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10 pages, 1546 KiB

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The Role of the Pancreatic Stone Protein in Predicting Intra-Abdominal Infection-Related Complications: A Prospective Observational Single-Center Cohort Study

by Christos Michailides, Maria Lagadinou, Themistoklis Paraskevas, Konstantinos Papantoniou, Michael Kavvousanos, Achilleas Vasileiou, Konstantinos Thomopoulos, Dimitrios Velissaris and Markos Marangos

Microorganisms 2023, 11(10), 2579; https://doi.org/10.3390/microorganisms11102579 - 17 Oct 2023

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Abstract

Background: The Pancreatic Stone Protein (PSP) is an acute-phase protein that is mainly secreted by pancreatic cells in response to stress. The current literature supports its use as a predictor of sepsis. Its prognostic role has recently been evaluated in a point-of-care setting, [...] Read more.

Background: The Pancreatic Stone Protein (PSP) is an acute-phase protein that is mainly secreted by pancreatic cells in response to stress. The current literature supports its use as a predictor of sepsis. Its prognostic role has recently been evaluated in a point-of-care setting, mostly in high-risk patients. We conducted a prospective observational cohort study to evaluate its utility in the prognosis of patients admitted to the hospital with a diagnosis of intra-abdominal infection. Methods: Adult patients consecutively admitted to the Internal Medicine Department of the University Hospital of Patras, Greece, with a diagnosis of intra-abdominal infection were enrolled. PSP levels were measured within 24 h of admission in whole blood. Results: a total of 40 patients were included after being diagnosed with IAI. PSP was used as an independent predictive factor for sepsis after adjusting for age with OR = 7.888 (95% CI: 1.247–49.890). PSP also predicted readmission and the need for treatment escalation (p: <0.01) and was an excellent prognostic factor regarding these outcomes (AUC = 0.899, 95% CI: 0.794–1.0, and AUC = 0.862, 95% CI: 0.748–0.976, respectively). PSP also proved superior to CRP, ferritin, and fibrinogen in sepsis diagnosis, treatment escalation, and readmission prediction with an AUC of 0.862, 0.698, and 0.899, respectively. Conclusions: PSP can predict unfavorable outcomes, such as sepsis development, readmission, and the need for treatment escalation among patients with intra-abdominal infections. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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11 pages, 893 KiB

Open AccessArticle

Influence of Sepsis on the Middle-Term Outcomes for Urinary Tract Infections in Elderly People

by Arturo Artero, Ian López-Cruz, Juan Alberola, José María Eiros, Elena Resa, Laura Piles and Manuel Madrazo

Microorganisms 2023, 11(8), 1959; https://doi.org/10.3390/microorganisms11081959 - 31 Jul 2023

Cited by 1 | Viewed by 1052

Abstract

Urinary tract infection (UTI) is a common condition that predominantly affects elderly people, who are particularly susceptible to developing sepsis. Previous studies have indicated a detrimental effect of sepsis on short-term outcomes in elderly patients with UTI, but there is a lack of [...] Read more.

Urinary tract infection (UTI) is a common condition that predominantly affects elderly people, who are particularly susceptible to developing sepsis. Previous studies have indicated a detrimental effect of sepsis on short-term outcomes in elderly patients with UTI, but there is a lack of data about the middle-term prognosis. The aim of this study was to investigate the influence of sepsis on the middle-term prognosis of patients aged 65 years or older with complicated community-acquired UTIs. A prospective observational study of patients admitted to a hospital with UTI. We conducted a comparison of epidemiological and clinical variables between septic and nonseptic patients with UTI, as well as their 6-month case-fatality rate. A total of 412 cases were included, 47.8% of them with sepsis. Septic patients were older (83 vs. 80 years, p < 0.001), but did not have more comorbidities. The short-term case-fatality rate was higher in septic patients and this difference persisted at 6 months (34% vs. 18.6%, p = 0.003). Furthermore, age older than 75 years, Barthel index <40 and healthcare-associated UTI were also associated with the middle-term case-fatality rate. In conclusion, the detrimental impact of sepsis is maintained on the middle-term prognosis of elderly patients with UTI. Age, functional status and healthcare-associated UTIs also play significant roles in shaping patient outcomes. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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16 pages, 1916 KiB

Open AccessArticle

Virulence Factor Genes in Invasive Escherichia coli Are Associated with Clinical Outcomes and Disease Severity in Patients with Sepsis: A Prospective Observational Cohort Study

by Valentino D’Onofrio, Reinoud Cartuyvels, Peter E. A. Messiaen, Ivan Barišić and Inge C. Gyssens

Microorganisms 2023, 11(7), 1827; https://doi.org/10.3390/microorganisms11071827 - 17 Jul 2023

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Abstract

Background: Escherichia coli harbours virulence factors that facilitate the development of bloodstream infections. Studies determining virulence factors in clinical isolates often have limited access to clinical data and lack associations with patient outcome. The goal of this study was to correlate sepsis outcome [...] Read more.

