The LAUsanne STAPHylococcus aureus ENdocarditis (LAUSTAPHEN) score: A prediction score to estimate initial risk for infective endocarditis in patients with S. aureus bacteremia

IntroductionInfective endocarditis (IE) is a common complication of Staphylococcus aureus bacteremia (SAB). The study aimed to develop and validate a prediction score to determine IE risk among SAB.MethodsThis retrospective study included adults with SAB (2015–2021) and divided them into derivation and validation cohorts. Using the modified 2015 European Society of Cardiology modified Duke Criteria for definite IE, the LAUSTAPHEN score was compared to previous scores.ResultsAmong 821 SAB episodes, 419 and 402 were divided into derivation and validation cohorts, respectively. Transthoracic and transoesophageal echocardiography (TOE) were performed in 77.5 and 42.1% of episodes, respectively. Definite IE was diagnosed in 118 episodes (14.4%). Derivation cohort established that cardiac predisposing factors, such as cardiac implantable electronic devices, prolonged bacteremia ≥48 h, and vascular phenomena were independently associated with IE. In addition to those parameters, native bone and joint infections were used to constitute the LAUSTAPHEN score. LAUSTAPHEN and VIRSTA scores misclassified <4% of IE cases as low risk. Misclassification using POSITIVE and PREDICT scores was >10%. The number of TOEs required to safely exclude IE were 66.9 and 51.6% with VIRSTA and LAUSTAPHEN, respectively.DiscussionLAUSTAPHEN and VIRSTA scores exhibited the lowest misclassification rate of IE cases to the low-risk group. However, the number of patients requiring TOE was higher for VIRSTA than for LAUSTAPHEN

Treatment and Outcomes of Clostridioides difficile Infection in Switzerland: A Two-Center Retrospective Cohort Study

Objectives: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, often complicated by severe infection and recurrence with increased morbidity and mortality. Data from large cohorts in Switzerland are scarce. We aimed to describe diagnostic assays, treatment, outcomes, and risk factors for CDI in a large cohort of patients in Switzerland. Methods: We conducted a retrospective cohort study of CDI episodes diagnosed in patients from two tertiary care hospitals in Switzerland. During a 3-month follow-up, we used a composite outcome combining clinical cure at day 10, recurrence at week 8, or death, to evaluate a patient's response. Unfavorable outcomes consisted in the occurrence of any of these events. Results: From January 2014 to December 2018, we included 826 hospitalized patients with documented CDI. Overall, 299 patients (36.2%) had a severe infection. Metronidazole was used in 566 patients (83.7%), compared to 82 patients (12.1%) treated with vancomycin and 28 patients (4.1%) treated with fidaxomicin. Overall mortality at week 8 was at 15.3% (112/733). Eighty-six patients (12.7%) presented with clinical failure at day 10, and 78 (14.9%) presented with recurrence within 8 weeks; 269 (39.8%) met the composite outcome of death, clinical failure, or recurrence. The Charlson Comorbidity Index score (p < 0.001), leukocytes > 15 G/L (p = 0.008), and the use of metronidazole (p = 0.012) or vancomycin (p = 0.049) were factors associated with the composite outcome. Conclusions: Our study provides valuable insights on CDI treatment and outcomes in Switzerland, highlights the heterogeneity in practices among centers, and underlines the need for the active monitoring of clinical practices and their impact on clinical outcomes through large multicentric cohorts. Keywords: Clostridioides difficile; mortality; outcomes; predictive factors; recurrence; severe infection; treatment

Methicillin-Resistant Staphylococcus aureus ST80 Induce Lower Cytokine Production by Monocytes as Compared to Other Sequence Types

