Incidence of hospital-acquired infections due to carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa in critically ill patients in Italy: a multicentre prospective cohort study.

Background: Carbapenem-Resistant Gram-Negative Bacteria, including Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA), are common causes of infections in intensive care units (ICUs) in Italy.

Objective: This prospective observational study evaluated the epidemiology, management, microbiological characterization, and outcomes of hospital-acquired CRE or CRPA infections treated in selected ICUs in Italy.

Methods: The study included patients with hospital-acquired infections due to CRE and CRPA treated in 20 ICUs from June 2021 to February 2023.

Anticoagulation Among Patients Hospitalized for COVID-19 : A Systematic Review and Prospective Meta-analysis.

Background: Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent.

Purpose: To estimate the association of higher- versus lower-dose anticoagulation with clinical outcomes.

Data Sources: Randomized trials were identified from the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.

The renin-angiotensin-aldosterone-system in sepsis and its clinical modulation with exogenous angiotensin II.

Dysregulation of the renin-angiotensin-aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent. In this review, we report a multinational and multi-disciplinary expert panel discussion on the role and implications of RAAS modulation in sepsis and the use of exogenous angiotensin II.

Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials.

Background: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.

Methods: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation.

Management of Sepsis in the First 24 Hours: Bundles of Care and Individualized Approach.

Early diagnosis and prompt management are essential to enhance the outcomes of patients with sepsis and septic shock. Over the past two decades, evidence-based guidelines have guided appropriate treatment and recommended the implementation of a bundle strategy to deliver fundamental treatments within the initial hours of care. Shortly after its introduction, the implementation of a bundle strategy has led to a substantial decrease in mortality rates across various health care settings.

Perioperative Use of IgM-Enriched Immunoglobulins in Liver Transplantation Recipients at High Risk for Infections: A Preliminary Study.

: Infections frequently occur after orthotopic liver transplantation (OLT) and are associated with increased mortality. In 2018, we introduced perioperative administration of intravenous immunoglobulin enriched in IgM as an optional therapy in recipients at a high risk of infection. This preliminary study evaluated whether this preparation reduced infections in the early post-transplantation period.

Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes.

The Interplay between Antibiotics and the Host Immune Response in Sepsis: From Basic Mechanisms to Clinical Considerations: A Comprehensive Narrative Review.

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.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23.

Background: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies.

Intravenous fosfomycin in combination regimens as a treatment option for difficult-to-treat infections due to multi-drug-resistant Gram-negative organisms: A real-life experience.

Aim: To investigate the efficacy of intravenous (IV) fosfomycin as combination therapy for treatment of difficult-to-treat (DTT) acute and subacute infections with multi-drug-resistant (MDR) Gram-negative bacteria (GNB), and risk factors associated with 90-day mortality.

Methods: A retrospective, observational, monocentric study enrolled patients treated with IV fosfomycin in combination regimens (≥72 h) for proven DTT-MDR-GNB infection. Multi-variate regression analysis identified independent risk factors for 90-day mortality.

Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.

Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice.

High versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: a study protocol for the HISTAP randomized clinical trial.

Background: The intraoperative period is often characterized by hemodynamic instability, and intraoperative hypotension is a common complication. The optimal mean arterial pressure (MAP) target in hypertensive patients is still not clear. We hereby describe the protocol and detailed statistical analysis plan for the high versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: the HISTAP randomized clinical trial.

Association between Pulmonary Aspergillosis and Reactivation in Critically Ill COVID-19 Patients: A Prospective Observational Cohort Study.

COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from 25 February 2020 to 8 May 2022.

The Association of Procalcitonin and C-Reactive Protein with Bacterial Infections Acquired during Intensive Care Unit Stay in COVID-19 Critically Ill Patients.

In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identifying bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with secondary infections acquired during ICU stay in critically ill COVID-19 patients. This observational study included adult patients admitted to three COVID-19 intensive care units (ICUs) from February 2020 to May 2022 with respiratory failure caused by SARS-CoV-2 infection and ICU stay ≥ 11 days.

Empiric treatment of patients with sepsis and septic shock and place in therapy of cefiderocol: a systematic review and expert opinion statement.

Carbapenem-resistant Gram-negative bacteria are frequent causes of sepsis and septic shock in intensive care unit (ICU) and thus considered a public health threat. Until now, the best available therapies consist of combinations of preexisting or new antibiotics with β-lactamase inhibitors (either new or preexisting). Several mechanisms of resistance, especially those mediated by metallo-β-lactamases (MBL), are responsible for the inefficacy of these treatments, leaving an unmet medical need.