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Medicina
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New Strategies for Treatment of Sepsis
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New Strategies for Treatment of Sepsis

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 42268

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Antonio Mirijello

E-Mail Website
Guest Editor
IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
Interests: sepsis; internal medicine; addiction medicine; alcohol use disorders; alcoholic cardiomyopathy
Special Issues, Collections and Topics in MDPI journals
Dr. Alberto Tosoni

E-Mail Website
Guest Editor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Interests: sepsis; internal medicine; addiction medicine; gastroenterology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sepsis represents an emerging and one of the deadliest diseases worldwide, accounting for millions of preventable deaths every year, being the cause, directly or indirectly, of about half of all hospital deaths.

Until a decade ago, sepsis was managed almost exclusively by intensivists. Consequently most of the literature on this topic derives from studies conducted in Intensive Care Units (ICUs). However, in recent years, there has been a progressive increase in admissions of septic patients to non-ICU wards. The characteristics of septic population have gradually changed—being constantly older, more co-morbid and chronic—as well as the early management of sepsis and septic shock. As a consequence, there is the need for literature data derived both from intensive and non-intensive departments, in order to fill the gap of knowledge and for confirmatory purposes.

Being a time-dependent disease, sepsis requires a prompt recognition and a standardized approach for optimal treatment. In general medicine wards, the main limitations to this purpose are represented by the unfavorable proportion between patients and staff and by the lack of constant monitoring of vital functions.

We are still far from a full knowledge of the mechanisms underlying the development and progression of sepsis. It is in this context that, in the last few years, new scenarios have been opening for sepsis management, including the use of new diagnostic tools with less invasive approaches, the growing role of artificial intelligence, the development of better antibiotic therapy strategies and the optimization of involved health resourses.

This Special Issue has been brought about to disseminate the knowledge of a new blueprint for the treatment of sepsis, particularly among non-intensivists physicians.

Dr. Antonio Mirijello
Dr. Alberto Tosoni
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 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
  • septic shock
  • intensive care unit
  • internal medicine
  • non-intensive cares
  • prognostication
  • antibiotic treatment
  • artificial intelligence
  • immune response
  • non-invasive monitoring

Published Papers (14 papers)

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Editorial

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4 pages, 253 KiB  
Editorial
Sepsis: New Challenges and Future Perspectives for an Evolving Disease—Precision Medicine Is the Way!
by Antonio Mirijello and Alberto Tosoni
Medicina 2021, 57(10), 1109; https://doi.org/10.3390/medicina57101109 - 15 Oct 2021
Cited by 3 | Viewed by 1326
Abstract
Sepsis still remains the leading cause of in-hospital death in the world [...] Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
3 pages, 222 KiB  
Editorial
New Strategies for Treatment of Sepsis
by Antonio Mirijello, Alberto Tosoni and on behalf of the Internal Medicine Sepsis Study Group
Medicina 2020, 56(10), 527; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56100527 - 10 Oct 2020
Cited by 17 | Viewed by 4313
Abstract
Sepsis represents a major global health concern and is one of the most feared complications for hospitalized patients, being the cause, directly or indirectly, of about half of all hospital deaths. According to the last definition, sepsis is a life-threatening organ dysfunction caused [...] Read more.
Sepsis represents a major global health concern and is one of the most feared complications for hospitalized patients, being the cause, directly or indirectly, of about half of all hospital deaths. According to the last definition, sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and defined septic shock as a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to significantly increase mortality. Sepsis is a time-dependent disease and requires a prompt recognition and a standardized treatment. The Special Issue “New Strategies for Treatment of Sepsis” has been thought to connect the experience of physicians involved in the diagnosis, management, and treatment of sepsis at every stage of disease, from emergency departments to general and intensive wards. The focus will be pointed on new approaches to this syndrome, such as early recognition based on clinical features and biomarkers, management in non-ICUs, non-invasive treatment strategies, including non-antimicrobial agents, and, of course, invasive approaches. This Special Issue will highlight the many different facets of sepsis, seen through the eyes of different specialists. We hope to spread the knowledge of a new blueprint for treatment. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)

