Immune dysregulation presents a significant clinical challenge due to its rapid progression and complex interplay between hyperinflammatory and immunosuppressive responses. Different responses from the innate and adaptive immune systems can result in diseases such as immunoparalysis, cytokine storms, and secondary infections. Current diagnostic methods remain non-specific and time-consuming, delaying targeted interventions. A compartmentalized approach to immune monitoring, distinguishing innate and acquired immune response functional differentiation, is essential for distinguishing between hyperactivation and suppression. Key biomarkers, including cytokines, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and CD4/CD8 counts, as well as Programmed Death Ligand-1 (PDL-1) and V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) regulators, can guide personalized treatment strategies. Although they need more clinical validation, novel therapeutic methods such as cytokine inhibitors, immunological stimulants, and immunomodulators have demonstrated promise. Early diagnosis and precision medicine developments could lead to better patient outcomes. Advances in non-coding RNAs have led to specific diagnostic panels based on microRNA (MiRNA) levels. A deeper understanding of immune imbalance in sepsis is critical for optimizing treatment and reducing mortality rates. This review highlights emerging diagnostic and therapeutic strategies to address the multifaceted nature of sepsis-related immune dysregulation.

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings.

Background: Bacterial co-infections in patients with viral pneumonia might increase mortality. In this study we aimed to evaluate their effect on the mortality of critically ill patients with viral pneumonia. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus and Cochrane from inception until 30 March 2025. We included studies comparing the effect on mortality of bacterial co-infections in critically ill patients with viral pneumonia. The risk of bias was assessed by the Newcastle–Ottawa Scale. Results: From 3643 studies, 10 were included in our study with a total of 2862 COVID-19 patients and 4573 influenza patients. Seven studies were retrospective and three prospective. In total, 359/2862 of the COVID-19 and 904/4573 of the influenza patients were co-infected. Co-infections increased mortality in five out of the six studies evaluating COVID-19 patients and in two out of the eight studies evaluating influenza patients. Conclusions: The majority of the included studies were retrospective, which may limit the accuracy of these results. The exclusion of non-English literature may have led to the omission of relevant data. Based on our results, the impact of bacterial co-infection may be more pronounced in patients with COVID-19 pneumonia admitted to the ICU than in patients with influenza pneumonia.

Background/Objectives: Antimicrobial resistance (AMR) has increased significantly over the years, contributing to a real challenge in the intensive care unit (ICU). The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer ceftazidime–avibactam (CAZ-AVI), meropenem–vaborbactam, and imipenem–relebactam. Treatment of such infections is challenging. In vitro and clinical data suggest that combinations of CAZ-AVI with aztreonam (ATM) and the use of two different carbapenems (double carbapenem therapy, DCT) may be an option for MBL-producing pathogens. The aim of our study was to evaluate the effectiveness of the combination CAZ-AVI + ATM and the effectiveness of DCT against MBL-producing K. pneumoniae infections in the critically ill, mechanically ventilated patients. Methods: This is a retrospective study conducted in the two ICUs of hospitals in central Greece. Mechanically ventilated patients admitted to the ICU were included in the study if they developed an infection by MBL-producing K. pneumoniae. Patients were divided into three groups: the first one consisted of patients who were treated with CAZ-AVI plus ATM (CAZ-AVI + ATM group), and the second group consisted of patients who received DCT (DCT group). The third group included patients who received appropriate antibiotic therapy other than CAZ-AVI + ATM and DCT (control group). The primary outcome of the study was the evolution of the sequential organ failure assessment (SOFA) score, and secondary outcomes were duration of mechanical ventilation (MV), ICU length of stay (LOS), and, finally, ICU mortality. Results: 108 patients were included in the study. 35 (32%) in the CAZ-AVI + ATM group, 31 (29%) in the DCT group, and the remaining 42 (39%) patients in the control group. The SOFA score was not statistically different on day 1, day 4, and day 7 of the infection among the three groups (p > 0.05). Duration of MV and ICU LOS were also similar. Finally, mortality did not differ between the groups [20 patients (57.1%) vs. 18 (58.1%) vs. 25 (59.5%) for CAZ-AVI + ATM, DCT and control group, respectively, p = 0.98]. Comparison between survivors and non-survivors revealed that independent risk factors for mortality were SOFA score at day 1 of infection and medical cause of admission (p < 0.05). Conclusions: Treatment with CAZ-AVI + ATM or DCT presented similar efficacy with appropriate antibiotic therapy for infections caused by MBL-producing K. pneumoniae strains. Larger studies are required to confirm the findings.

Introduction: Non-invasive ventilation (NIV) use in chronic obstructive pulmonary disease (COPD) exacerbation has increased significantly, however, approximately 1/3 of patients have either contraindications or cannot tolerate NIV therapy. Recently, nasal high flow (NHF) oxygen therapy has been introduced for the management of hypoxemic respiratory failure with positive physiological effects on respiratory support. These effects have also been observed in stable COPD patients with or without chronic hypercapnia. However, the use of NHF during acute COPD exacerbations (AECOPD) is still questionable with limited studies showing favourable outcomes. Objective: To evaluate NHF compared to NIV in patients with AECOPD and acute or acute on chronic hypercapnic respiratory failure. Method: A randomized controlled trial (RCT) in patients presenting with AECOPD (defined by pH >7.25 45mmHg) and are clinically indicated for NIV therapy (pH45mmHg, RR>23). Primary end point is treatment failure, secondary end points include, changes in respiratory variables, patient comfort and presence of pulmonary and extra-pulmonary complications. Results: So far, 27/498 participants have been enrolled. Mean age 74 (+/- 16) years. Seventy-eight percent were male. Prior to randomisation 9/27 (33.3%) had a pH between 7.30-7.35 and 18/27 (66.6%) had a pH between 7.25-7.29. Twelve patients (44%) were randomised to NIV and 15 (56%) to NHF. To date, treatment failure in the NIV cohort is 16% and 27% in the NHF cohort. Conclusions: These are preliminary data of a large RCT. Further and more detailed analysis will be presented at the Congress.