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Microorganisms
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Advances in Bacterial Sepsis
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Advances in Bacterial Sepsis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 29179

Special Issue Editors

Dr. Narcis Ioan Popescu

E-Mail Website
Guest Editor
Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
Interests: innate immunity; infection; sepsis; humoral immunity; coagulation; immunothrombosis; complement; inflammation
Dr. Houssein Youness

E-Mail Website
Guest Editor
Section of Pulmonary, Critical Care and Sleep Medicine, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA
Interests: lung cancer; diagnosis; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sepsis is a life-threatening pathology characterized by a dysregulated immune response to an invading pathogen which injures the host’s tissues and organs. Sepsis is a major global health threat and an intermediate cause of health loss contributing to roughly 20% of deaths worldwide. While any infection may lead to sepsis, bacterial infections are the most prevalent cause of sepsis and sepsis-related deaths in both children and adults. Antimicrobials and the mitigation of detrimental host responses have steadily improved sepsis mortality in the last couple decades; however, the number of sepsis-related deaths remains unacceptably high. Unfortunately, the expansion of antibiotic resistance is expected to significantly hamper our therapeutic toolkit against bacterial infections and sepsis in the near future. Therefore, further studies are needed to understand the mechanisms underlying pathologic progressions to sepsis, identify predictive biomarkers, and establish algorithms to stratify patients and aid clinical decisions in sepsis.

The Special Issue “Advances in Bacterial Sepsis” aims to assemble a collection of research articles and reviews that explore the molecular mechanisms behind bacteria and host interactions, the infection-driven immunological impairment promoting sepsis, and the subsequent multiple organ dysfunction and post-sepsis sequelae in survivors. Brief perspectives that challenge current paradigms or initiate debates on new therapeutic strategies are also welcomed.

Dr. Narcis Ioan Popescu
Dr. Houssein Youness
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at mdpi.longhoe.net 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. Microorganisms is an international peer-reviewed open access monthly 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 2700 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

  • bacterial infection
  • sepsis
  • septic shock
  • multiple-organ dysfunction
  • innate immunity
  • humoral immunity
  • inflammation
  • complement
  • immunothrombosis
  • adaptive immunity

Published Papers (6 papers)