Research

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11 pages, 676 KiB  
Article
Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit
by Silvia Spoto, Domenica Marika Lupoi, Emanuele Valeriani, Marta Fogolari, Luciana Locorriere, Giuseppina Beretta Anguissola, Giulia Battifoglia, Damiano Caputo, Alessandro Coppola, Sebastiano Costantino, Massimo Ciccozzi and Silvia Angeletti
Medicina 2021, 57(8), 811; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57080811 - 07 Aug 2021
Cited by 18 | Viewed by 2402
Abstract
Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials [...] Read more.
Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer’s instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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9 pages, 613 KiB  
Article
Post-Prescription Audit Plus Beta-D-Glucan Assessment Decrease Echinocandin Use in People with Suspected Invasive Candidiasis
by Rita Murri, Sara Lardo, Alessio De Luca, Brunella Posteraro, Riccardo Torelli, Giulia De Angelis, Francesca Giovannenze, Francesco Taccari, Lucia Pavan, Lucia Parroni, Maurizio Sanguinetti and Massimo Fantoni
Medicina 2021, 57(7), 656; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57070656 - 26 Jun 2021
Cited by 4 | Viewed by 1594
Abstract
Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing [...] Read more.
Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing echinocandin use in persons with suspected invasive candidiasis. Materials and Methods: This is a prospective, pre-post quasi-experimental study of people starting echinocandins for suspected invasive candidiasis. The intervention of the study included review of each echinocandin prescription and discontinuation of treatment if a very low probability of fungal disease or a negative BDG value were found. Pre-intervention data were compared with the intervention phase. The primary outcome of the study was the duration of echinocandin therapy. Secondary outcomes were length of hospital stay and mortality. Results: Ninety-two echinocandin prescriptions were reviewed, 49 (53.3%) in the pre-intervention phase and 43 (46.7%) in the intervention phase. Discontinuation of antifungal therapy was possible in 21 of the 43 patients in the intervention phase (48.8%). The duration of echinocandin therapy was 7.4 (SD 4.7) in the pre-intervention phase, 4.1 days (SD 2.9) in persons undergoing the intervention, and 8.6 (SD 7.3) in persons in whom the intervention was not feasible (p at ANOVA = 0.016). Length of stay and mortality did not differ between pre-intervention and intervention phases. Conclusions: An intervention based on pre-prescription restriction and post-prescription audit when combined with BDG measurement is effective in optimizing antifungal therapy by significantly reducing excessive treatment duration. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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8 pages, 631 KiB  
Article
Recognition in Emergency Department of Septic Patients at Higher Risk of Death: Beware of Patients without Fever
by Emanuela Sozio, Alessio Bertini, Giacomo Bertolino, Francesco Sbrana, Andrea Ripoli, Fabio Carfagna, Alessandro Giacinta, Bruno Viaggi, Simone Meini, Lorenzo Ghiadoni and Carlo Tascini
Medicina 2021, 57(6), 612; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57060612 - 12 Jun 2021
Cited by 3 | Viewed by 2082
Abstract
Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of [...] Read more.
Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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7 pages, 293 KiB  
Article
Delta-Procalcitonin and Vitamin D Can Predict Mortality of Internal Medicine Patients with Microbiological Identified Sepsis
by Alberto Tosoni, Anthony Cossari, Mattia Paratore, Michele Impagnatiello, Giovanna Passaro, Carla Vincenza Vallone, Vincenzo Zaccone, Antonio Gasbarrini, Giovanni Addolorato, Salvatore De Cosmo, Antonio Mirijello and on behalf of the Internal Medicine Sepsis Study Group
Medicina 2021, 57(4), 331; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57040331 - 01 Apr 2021
Cited by 8 | Viewed by 1659
Abstract
Background: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association [...] Read more.
Background: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. Objectives: To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. Methods: This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Results: Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: p = 0.525; 90-days: p = 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: p = 0.002; 90-days: p < 0.001). Delta-PCT was associated with a lower 28-days (p = 0.007; OR = 0.12, 95%CI 0.02–0.46) and 90-days mortality (p = 0.001; OR = 0.17, 95%CI 0.06–0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: p = 0.047; 90-days: p = 0.049). Severe vitamin D deficiency was associated with a higher 28-days (p = 0.058; OR = 3.95, 95%CI 1.04–19.43) and 90-days mortality (p = 0.054; OR = 2.94, 95%CI 1.00–9.23). Conclusions: Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
