage). Principal Component Analysis assessed the shared variance among variables. Results: The mean SIC score was 3.4 (SD 1.3), with 44% of patients affected. TPRI and albumin had mean values of 1954 (SD 738) and 2.58 (SD 0.59), respectively, both negatively correlated with SIC: TPRI −0.263 (p = 0.023) and albumin −0.454 (p < 0.001). SEM showed SIC, albumin, and TPRI are associated with a latent factor (endothelial damage), explaining 68% of the variance (CFI = 1.000, RMSEA = 0.000). Albumin was inversely correlated (p = 0.004), and TPRI was significantly associated (p = 0.003). Conclusions: This pilot study suggests that coagulopathy, increased vascular permeability, and vasoplegia may be clinically interrelated manifestations of endothelial injury in sepsis. These findings support the feasibility of modeling a unified pathophysiological construct using accessible bedside data, potentially guiding future individualized approaches in sepsis management. Full article

Background: Sepsis-induced coagulopathy (SIC) and hypoalbuminemia represent distinct yet interrelated manifestations of endothelial dysfunction in sepsis. While both have been individually associated with increased mortality, their combined prognostic value remains unexplored. This study aimed to assess the relationship between the SIC score and serum albumin levels and to evaluate their integrated role in predicting mortality and bleeding risks in septic patients. Methods: We conducted a prospective observational study enrolling adult patients with community-acquired sepsis admitted to an Intermediate Medical Care Unit between January 2023 and June 2024. The primary outcome was 30-day all-cause mortality. The secondary outcome was the occurrence of ISTH-defined major bleeding. Multivariable logistic regression and Net Reclassification Improvement (NRI) analyses were performed to evaluate the predictive value of albumin when added to the SIC score. Results: A total of 413 patients were enrolled; 18.4% had a positive SIC score. The serum albumin and SIC score were inversely correlated (r = −0.189, p < 0.001). Both variables were independently associated with 30-day mortality and major bleeding. The addition of albumin significantly improved the predictive performance of the SIC score (NRI = 0.276 for mortality; NRI = 0.268 for bleeding; both p = 0.003). The cluster analysis identified distinct phenotypes based on albumin and SIC profiles, with differing clinical trajectories and transfusion needs. Conclusions: The combined assessment of the SIC score and serum albumin enhances early risk stratification in sepsis. This dual-parameter approach may support more accurate prognostication and individualized management in septic patients. Full article

Background and Objectives: Sepsis is one of the major causes of death in modern society. This study is part of the FUSE (Functional Genomics in Severe Sepsis) project under the Human Functional Genomics Romania initiative. Our aim was to assess the epidemiology of sepsis in a tertiary academic hospital in southwestern Romania. Materials and methods: The study enrolled 184 patients with severe infections between May 2017 and November 2019, following the Sepsis-2 guidelines (SIRS criteria). Results: The present cohort of community-acquired severe infections shows respiratory and urinary tract as main sites of severe infection. The demographic and clinical characteristics of this Romanian study group are in line with those of other severe infection European cohorts. However, the predominance of confirmed Clostridium difficile cases represents a strong deviation, raising significant concerns for the communities to which the patients belong. Conclusions: Sepsis, with its complex pathophysiology and clinical presentation, remains one of the most daunting global health issues. In our cohort, the high number of Clostridium difficile cases prompts high vigilance and immediate intervention. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been linked with sepsis outcomes. However, the immune mechanisms by which MASLD aggravates sepsis severity are unknown. This prospective cohort study aimed to analyze serum cytokine and chemokine kinetics in patients with MASLD and community-acquired sepsis. Out of the 124 patients, 68 (55%) were diagnosed with MASLD. There were no differences in age, sex, comorbidities, baseline sepsis severity, or etiology between the groups. Serum concentrations of 27 cytokines and chemokines on admission and day 5 of hospitalization were analyzed using a multiplex bead-based assay. Patients with MASLD had significantly higher serum concentrations of IL17A, IL-23, IL-33, CXCL10 and TGF-β1. Different cytokine kinetics were observed; patients with MASLD had a decrease in IL-10, IL-23, CXCL10 and TGF-β1, and an increase in IL-33, CXCL5 and CXCL1 on day 5. In the non-MASLD group, there was a decrease in IFN-γ, IL-6, IL-23 and CCL20, and an increase in CCL11 and CXCL5. While TGF-β1 significantly increased in non-MASLD, in MASLD, it decreased on day 5. Kinetics of TGF- β1 and CCL11 were associated with mortality in patients with MASLD. In conclusion, MASLD is linked with distinct cytokine and chemokine profiles during sepsis. Full article

