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Sepsis: New Insights into Diagnosis and Treatment
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Sepsis: New Insights into Diagnosis and Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: 30 July 2025 | Viewed by 5167

Special Issue Editors

Prof. Dr. Francesco Forfori

E-Mail Website
Guest Editor
Anesthesia and Intensive Care, Anesthesia and Resuscitation Department, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy
Interests: sepsis; continuous renal replacement therapy; blood purification; ultrasound; adjuvant therapy; ARDS; nutrition; infection disease
Special Issues, Collections and Topics in MDPI journals
Dr. Etrusca Brogi

E-Mail Website
Guest Editor
Department Anaesthesia and Intensive Care, University of Pisa, 56126 Pisa, Italy
Interests: sepsis; ECMO; ultrasound; haemodynamic management; adjuvant therapy; ARDS

Special Issue Information

Dear Colleagues,

Sepsis represents a life-threatening condition with a huge impact on health care costs. Further, Sepsis is a “time-dependent” disease; the outcome is highly influenced by the prompt detection and efficiency of the management, even from the very “first hour”. Due to the centrality of the complex interactions between the infectious insult and the host's immune response, a deeper understanding of the mechanisms involved in the dysregulation host response is mandatory.

Interestingly, It is now clear that the individual genomic profile is partly responsible for the interindividual variability of the clinical evolution of sepsis. In light of this evidence, immunomorinitoring and immunotherapy have gained increasing recognition in recent decades. Unfortunately, until now, evidence has not supported the extensive introduction of adjuvant therapy in current clinical practice.

In this Special Issue, we invite researchers and clinicians to submit their work, including original clinical research studies, meta-analyses, and systematic reviews, that will provide additional insight on the diagnosis and treatment of septic shock.

Prof. Dr. Francesco Forfori
Dr. Etrusca Brogi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sepsis and sepsis subphenotypes
  • adjuvant therapy
  • blood purification strategies
  • immunomonitoring and immunotherapy
  • the microbiome in sepsis
  • crosstalk in multi-organ failure (MOF)
  • ultrasound in sepsis (POCUS)
  • sepsis-induced coagulophaty and DIC
  • antibiotic therapy
  • multimodal approaches to surgical source control

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Published Papers (5 papers)