Methicillin-resistant Staphylococcus aureus (MRSA) remains an important cause of nosocomial and community-associated infections due to its ability to produce toxins and evade host’s immune responses. The aim of the present study was to investigate the association of monocytes immune response in terms of cytokines produced after inoculation with different MRSA clones. Thirty-one clinical MRSA strains were selected on the basis of clonal types, accessory gene regulator (agr) groups and toxin genes carriage. Isolates were identified as S. aureus by Gram stain, catalase, coagulase production and PCR for nuc gene. The presence of mecA, lukS/lukF-PV (Panton-Valentine Leukocidin) and tst (Toxic Shock Syndrome Toxin-1) genes, as well as, the determination of agr groups was performed by PCR. Clonality was investigated by means of multi-locus sequence typing (MLST). Peripheral blood mononuclear cells were stimulated with live bacterial cells for 45 min at a ratio of 1:10. Cells were incubated for 10 h and supernatants were collected. The levels of Tumor Necrosis Factor alpha (TNFa), IL-1b, IL-8, IL-6, IL-12p40, IL-10, interferon-gamma (IFN-γ) and IL-2, were measured by Human Cytokine Multiplex Immunoassay kit. Thirteen strains were tst and 12 lukS/lukF-PV-positive. Seven strains belonged to ST80 and ST225, five to ST30 and ST239, while the remaining seven isolates were grouped together as “other.” Strains belonging to ST80 induced statistically lower levels of TNFa, IL-1b, IL-8, IL-6, IL-10, IFN-γ, and IL-2. PVL-positive strains classified into ST80 clone induced statistically lower concentrations of most cytokines as compared to PVL-positive strains belonging to other clones, tst-positive strains and toxin-negative ones. Strains of agr3 group belonging to ST80 induced statistically lower concentrations of most tested cytokines as compared to agr3 strains not-belonging to ST80, agr2 or agr1. This low induction of immune response by MRSA ST80 cannot be attributed to the presence of neither lukS/lukF-PV nor agr3

Evaluation of the 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria for the diagnosis of infective endocarditis in a multicenter cohort of patients with Staphylococcus aureus bacteremia

BACKGROUND The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB). METHODS This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018-23) or IE expert clinicians (2014-17). RESULTS Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% versus 7%, P 0.026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% versus 5%, P 0.461). CONCLUSIONS The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria, show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis

Background Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). Methods This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. Results In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). Conclusions The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria

Early KPC-Producing Klebsiella pneumoniae Bacteremia among Intensive Care Unit Patients Non-Colonized upon Admission

Among 140 patients colonized by KPC-producing Klebsiella pneumoniae (KPC-Kp) between fourth and seventh day of Intensive Care Unit stay, 24 developed bacteraemia immediately after colonization. Colistin-resistance of the colonizing isolate was the factor significantly associated with early KPC-Kp bacteraemia (P < 0.001; OR 6.6, 95% CI 2.4–18.4), a worrisome finding since infections by colistin-resistant isolates is associated with increased mortality due to limited remaining therapeutic options

Predicting Venous Thromboembolic Events in Patients with Coronavirus Disease 2019 Requiring Hospitalization: an Observational Retrospective Study by the COVIDIC Initiative in a Swiss University Hospital.

Coronavirus disease 2019 (COVID-19) can result in profound changes in blood coagulation. The aim of the study was to determine the incidence and predictors of venous thromboembolic events (VTE) among patients with COVID-19 requiring hospital admission. Subjects and Methods. We performed a retrospective study at the Lausanne University Hospital with patients admitted because of COVID-19 from February 28 to April 30, 2020. Among 443 patients with COVID-19, VTE was diagnosed in 41 patients (9.3%; 27 pulmonary embolisms, 12 deep vein thrombosis, one pulmonary embolism and deep vein thrombosis, one portal vein thrombosis). VTE was diagnosed already upon admission in 14 (34.1%) patients and 27 (65.9%) during hospital stay (18 in ICU and nine in wards outside the ICU). Multivariate analysis revealed D-dimer value > 3,120 ng/ml (P < 0.001; OR 15.8, 95% CI 4.7-52.9) and duration of 8 days or more from COVID-19 symptoms onset to presentation (P 0.020; OR 4.8, 95% CI 1.3-18.3) to be independently associated with VTE upon admission. D-dimer value ≥ 3,000 ng/l combined with a Wells score for PE ≥ 2 was highly specific (sensitivity 57.1%, specificity 91.6%) in detecting VTE upon admission. Development of VTE during hospitalization was independently associated with D-dimer value > 5,611 ng/ml (P < 0.001; OR 6.3, 95% CI 2.4-16.2) and mechanical ventilation (P < 0.001; OR 5.9, 95% CI 2.3-15.1). VTE seems to be a common COVID-19 complication upon admission and during hospitalization, especially in ICU. The combination of Wells ≥ 2 score and D - dimer ≥ 3,000 ng/l is a good predictor of VTE at admission

Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients.

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19