8 pages, 285 KiB  
Article
The Role of Early Procalcitonin Determination in the Emergency Departiment in Adults Hospitalized with Fever
by Marcello Covino, Antonella Gallo, Massimo Montalto, Giuseppe De Matteis, Maria Livia Burzo, Benedetta Simeoni, Rita Murri, Marcello Candelli, Veronica Ojetti and Francesco Franceschi
Medicina 2021, 57(2), 179; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57020179 - 19 Feb 2021
Cited by 7 | Viewed by 2274
Abstract
Background and Objectives: Fever is one of the most common presenting complaints in the Emergency Department (ED). The role of serum procalcitonin (PCT) determination in the ED evaluation of adults presenting with fever is still debated. The aim of this study was to [...] Read more.
Background and Objectives: Fever is one of the most common presenting complaints in the Emergency Department (ED). The role of serum procalcitonin (PCT) determination in the ED evaluation of adults presenting with fever is still debated. The aim of this study was to evaluate if, in adults presenting to the ED with fever and then hospitalized, the early PCT determination could improve prognosis. Materials and Methods. This is a retrospective, mono-centric study, conducted over a 10-year period (2009–2018). We analyzed consecutive patients ≥18 years admitted to ED with fever and then hospitalized. According to quick sequential organ failure assessment (qSOFA) at admission, we compared patients that had a PCT determination vs. controls. Primary endpoint was overall in-hospital mortality; secondary endpoints were in-hospital length of stay, and mortality in patients with bloodstream infection and acute respiratory infections. Results. The sample included 12,062 patients, median age was 71 years and 55.1% were men. In patients with qSOFA ≥ 2 overall mortality was significantly lower if they had a PCT-guided management in ED, (20.5% vs. 26.5%; p = 0.046). In the qSOFA < 2 group the mortality was not significantly different in PCT patients, except for those with a final diagnosis of bloodstream infection. Conclusions. Among adults hospitalized with fever, the PCT evaluation at ED admission was not associated with better outcomes, with the possible exception of patients affected by bloodstream infections. However, in febrile patients presenting to the ED with qSOFA ≥ 2, the early PCT evaluation could improve the overall in-hospital survival. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
14 pages, 1725 KiB  
Article
Usefulness of Antioxidants as Adjuvant Therapy for Septic Shock: A Randomized Clinical Trial
by Alfredo Aisa-Alvarez, María Elena Soto, Verónica Guarner-Lans, Gilberto Camarena-Alejo, Juvenal Franco-Granillo, Enrique A. Martínez-Rodríguez, Ricardo Gamboa Ávila, Linaloe Manzano Pech and Israel Pérez-Torres
Medicina 2020, 56(11), 619; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56110619 - 17 Nov 2020
Cited by 32 | Viewed by 4814
Abstract
Background and objectives: Oxidative stress (OS) participates in the pathophysiology of septic shock, which leads to multiple organ failure (MOF), ischemia-reperfusion injury, and acute respiratory distress syndrome. Therefore, antioxidants have been proposed as therapy. Here, we evaluated the effect of antioxidant treatments in [...] Read more.
Background and objectives: Oxidative stress (OS) participates in the pathophysiology of septic shock, which leads to multiple organ failure (MOF), ischemia-reperfusion injury, and acute respiratory distress syndrome. Therefore, antioxidants have been proposed as therapy. Here, we evaluated the effect of antioxidant treatments in patients with septic shock with MOF and determined levels OS before and after treatment. This study was a randomized, controlled, triple-masked, and with parallel assignment clinical trial with a control group without treatment. Materials and Methods: It included 97 patients of either sex with septic shock. 5 treatments were used each in an independent group of 18 patients. Group 1 received vitamin C (Vit C), group 2 vitamin E (Vit E), group 3 n-acetylcysteine (NAC), group 4 melatonin (MT), and group 5 served as control. All antioxidants were administered orally or through a nasogastric tube for five days as an adjuvant to the standard therapy. Results: The results showed that all patients presented MOF due to sepsis upon admission and that the treatment decreased it (p = 0.007). The antioxidant treatment with NAC increased the total antioxidant capacity (p < 0.05). The patients that received Vit C had decreased levels of the nitrate and nitrite ratio (p < 0.01) and C-reactive protein levels (p = 0.04). Procalcitonin levels were reduced by Vit E (p = 0.04), NAC (p = 0.001), and MT (p = 0.04). Lipid-peroxidation was reduced in patients that received MT (p = 0.04). Conclusions: In conclusion, antioxidant therapy associated with standard therapy reduces MOF, OS, and inflammation in patients with septic shock. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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Review