Background: Escherichia coli harbours virulence factors that facilitate the development of bloodstream infections. Studies determining virulence factors in clinical isolates often have limited access to clinical data and lack associations with patient outcome. The goal of this study was to correlate sepsis outcome and virulence factors of clinical E. coli isolates in a large cohort. Methods: Patients presenting at the emergency department whose blood cultures were positive for E. coli were prospectively included. Clinical and laboratory parameters were collected at admission. SOFA-score was calculated to determine disease severity. Patient outcomes were in-hospital mortality and ICU admission. Whole genome sequencing was performed for E. coli isolates and virulence genes were detected using the VirulenceFinder database. Results: In total, 103 E. coli blood isolates were sequenced. Isolates had six to 41 virulence genes present. One virulence gene, kpsMII_K23, a K1 capsule group 2 of E. coli type K23, was significantly more present in isolates of patients who died. kpsMII_K23 and cvaC (Microcin C) were significantly more frequent in isolates of patients who were admitted to the ICU. Fourteen virulence genes (mchB, mchC, papA_fsiA_F16, sat, senB, iucC, iutA, iha, sfaD, cnf1, focG, vat, cldB, and mcmA) significantly differed between patients with and without sepsis. Conclusions: Microcins, toxins, and fimbriae were associated with disease severity. Adhesins and iron uptake proteins seemed to be protective. Two genes were associated with worse clinical outcome. These findings contribute to a better understanding of host-pathogen interactions and could help identifying patients most at risk for a worse outcome. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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13 pages, 505 KiB

Open AccessArticle

Risk Factors and the Impact of Multidrug-Resistant Bacteria on Community-Acquired Urinary Sepsis

by Manuel Madrazo, Ian López-Cruz, Laura Piles, Sofía Viñola, Juan Alberola, José María Eiros and Arturo Artero

Microorganisms 2023, 11(5), 1278; https://doi.org/10.3390/microorganisms11051278 - 13 May 2023

Cited by 1 | Viewed by 1193

Abstract

Risk factors for multidrug-resistant bacteria (MDRB) in nosocomial urinary tract infection (UTI) have been widely studied. However, these risk factors have not been analyzed in community-acquired urinary sepsis (US), nor have its outcomes been studied. The aim of our study is to determine [...] Read more.

Risk factors for multidrug-resistant bacteria (MDRB) in nosocomial urinary tract infection (UTI) have been widely studied. However, these risk factors have not been analyzed in community-acquired urinary sepsis (US), nor have its outcomes been studied. The aim of our study is to determine risk factors for MDRB in community-acquired US and its influence on outcomes. Prospective observational study of patients with community-acquired US admitted to a university hospital. We compared epidemiological and clinical variables and outcomes of US due to MDRB and non-MDRB. Independent risk factors for MDRB were analyzed using logistic regression. A total of 193 patients were included, 33.7% of them with US due to MDRB. The median age of patients was 82 years. Hospital mortality was 17.6%, with no difference between the MDRB and non-MDRB groups. The length of hospital stay was 5 (4–8) days, with a non-significant tendency to longer hospital stays in the MDRB group (6 (4–10) vs. 5 (4–8) days, p = 0.051). Healthcare-associated US was found to be an independent risk factor for MDR bacteria by multivariate analysis. In conclusion, the impact of MDR bacteria on the outcomes of community-acquired urinary sepsis was mild. Healthcare-associated US was an independent risk factor for MDR bacteria. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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9 pages, 605 KiB

Open AccessArticle

Potential of Molecular Culture in Early Onset Neonatal Sepsis Diagnosis: A Proof of Principle Study

by Thomas Dierikx, Andries Budding, Martine Bos, Henriëtte van Laerhoven, Sophie van der Schoor, Hendrik Niemarkt, Marc Benninga, Anton van Kaam, Douwe Visser and Tim de Meij

Microorganisms 2023, 11(4), 960; https://doi.org/10.3390/microorganisms11040960 - 7 Apr 2023

Cited by 3 | Viewed by 1523

Abstract

Delay in the time-to-positivity of a peripheral blood culture (PBC), the gold standard for early onset neonatal sepsis (EOS) diagnosis, has resulted in excessive use of antibiotics. In this study, we evaluate the potential of the rapid Molecular Culture (MC) assay for quick [...] Read more.