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Research

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9 pages, 261 KiB  
Communication
Clinical Utility of the FilmArray® Blood Culture Identification (BCID) Panel for the Diagnosis of Neonatal Sepsis
by María Caunedo-Jiménez, Belén Fernández-Colomer, Jonathan Fernández-Suárez, Rosa Patricia Arias-Llorente, Sonia Lareu-Vidal, Laura Mantecón-Fernández, Gonzalo Solís-Sánchez and Marta Suárez-Rodríguez
Microorganisms 2023, 11(3), 732; https://doi.org/10.3390/microorganisms11030732 - 12 Mar 2023
Cited by 3 | Viewed by 1494
Abstract
This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture [...] Read more.
This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a two-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 h of blood culture incubation (IQR 8–20), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which were Streptococcus epidermidis in neonates with LOS, and there was one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay. Full article
(This article belongs to the Special Issue Advances in Bacterial Sepsis)
12 pages, 275 KiB  
Article
Early Diagnosis of Late-Onset Neonatal Sepsis Using a Sepsis Prediction Score
by Georgia Anna Sofouli, Asimina Tsintoni, Sotirios Fouzas, Aggeliki Vervenioti, Despoina Gkentzi and Gabriel Dimitriou
Microorganisms 2023, 11(2), 235; https://doi.org/10.3390/microorganisms11020235 - 17 Jan 2023
Cited by 8 | Viewed by 3213
Abstract
Sepsis represents a common cause of morbidity in the Neonatal Intensive Care Unit (NICU). Our objective was to assess the value of clinical and laboratory parameters in predicting septicemia (positive blood culture) in NICU infants. In the first part of the present study [...] Read more.
Sepsis represents a common cause of morbidity in the Neonatal Intensive Care Unit (NICU). Our objective was to assess the value of clinical and laboratory parameters in predicting septicemia (positive blood culture) in NICU infants. In the first part of the present study (derivation cohort) we retrospectively reviewed the clinical files of 120 neonates with symptoms of suspected sepsis and identified clinical and laboratory parameters associated with proven sepsis on the day the blood culture was taken, as well as 24 h and 48 h earlier. These parameters were combined into a sepsis prediction score (SPS). Subsequently (validation study), we prospectively validated the performance of the SPS in a cohort of 145 neonates. The identified parameters were: temperature instability, platelet count < 150,000/mm3, feeding volume decrease > 20%, changes in blood glucose > 50%, CRP > 1 mg/dL, circulatory and respiratory deterioration. In the retrospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 82.54% sensitivity, 85.96% specificity, 5.88 PLR (Positive Likelihood Ratio), 0.20 NLR (Negative Likelihood Ratio), 86.67% PPV (Positive Predictive Value), 81.67% NPV (Negative Predictive Value) and 84.17% accuracy. In the prospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 76.60% sensitivity, 72.55% specificity, 2.79 PLR, 0.32 NLR, 83.72% PPV, 62.71% NPV and 75.17% accuracy. We concluded that this combination of clinical and laboratory parameters may assist in the prediction of septicemia in NICUs. Full article
(This article belongs to the Special Issue Advances in Bacterial Sepsis)
13 pages, 1155 KiB  
Article
Gram-Positive Bacteria Cell Wall Peptidoglycan Polymers Activate Human Dendritic Cells to Produce IL-23 and IL-1β and Promote TH17 Cell Differentiation
by Sean Turner, Brent Raisley, Kimberly Roach, Sandra Bajaña, Melissa E. Munroe, Judith A. James, K. Mark Coggeshall and Susan Kovats
Microorganisms 2023, 11(1), 173; https://doi.org/10.3390/microorganisms11010173 - 10 Jan 2023
Cited by 7 | Viewed by 2325
Abstract
Gram-positive bacterial infections are a major cause of organ failure and mortality in sepsis. Cell wall peptidoglycan (PGN) is shed during bacterial replication, and Bacillus anthracis PGN promotes a sepsis-like pathology in baboons. Herein, we determined the ability of polymeric Bacillus anthracis PGN [...] Read more.
Gram-positive bacterial infections are a major cause of organ failure and mortality in sepsis. Cell wall peptidoglycan (PGN) is shed during bacterial replication, and Bacillus anthracis PGN promotes a sepsis-like pathology in baboons. Herein, we determined the ability of polymeric Bacillus anthracis PGN free from TLR ligands to shape human dendritic cell (DC) responses that are important for the initiation of T cell immunity. Monocyte-derived DCs from healthy donors were incubated with PGN polymers isolated from Bacillus anthracis and Staphylococcus aureus. PGN activated the human DCs, as judged by the increased expression of surface HLA-DR, CD83, the T cell costimulatory molecules CD40 and CD86, and the chemokine receptor CCR7. PGN elicited the DC production of IL-23, IL-6, and IL-1β but not IL-12p70. The PGN-stimulated DCs induced the differentiation of naïve allogeneic CD4+ T cells into T helper (TH) cells producing IL-17 and IL-21. Notably, the DCs from a subset of donors did not produce significant levels of IL-23 and IL-1β upon PGN stimulation, suggesting that common polymorphisms in immune response genes regulate the PGN response. In sum, purified PGN is a highly stimulatory cell wall component that activates human DCs to secrete proinflammatory cytokines and promote the differentiation of TH17 cells that are important for neutrophil recruitment in extracellular bacterial infections. Full article
(This article belongs to the Special Issue Advances in Bacterial Sepsis)
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Review