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7 pages, 281 KiB  
Review
Proadrenomedullin in Sepsis and Septic Shock: A Role in the Emergency Department
by Andrea Piccioni, Angela Saviano, Sara Cicchinelli, Federico Valletta, Michele Cosimo Santoro, Tommaso de Cunzo, Christian Zanza, Yaroslava Longhitano, Gianluca Tullo, Pietro Tilli, Marcello Candelli, Marcello Covino and Francesco Franceschi
Medicina 2021, 57(9), 920; https://doi.org/10.3390/medicina57090920 - 01 Sep 2021
Cited by 19 | Viewed by 3323
Abstract
Sepsis and septic shock represent a leading cause of mortality in the Emergency Department (ED) and in the Intensive Care Unit (ICU). For these life-threating conditions, different diagnostic and prognostic biomarkers have been studied. Proadrenomedullin (MR-proADM) is a biomarker that can predict organ [...] Read more.
Sepsis and septic shock represent a leading cause of mortality in the Emergency Department (ED) and in the Intensive Care Unit (ICU). For these life-threating conditions, different diagnostic and prognostic biomarkers have been studied. Proadrenomedullin (MR-proADM) is a biomarker that can predict organ damage and the risk of imminent death in patients with septic shock, as shown by a large amount of data in the literature. The aim of our narrative review is to evaluate the role of MR-proADM in the context of Emergency Medicine and to summarize the current knowledge of MR-proADM as a serum indicator that is useful in the Emergency Department (ED) to determine an early diagnosis and to predict the long-term mortality of patients with sepsis and septic shock. We performed an electronic literature review to investigate the role of MR-proADM in sepsis and septic shock in the context of ED. We searched papers on PubMed®, Cochrane®, UptoDate®, and Web of Science® that had been published in the last 10 years. Data extracted from this literature review are not conclusive, but they show that MR-proADM may be helpful as a prognostic biomarker to stratify the mortality risk in cases of sepsis and septic shock with different degrees of organ damage, guiding emergency physicians in the diagnosis and the succeeding therapeutic workup. Sepsis and septic shock are conditions of high complexity and have a high risk of mortality. In the ED, early diagnosis is crucial in order to provide an early treatment and to improve patient survival. Diagnosis and prognosis are often the result of a combination of several tests. In our opinion, testing for MR-proADM directly in the ED could contribute to improving the prognostic assessment of patients, facilitating the subsequent clinical management and intensive treatment by the emergency physicians, but more studies are needed to confirm these results. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
11 pages, 633 KiB  
Review
Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review
by Andrea Piccioni, Michele Cosimo Santoro, Tommaso de Cunzo, Gianluca Tullo, Sara Cicchinelli, Angela Saviano, Federico Valletta, Marco Maria Pascale, Marcello Candelli, Marcello Covino and Francesco Franceschi
Medicina 2021, 57(8), 770; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57080770 - 29 Jul 2021
Cited by 25 | Viewed by 4076
Abstract
The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on [...] Read more.
The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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10 pages, 1337 KiB  
Review
Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile
by Giuseppe Bertozzi, Aniello Maiese, Giovanna Passaro, Alberto Tosoni, Antonio Mirijello, Stefania De Simone, Benedetta Baldari, Luigi Cipolloni and Raffaele La Russa
Medicina 2021, 57(6), 638; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57060638 - 20 Jun 2021
Cited by 10 | Viewed by 4226
Abstract
Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. [...] Read more.
Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic “neutropenic enterocolitis and sepsis” appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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11 pages, 498 KiB  
Review
Immune Modulation in Critically Ill Septic Patients
by Salvatore Lucio Cutuli, Simone Carelli, Domenico Luca Grieco and Gennaro De Pascale
Medicina 2021, 57(6), 552; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57060552 - 31 May 2021
Cited by 13 | Viewed by 2322
Abstract
Sepsis is triggered by infection-induced immune alteration and may be theoretically improved by pharmacological and extracorporeal immune modulating therapies. Pharmacological immune modulation may have long lasting clinical effects, that may even worsen patient-related outcomes. On the other hand, extracorporeal immune modulation allows short-term [...] Read more.