Preterm and low-birth-weight neonates are particularly susceptible to methicillin-resistant Staphylococcus aureus (MRSA) colonization, whereas MRSA infection is associated with significant neonatal morbidity and mortality globally. The objective of our study was to examine the current body of knowledge about molecular traits, epidemiology, risk factors, clinical presentation, decolonization techniques, and available treatments for MRSA infection in neonates. MRSA strains that predominate in neonatal units, namely healthcare-associated (HA)-MRSA, differ from community-acquired (CA)-MRSA strains in molecular characteristics, toxin synthesis, including Panton-Valentine leukocidin, and resistance to antibiotics. Colonization with MRSA predisposes neonates to infection. The clinical impact of MRSA infection includes bacteremia, sepsis, pneumonia, endocarditis, osteomyelitis, septic arthritis, skin and soft tissue infections, and toxic shock syndrome. To reduce MRSA transmission, colonization, and infection, customized approaches are required, including continuous surveillance of MRSA epidemiology, new techniques for detecting MRSA resistance, and the application of basic preventive measures. Antimicrobial susceptibility monitoring is essential to identify the best empirical antimicrobial treatments. The growing antibiotic resistance of MRSA remains challenging, and vancomycin is still the best option. Further extensive research and surveillance are warranted to explore the genetic diversity and prevalence of MRSA. Full article

In sepsis, a balanced pro-inflammatory and anti-inflammatory response results in the bacterial clearance and resolution of inflammation, promoting clinical recovery and survival. Semaphorins, a large family of secreted and membrane-bound glycoproteins, are newly recognized biomarkers and therapeutic targets in immunological and neoplastic disorders. Although semaphorins might also be a crucial part of host defense responses to infection, their role in sepsis is yet to be determined. This study aimed to analyze the association of serum semaphorin concentrations with sepsis severity and outcomes. Serum semaphorin concentrations (SEMA3A, SEMA3C, SEMA3F, SEMA4D, and SEMA7A) were measured in 115 adult patients with community-acquired sepsis and 50 healthy controls. While SEMA3A was decreased, SEMA3C, SEMA3F, SEMA4D, and SEMA7A were increased in sepsis patients. All analyzed SEMA showed good accuracy in identifying patients with sepsis. SEMA kinetics were related to sepsis complications; SEMA3A, SEMA3C, SEMA3F, and SEMA4D with respiratory failure; SEMA3C and SEMA7A with acute kidney injury; and SEMA3C and SEMA3F were related to septic shock. Importantly, SEMA3A, SEMA3C, SEMA4D, and SEMA7A were associated with 28-day mortality. In conclusion, we provide evidence that semaphorins are associated with sepsis course and outcomes. Full article

Many patients with community-acquired diabetic foot infections (DFI) receive systemic (empirical) antibiotic treatments before surgical interventions, often by the general practitioner. Sometimes, hospital clinicians prescribe them before surgery to reduce the infection inoculum and preserve soft tissue for immediate wound closure in case of residual infection after surgery. In contrast, the international guidelines (IWGDF) advocate against presurgical antibiotic use in routine situations without severe progredient soft tissue infections and/or sepsis. We run several retrospective and prospective cohorts of DFI and retrospectively analyze the influence of presurgical antibiotic therapy (as binary (yes/no) or continuous (in days) variables) on failures after a combined surgical and medical treatment. In our large database, the presence, choice, administration routes, or duration of preoperative antibiotic therapy did not improve the postoperative outcomes of operated diabetic foot infections or prevent their failures. In turn, this lack of influence leaves space for enhanced antibiotic stewardship in the management of DFI. Full article