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28 pages, 2029 KiB  
Review
Management of Sepsis and Septic Shock: What Have We Learned in the Last Two Decades?
by Shiwani Kamath, Hiba Hammad Altaq and Tony Abdo
Microorganisms 2023, 11(9), 2231; https://doi.org/10.3390/microorganisms11092231 - 4 Sep 2023
Cited by 7 | Viewed by 14255
Abstract
Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two [...] Read more.
Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two decades, the definition of sepsis has evolved to improve early sepsis recognition and screening, standardize the terms used to describe sepsis and highlight its association with organ dysfunction and higher mortality. The early 2000s witnessed the birth of early goal-directed therapy (EGDT), which showed a dramatic reduction in mortality leading to its wide adoption, and the surviving sepsis campaign (SSC), which has been instrumental in develo** and updating sepsis guidelines over the last 20 years. Outside of early fluid resuscitation and antibiotic therapy, sepsis management has transitioned to a less aggressive approach over the last few years, shying away from routine mixed venous oxygen saturation and central venous pressure monitoring and excessive fluids resuscitation, inotropes use, and red blood cell transfusions. Peripheral vasopressor use was deemed safe and is rising, and resuscitation with balanced crystalloids and a restrictive fluid strategy was explored. This review will address some of sepsis management’s most important yet controversial components and summarize the available evidence from the last two decades. Full article
(This article belongs to the Special Issue Advances in Bacterial Sepsis)
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23 pages, 727 KiB  
Review
Clinical Sepsis Phenotypes in Critically Ill Patients
by Georgios Papathanakos, Ioannis Andrianopoulos, Menelaos Xenikakis, Athanasios Papathanasiou, Despoina Koulenti, Stijn Blot and Vasilios Koulouras
Microorganisms 2023, 11(9), 2165; https://doi.org/10.3390/microorganisms11092165 - 27 Aug 2023
Cited by 4 | Viewed by 4628
Abstract
Sepsis, defined as the life-threatening dysregulated host response to an infection leading to organ dysfunction, is considered as one of the leading causes of mortality worldwide, especially in intensive care units (ICU). Moreover, sepsis remains an enigmatic clinical syndrome, with complex pathophysiology incompletely [...] Read more.
Sepsis, defined as the life-threatening dysregulated host response to an infection leading to organ dysfunction, is considered as one of the leading causes of mortality worldwide, especially in intensive care units (ICU). Moreover, sepsis remains an enigmatic clinical syndrome, with complex pathophysiology incompletely understood and a great heterogeneity both in terms of clinical expression, patient response to currently available therapeutic interventions and outcomes. This heterogeneity proves to be a major obstacle in our quest to deliver improved treatment in septic critical care patients; thus, identification of clinical phenotypes is absolutely necessary. Although this might be seen as an extremely difficult task, nowadays, artificial intelligence and machine learning techniques can be recruited to quantify similarities between individuals within sepsis population and differentiate them into distinct phenotypes regarding not only temperature, hemodynamics or type of organ dysfunction, but also fluid status/responsiveness, trajectories in ICU and outcome. Hopefully, we will eventually manage to determine both the subgroup of septic patients that will benefit from a therapeutic intervention and the correct timing of applying the intervention during the disease process. Full article
(This article belongs to the Special Issue Advances in Bacterial Sepsis)
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17 pages, 1636 KiB  
Review
Antimicrobial Exposure in Critically Ill Patients with Sepsis-Associated Multi-Organ Dysfunction Requiring Extracorporeal Organ Support: A Narrative Review
by Salvatore Lucio Cutuli, Laura Cascarano, Paolo Lazzaro, Eloisa Sofia Tanzarella, Gabriele Pintaudi, Domenico Luca Grieco, Gennaro De Pascale and Massimo Antonelli
Microorganisms 2023, 11(2), 473; https://doi.org/10.3390/microorganisms11020473 - 13 Feb 2023
Cited by 5 | Viewed by 2162
Abstract
Sepsis is a leading cause of disability and mortality worldwide. The pathophysiology of sepsis relies on the maladaptive host response to pathogens that fosters unbalanced organ crosstalk and induces multi-organ dysfunction, whose severity was directly associated with mortality. In septic patients, etiologic interventions [...] Read more.
Sepsis is a leading cause of disability and mortality worldwide. The pathophysiology of sepsis relies on the maladaptive host response to pathogens that fosters unbalanced organ crosstalk and induces multi-organ dysfunction, whose severity was directly associated with mortality. In septic patients, etiologic interventions aiming to reduce the pathogen load via appropriate antimicrobial therapy and the effective control of the source infection were demonstrated to improve clinical outcomes. Nonetheless, extracorporeal organ support represents a complementary intervention that may play a role in mitigating life-threatening complications caused by sepsis-associated multi-organ dysfunction. In this setting, an increasing amount of research raised concerns about the risk of suboptimal antimicrobial exposure in critically ill patients with sepsis, which may be worsened by the concomitant delivery of extracorporeal organ support. Accordingly, several strategies have been implemented to overcome this issue. In this narrative review, we discussed the pharmacokinetic features of antimicrobials and mechanisms that may favor drug removal during renal replacement therapy, coupled plasma filtration and absorption, therapeutic plasma exchange, hemoperfusion, extracorporeal CO2 removal and extracorporeal membrane oxygenation. We also provided an overview of evidence-based strategies that may help the physician to safely prescribe effective antimicrobial doses in critically ill patients with sepsis-associated multi-organ dysfunction who receive extracorporeal organ support. Full article
(This article belongs to the Special Issue Advances in Bacterial Sepsis)
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