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Research

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15 pages, 593 KiB  
Article
Evaluating Sepsis Management and Patient Outcomes: A Comprehensive Retrospective Study of Clinical and Treatment Data
by Sahbanathul Missiriya Jalal, Suhail Hassan Jalal, Abeer Abbas Alabdullatif, Kamilah Essa Alasmakh, Zahraa Hussain Alnasser and Wadiah Yousef Alhamdan
J. Clin. Med. 2025, 14(10), 3555; https://doi.org/10.3390/jcm14103555 - 19 May 2025
Viewed by 188
Abstract
Background/Objectives: Sepsis, as a major cause of mortality worldwide, requires timely diagnosis and prompt treatment to improve patient outcomes. In this study, we evaluated sepsis management strategies and their impact on clinical outcomes in hospitalized patients. Methods: A retrospective study was conducted by [...] Read more.
Background/Objectives: Sepsis, as a major cause of mortality worldwide, requires timely diagnosis and prompt treatment to improve patient outcomes. In this study, we evaluated sepsis management strategies and their impact on clinical outcomes in hospitalized patients. Methods: A retrospective study was conducted by analyzing clinical and treatment data from the electronic records of sepsis patients who had been admitted to tertiary care hospitals in eastern Saudi Arabia. Using systematic sampling, the details of eligible patients were obtained. Data were collected on patient demographics, vital signs, Sequential Organ Failure Assessment (SOFA) and laboratory parameters, treatment (antibiotic therapy, vasopressor use, or fluid resuscitation), and outcomes (survival in hospital). Statistical analyses were performed to assess the association between clinical and treatment strategies and patient outcomes. Results: A total of 234 sepsis cases were analyzed, of which 70.9% were survivors and 29.1% were non-survivors. Patients aged 60 years and above were the most affected. Statistically significant differences were observed across all of the measured vital sign variables and outcomes (p < 0.0001). Based on SOFA scores, 56.41% of patients were assessed as having a moderate risk. Through our comparison of clinical and laboratory parameters between survivors and non-survivors, significant differences were found in all of the measured variables (p < 0.0001). The odds of survival were significantly higher in those who received early administration of broad-spectrum antibiotics (OR = 4.9449, p = 0.0001), vasopressor therapy (OR = 1.9408, p = 0.0262), and fluid resuscitation OR = 11.035, p = 0.0001). Conclusions: The results of this study highlight the importance of early sepsis recognition, prompt antibiotic therapy, and standardized protocol adherence in improving patient outcomes and reducing mortality and morbidity. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
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12 pages, 546 KiB  
Article
Low, Intermediate, and High Glutamine Levels Are Progressively Associated with Increased Lymphopenia, a Diminished Inflammatory Response, and Higher Mortality in Internal Medicine Patients with Sepsis
by Filippo Mearelli, Alessio Nunnari, Federica Chitti, Annalisa Rombini, Alessandra Macor, Donatella Denora, Luca Messana, Marianna Scardino, Ilaria Martini, Giulia Bolzan, Noemi Merlo, Fabio Di Paola, Francesca Spagnol, Chiara Casarsa, Nicola Fiotti, Venera Costantino, Verena Zerbato, Stefano Di Bella, Carlo Tascini, Daniele Orso, Filippo Giorgio Di Girolamo and Gianni Bioloadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(10), 3313; https://doi.org/10.3390/jcm14103313 - 9 May 2025
Viewed by 331
Abstract
Background: The pathophysiological mechanisms underlying altered plasma glutamine concentrations in sepsis remain poorly understood. Identifying clinical, immunological, and metabolic correlates of glutamine fluctuations is crucial to advancing precision medicine, developing targeted therapies, and improving survival outcomes in septic patients. Methods: We enrolled 469 [...] Read more.
Background: The pathophysiological mechanisms underlying altered plasma glutamine concentrations in sepsis remain poorly understood. Identifying clinical, immunological, and metabolic correlates of glutamine fluctuations is crucial to advancing precision medicine, developing targeted therapies, and improving survival outcomes in septic patients. Methods: We enrolled 469 patients with sepsis and assessed inflammatory markers—including body temperature, white blood cell count, and C-reactive protein levels—upon admission to the internal medicine unit. Lymphocyte count and plasma concentrations of glutamine, glutamic acid, 5-oxoproline, phenylalanine, tyrosine, and leucine were measured using gas chromatography–mass spectrometry. Patients were stratified into three groups based on plasma glutamine levels. Mortality was recorded at 30 days and 6 months. Results: Low, intermediate, and high glutamine levels were observed in 46% (n = 217), 47% (n = 218), and 7% (n = 34) of patients, respectively. Patients with hyperglutaminemia exhibited significantly lower body temperature, white blood cell and lymphocyte counts, C-reactive protein levels, and glutamic acid-to-5-oxoproline ratio (a surrogate marker of glutathione availability), along with elevated phenylalanine levels, leucine levels, and tyrosine-to-phenylalanine ratio (all p < 0.01). Metabolic disruption and mortality increased progressively across glutamine level groups. Kaplan–Meier analysis demonstrated significantly higher mortality in patients with elevated glutamine levels at both 30 days (log-rank p = 0.03) and 6 months (log-rank p = 0.05). Conclusions: At baseline, increasing plasma glutamine levels are associated with progressively deeper lymphopenia, more pronounced metabolic derangement, and higher short- and long-term mortality in patients with sepsis. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
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Review