Klebsiella pneumoniae is well recognized as a serious cause of infection in healthcare-associated settings and immunocompromised individuals; however, accumulating evidence from resource-limited nations documents an alarming rise in community-acquired K. pneumoniae infections, manifesting as bacteremia and pneumonia as well as neonatal sepsis. The emergence of hypervirulent and antibiotic-resistant K. pneumoniae strains threatens treatment options for clinicians. Effective vaccination strategies could represent a viable alternative that would both preempt the need for antibiotics to treat K. pneumoniae infections and reduce the burden of K. pneumoniae disease globally. There are currently no approved K. pneumoniae vaccines. We review the evidence for K. pneumoniae lipopolysaccharide (LPS) as a vaccine and immunotherapeutic target and discuss the role of antibodies specific for the core or O-antigen determinants within LPS in protection against Klebsiella spp. disease. We expand on the known role of the Klebsiella spp. capsule and O-antigen modifications in antibody surface accessibility to LPS as well as the in vitro and in vivo effector functions reported for LPS-specific antibodies. We summarize key hypotheses stemming from these studies, review the role of humoral immunity against K. pneumoniae O-antigen for protection, and identify areas requiring further research. Full article

Background and Objectives: The predictive value of changes in C-reactive protein (CRP), procalcitonin, and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. The aim of this study was to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of 230 patients admitted to the intensive care unit (ICU) with the diagnosis of sepsis and pneumonia-related septic shock between 1 April 2022 and 31 December 2023, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Materials and Methods: This single-center, retrospective, cross-sectional observational study included patients who developed sepsis and septic shock due to community-acquired pneumonia and were admitted to the ICU. Demographic data, 1-month and 90-day mortality rates, length of stay in the ICU, discharge to the ward or an outside facility, need for dialysis after sepsis, need for invasive or noninvasive mechanical ventilation during the ICU stay and the duration of this support, whether patients admitted with sepsis or septic shock required inotropic agent support during their stay in the ICU and whether they received monotherapy or combination therapy with antibiotics during their admission to the ICU, the Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score were analyzed. Additionally, CRP, procalcitonin, and leukocyte levels were recorded, and univariate and multivariate logistic regression analyses were performed to evaluate their effects on 1- and 3-month mortality outcomes. In all statistical analyses, a p-value of <0.05 was accepted as a significant level. Results: According to multivariate logistic regression analysis, low BMI, male gender, and high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p < 0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both the 1-month and 3-month mortality cases (p < 0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared with those who survived (p = 0.004). Conclusions: In patients with pneumoseptic or pneumonia-related septic shock, the persistent elevation and concurrent increase in PCT, CRP, and leukocyte values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality. Full article

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06–1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome. Full article

The aim of this study was to collect data and analyze mortality among patients hospitalized with community-acquired infections in the Faroe Islands. A prospective observational study was conducted in the Medical Department of the National Hospital of the Faroe Islands from October 2013 to April 2015. Cumulative all-cause, in-hospital, short-term, intermediate-term and long-term mortality rates were calculated. Kaplan–Meier survival curves comparing infection-free patients with infected patients of all severities and different age groups are presented. A log-rank test was used to compare groups. Mortality hazard ratios were calculated for subgroups using Cox regression multivariable models. There were 1309 patients without infection and 755 patients with infection. There were 51% female and 49% male patients. Mean age was 62.73 ± 19.71. Cumulative all-cause mortality and in-hospital mortality were highest in more severe forms of infection. This pattern remained the same for short-term mortality in the model adjusted for sex and age, while there were no significant differences among the various infection groups in regard to intermediate- or long-term survival after adjustment. Overall and short-term mortality rates were highest among those with severe manifestations of infection and those with infection compared to infection-free patients. Full article

Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and the immune system, aiming to clarify the involved mechanisms and their clinical impacts. From pre-clinical studies, antibiotics exhibit various immunomodulatory effects, including the regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation of the P38/Pmk-1 Pathway, inhibition of Matrix Metalloproteinases, blockade of nitric oxide synthase, and regulation of caspase-induced apoptosis. Additionally, antibiotic-induced alterations to the microbiome are associated with changes in systemic immunity, affecting cellular and humoral responses. The adjunctive use of antibiotics in sepsis patients, particularly macrolides, has attracted attention due to their immune-regulatory effects. However, there are limited data comparing different types of macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially in severe cases with a hyper-inflammatory response. While studies on septic shock have shown mixed results regarding mortality rates and immune response modulation, conflicting findings are also observed with macrolides in acute respiratory distress syndrome. In conclusion, there is a pressing need to tailor antibiotic therapy based on the patient’s immune profile to optimize outcomes in sepsis management. Full article

Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d’Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles—hyperinflammatory, low perfusion, and hypogammaglobulinemic—which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition. Full article