Delay in the time-to-positivity of a peripheral blood culture (PBC), the gold standard for early onset neonatal sepsis (EOS) diagnosis, has resulted in excessive use of antibiotics. In this study, we evaluate the potential of the rapid Molecular Culture (MC) assay for quick EOS diagnosis. In the first part of this study, known positive and spiked blood samples were used to assess the performance of MC. In the in vivo clinical study, the second part of this study, all infants receiving antibiotics for suspicion of EOS were included. At initial EOS suspicion, a blood sample was collected for PBC and MC. MC was able to detect bacteria present in the spiked samples even when the bacterial load was low. In the clinical study, MC was positive in one infant with clinical EOS (Enterococcus faecalis) that was not detected by PBC. Additionally, MC was positive in two infants without clinical sepsis (Streptococcus mitis and multiple species), referred to as contamination. The other 37 samples were negative both by MC and PBC. MC seems to be able to detect bacteria even when the bacterial load is low. The majority of MC and PBC results were comparable and the risk for contamination and false positive MC results seems to be limited. Since MC can generate results within 4 h following sampling compared with 36–72 h in PBC, MC may have the potential to replace conventional PBC in EOS diagnostics in order to guide clinicians on when to discontinue antibiotic therapy several hours after birth. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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15 pages, 2611 KiB

Open AccessArticle

From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis

by Christina Hartwig, Susanne Drechsler, Yevhen Vainshtein, Madeline Maneth, Theresa Schmitt, Monika Ehling-Schulz, Marcin Osuchowski and Kai Sohn

Microorganisms 2023, 11(3), 627; https://doi.org/10.3390/microorganisms11030627 - 28 Feb 2023

Cited by 2 | Viewed by 1629

Abstract

Abdominal sepsis triggers the transition of microorganisms from the gut to the peritoneum and bloodstream. Unfortunately, there is a limitation of methods and biomarkers to reliably study the emergence of pathobiomes and to monitor their respective dynamics. Three-month-old CD-1 female mice underwent cecal [...] Read more.

Abdominal sepsis triggers the transition of microorganisms from the gut to the peritoneum and bloodstream. Unfortunately, there is a limitation of methods and biomarkers to reliably study the emergence of pathobiomes and to monitor their respective dynamics. Three-month-old CD-1 female mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Serial and terminal endpoint specimens were collected for fecal, peritoneal lavage, and blood samples within 72 h. Microbial species compositions were determined by NGS of (cell-free) DNA and confirmed by microbiological cultivation. As a result, CLP induced rapid and early changes of gut microbial communities, with a transition of pathogenic species into the peritoneum and blood detected at 24 h post-CLP. NGS was able to identify pathogenic species in a time course-dependent manner in individual mice using cfDNA from as few as 30 microliters of blood. Absolute levels of cfDNA from pathogens changed rapidly during acute sepsis, demonstrating its short half-life. Pathogenic species and genera in CLP mice significantly overlapped with pathobiomes from septic patients. The study demonstrated that pathobiomes serve as reservoirs following CLP for the transition of pathogens into the bloodstream. Due to its short half-life, cfDNA can serve as a precise biomarker for pathogen identification in blood. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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Review

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20 pages, 1349 KiB

Open AccessReview

Multi-Omics Endotypes in ICU Sepsis-Induced Immunosuppression

by Alexis Garduno, Rachael Cusack, Marc Leone, Sharon Einav and Ignacio Martin-Loeches

Microorganisms 2023, 11(5), 1119; https://doi.org/10.3390/microorganisms11051119 - 25 Apr 2023

Cited by 3 | Viewed by 2467

Abstract

It is evident that the admission of some patients with sepsis and septic shock to hospitals is occurring late in their illness, which has contributed to the increase in poor outcomes and high fatalities worldwide across age groups. The current diagnostic and monitoring [...] Read more.

It is evident that the admission of some patients with sepsis and septic shock to hospitals is occurring late in their illness, which has contributed to the increase in poor outcomes and high fatalities worldwide across age groups. The current diagnostic and monitoring procedure relies on an inaccurate and often delayed identification by the clinician, who then decides the treatment upon interaction with the patient. Initiation of sepsis is accompanied by immune system paralysis following “cytokine storm”. The unique immunological response of each patient is important to define in terms of subtyping for therapy. The immune system becomes activated in sepsis to produce interleukins, and endothelial cells express higher levels of adhesion molecules. The proportions of circulating immune cells change, reducing regulatory cells and increasing memory cells and killer cells, having long-term effects on the phenotype of CD8 T cells, HLA-DR, and dysregulation of microRNA. The current narrative review seeks to highlight the potential application of multi-omics data integration and immunological profiling at the single-cell level to define endotypes in sepsis and septic shock. The review will consider the parallels and immunoregulatory axis between cancer and immunosuppression, sepsis-induced cardiomyopathy, and endothelial damage. Second, the added value of transcriptomic-driven endotypes will be assessed through inferring regulatory interactions in recent clinical trials and studies reporting gene modular features that inform continuous metrics measuring clinical response in ICU, which can support the use of immunomodulating agents. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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16 pages, 819 KiB

Open AccessReview

Interactions between Gender and Sepsis—Implications for the Future

by Ines Lakbar, Sharon Einav, Nathalie Lalevée, Ignacio Martin-Loeches, Bruno Pastene and Marc Leone

Microorganisms 2023, 11(3), 746; https://doi.org/10.3390/microorganisms11030746 - 14 Mar 2023

Cited by 12 | Viewed by 5534

Abstract

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is [...] Read more.

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen–cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock. Full article

(This article belongs to the Special Issue Sepsis and Septic Shock)

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