Sepsis is triggered by infection-induced immune alteration and may be theoretically improved by pharmacological and extracorporeal immune modulating therapies. Pharmacological immune modulation may have long lasting clinical effects, that may even worsen patient-related outcomes. On the other hand, extracorporeal immune modulation allows short-term removal of inflammatory mediators from the bloodstream. Although such therapies have been widely used in clinical practice, the role of immune modulation in critically ill septic patients remains unclear and little evidence supports the role of immune modulation in this clinical context. Accordingly, further research should be carried out by an evidence-based and personalized approach in order to improve the management of critically ill septic patients. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
13 pages, 1157 KiB  
Review
Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have Learned and What We Want to Know in Future Trials
by Matteo Rossetti, Gennaro Martucci, Christina Starchl and Karin Amrein
Medicina 2021, 57(5), 419; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57050419 - 26 Apr 2021
Cited by 13 | Viewed by 4140
Abstract
Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2–3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, [...] Read more.
Sepsis remains the leading cause of mortality in hospitalized patients, contributing to 1 in every 2–3 deaths. From a pathophysiological view, in the recent definition, sepsis has been defined as the result of a complex interaction between host response and the infecting organism, resulting in life-threatening organ dysfunction, depending on microcirculatory derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The high energy expenditure driven by a high metabolic state induced by the host response may rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal energy homeostasis, free radical damage, and immune system derangement. In critically ill patients, micronutrients are still relegated to an ancillary role in the whole treatment, and always put in a second-line place or, frequently, neglected. Only some micronutrients have attracted the attention of a wider audience, and some trials, even large ones, have tested their use, with controversial results. The present review will address this topic, including the recent advancement in the study of vitamin D and protocols based on vitamin C and other micronutrients, to explore an update in the setting of sepsis, gain some new insights applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the potential role of micronutrients that will be helpful in future dedicated trials. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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Case Report
Successful Treatment of Klebsiella pneumoniae NDM Sepsis and Intestinal Decolonization with Ceftazidime/Avibactam Plus Aztreonam Combination in a Patient with TTP Complicated by SARS-CoV-2 Nosocomial Infection
by Francesco Perrotta and Marco Paolo Perrini
Medicina 2021, 57(5), 424; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57050424 - 28 Apr 2021
Cited by 8 | Viewed by 2379
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Among them, metallo-β-lactamases (MBLs)-producing Klebsiella pneumoniae are of global concern today. The ceftazidime/avibactam combination and the ceftazidime/avibactam + aztreonam combination currently represent [...] Read more.
Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Among them, metallo-β-lactamases (MBLs)-producing Klebsiella pneumoniae are of global concern today. The ceftazidime/avibactam combination and the ceftazidime/avibactam + aztreonam combination currently represent the most promising antibiotic strategies to stave off these kinds of infections. We describe the case of a patient affected by thrombotic thrombocytopenic purpura (TTP) admitted in our ICU after developing a hospital-acquired SARS-CoV-2 interstitial pneumonia during his stay in the hematology department. His medical conditions during his ICU stay were further complicated by a K. Pneumoniae NDM sepsis. To our knowledge, the patient had no risk factors for multidrug-resistant bacteria exposure or contamination during his stay in the hematology department. During his stay in the ICU, we treated the sepsis with a combination therapy of ceftazidime/avibactam + aztreonam. The therapy solved his septic state, allowing for a progressive improvement in his general condition. Moreover, we noticed that the negativization of the hemocultures was also associated to a decontamination of his known rectal colonization. The ceftazidime/avibactam + aztreonam treatment could not only be a valid therapeutic option for these kinds of infections, but it could also be considered as a useful tool in selected patients’ intestinal decolonizations. Full article
(This article belongs to the Special Issue New Strategies for Treatment of Sepsis)
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