Following the success of Spotlight on the Relationship between Sepsis and Infection: from Mechanisms to Therapy
we are pleased to present Volume II of this collection.
The dysregulated host response to infection leading to sepsis and septic shock is a life-threatening event that, despite advances in organ support and antimicrobial therapy, is associated with a mortality rate of >30%. Despite implementation of international guidelines supporting early-goal directed therapy, recent randomized trials have demonstrated that these interventions do not improve survival of septic patients. This evidence warrants an urgent clarification of the molecular mechanisms underlying clinical responses in patients with sepsis or septic shock. Therefore, there is an urgent global need to improve the prevention, recognition, diagnosis and management of sepsis. The key to improving these processes lies in acquiring in-depth knowledge of the intricate interplay between host defence, infection and pathogen virulence as well as timing and type of interventions that are most effective according to the personal characteristics of individual patients. In recent years, infections due to multidrug-resistant (MDR) Gram-negative and Gram-positive pathogens, have been increasingly observed among critically ill patients admitted to the intensive care unit, but also in medicine wards. In this scenario, a predominant role of fungal aetiology was associated with development of severe infections.
The management of critically ill patients includes early diagnosis and immediate administration of antimicrobials. Previous observations about septic patients highlighted the crucial role of timely empirical antimicrobial treatment and the importance of a definitive anti-infective therapy with in vitro activity against the microbial isolates, emphasizing also the importance of an adequate and early source control of infection. Moreover, the pharmacokinetic and pharmacodynamic properties of antibiotics should be considered due to changes in clearance and volume of distribution that are frequently observed in critically ill patients, with the potential to influence concentration of the drug at site of infections.
Recently, new drugs for the treatment of severe infections have been approved but their role in clinical practice should be focused.
As aforementioned, the knowledge of mechanisms related to progression from sepsis to septic shock and adequate management of patients, including choice and dosages of antimicrobials, prove crucial to improve the outcome of septic patients.
In this Research Topic, we aim to address the following themes:
• The key roles of mechanisms of sepsis susceptibility, clinical presentation and outcomes;
• To identify new avenues for healthcare intervention and to accelerate improved treatments for sepsis;
• Explore sepsis with a specific focus on MDR aetiology and new antimicrobial therapies.