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25 pages, 3799 KiB  
Review
Immunomodulation in Pediatric Sepsis: A Narrative Review
by Gabriella Bottari, Fabio Silvio Taccone, Angelica Corrias, Mariangela Irrera, Paolo Currao, Michele Salvagno, Corrado Cecchetti and Didier Payen
J. Clin. Med. 2025, 14(9), 2983; https://doi.org/10.3390/jcm14092983 - 25 Apr 2025
Viewed by 398
Abstract
Pediatric sepsis presents a unique clinical challenge due to the distinct characteristics of the developing immune system. The immune response in children differs significantly from that in adults, exhibiting a unique combination of resistance, disease tolerance, and resilience. These factors influence the clinical [...] Read more.
Pediatric sepsis presents a unique clinical challenge due to the distinct characteristics of the developing immune system. The immune response in children differs significantly from that in adults, exhibiting a unique combination of resistance, disease tolerance, and resilience. These factors influence the clinical presentation and prognosis of pediatric patients with sepsis. Over the past few years, various studies have explored the role of immunomodulatory therapies in managing sepsis, including the use of immunoglobulins, corticosteroids, monoclonal antibodies, and immunostimulatory treatments. However, the heterogeneity of the clinical presentations and individual responses makes it difficult to identify universally effective treatments. Recent research has highlighted the importance of a personalized approach based on specific biomarkers and patient phenotyping. Extracorporeal blood purification techniques have emerged as promising strategies for the modulation of hyperinflammation. However, strong evidence supporting their routine use in pediatric sepsis is lacking. This review provides a comprehensive overview of the current knowledge of the immune response in pediatric sepsis and discusses the main immunomodulatory strategies and future perspectives for personalized therapy. A deeper understanding of the immunological differences between children and adults could improve the prognosis and treatment efficacy, paving the way for new approaches to pediatric sepsis management. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
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15 pages, 248 KiB  
Review
Antibiotic Stability and Feasibility in Elastomeric Infusion Devices for OPAT: A Review of Current Evidence
by Chiara Moreal, Luca Martini, Francesca Prataviera, Carlo Tascini and Simone Giuliano
J. Clin. Med. 2025, 14(8), 2722; https://doi.org/10.3390/jcm14082722 - 15 Apr 2025
Viewed by 472
Abstract
Background/Objectives: Elastomeric infusion pumps have emerged as a transformative tool in outpatient parenteral antimicrobial therapy (OPAT), enabling continuous intravenous administration outside hospital settings, enhancing patient autonomy, reducing healthcare costs, and playing a role in antimicrobial stewardship. This aim of this review is [...] Read more.
Background/Objectives: Elastomeric infusion pumps have emerged as a transformative tool in outpatient parenteral antimicrobial therapy (OPAT), enabling continuous intravenous administration outside hospital settings, enhancing patient autonomy, reducing healthcare costs, and playing a role in antimicrobial stewardship. This aim of this review is to update current evidence on antibiotic stability in elastomeric infusion pumps, analyzing environmental factors, clinical efficacy, and practical challenges associated with OPAT implementation. Methods: A narrative review was conducted using PubMed and the Cochrane Library, focusing on studies published between 2022 and 2025. Included studies assessed antibiotic stability in elastomeric pumps under real-world and laboratory conditions, examining factors such as temperature sensitivity, light exposure, and material interactions. Results: Findings indicate considerable variability in antibiotic stability, with some agents maintaining prolonged efficacy while others degrade rapidly under certain conditions. Antibiotics with greater stability are better suited for OPAT, whereas those prone to degradation present challenges for continuous infusion. Clinical studies report favorable treatment outcomes, including high cure rates and manageable adverse event profiles. However, discrepancies between laboratory-controlled conditions and real-world settings highlight the necessity for more comprehensive stability evaluations to ensure optimal antibiotic selection and administration in OPAT programs. Conclusions: Optimizing antibiotic formulations, standardizing stability protocols, and advancing elastomeric pump technologies are essential for enhancing OPAT effectiveness. Future research should focus on real-world simulation studies and refining device materials to expand the range of stable antibiotics, ensuring safer and more efficient outpatient antimicrobial therapy. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
20 pages, 578 KiB  
Review
Artificial Intelligence in Sepsis Management: An Overview for Clinicians
by Elena Giovanna Bignami, Michele Berdini, Matteo Panizzi, Tania Domenichetti, Francesca Bezzi, Simone Allai, Tania Damiano and Valentina Bellini
J. Clin. Med. 2025, 14(1), 286; https://doi.org/10.3390/jcm14010286 - 6 Jan 2025
Viewed by 3142
Abstract
Sepsis is one of the leading causes of mortality in hospital settings, and early diagnosis is a crucial challenge to improve clinical outcomes. Artificial intelligence (AI) is emerging as a valuable resource to address this challenge, with numerous investigations exploring its application to [...] Read more.
Sepsis is one of the leading causes of mortality in hospital settings, and early diagnosis is a crucial challenge to improve clinical outcomes. Artificial intelligence (AI) is emerging as a valuable resource to address this challenge, with numerous investigations exploring its application to predict and diagnose sepsis early, as well as personalizing its treatment. Machine learning (ML) models are able to use clinical data collected from hospital Electronic Health Records or continuous monitoring to predict patients at risk of sepsis hours before the onset of symptoms. Background/Objectives: Over the past few decades, ML and other AI tools have been explored extensively in sepsis, with models developed for the early detection, diagnosis, prognosis, and even real-time management of treatment strategies. Methods: This review was conducted according to the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research Type) framework to define the study methodology. A critical overview of each paper was conducted by three different reviewers, selecting those that provided original and comprehensive data relevant to the specific topic of the review and contributed significantly to the conceptual or practical framework discussed, without dwelling on technical aspects of the models used. Results: A total of 194 articles were found; 28 were selected. Articles were categorized and analyzed based on their focus—early prediction, diagnosis, mortality or improvement in the treatment of sepsis. The scientific literature presents mixed outcomes; while some studies demonstrate improvements in mortality rates and clinical management, others highlight challenges, such as a high incidence of false positives and the lack of external validation. This review is designed for clinicians and healthcare professionals, and aims to provide an overview of the application of AI in sepsis management, reviewing the main studies and methodologies used to assess its effectiveness, limitations, and future potential. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
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