Abstract Background The utility of follow-up blood cultures (FUBCs) in patients with gram-negative bacteremia (GNB) is unsettled. In practice, the use of FUBCs is variable. Understanding practice variation and drivers of FUBCs ordering may clarify how clinicians identify patients at high risk for persistent GNB. Methods We conducted a global survey (2/21/2024–4/9/2024) of healthcare workers using 10 hypothetical clinical scenarios to assess FUBC decision-making in GNB. Scenarios varied clinical factors and risk of persistence using the published AIMS scoring tool (Antibiotics, Infection source, Medical conditions, Serratia). The anonymous web-based survey was distributed via listservs, email, and social media. Inter-respondent agreement was assessed using Fleiss’ kappa (κ). Mixed-effect logistic regression identified factors associated with FUBC recommendations. Results Among 864 clinicians from 50 countries, 691 (80%) provided recommendations across 10 scenarios (6,910 recommendations). Most were physicians (86.5%) and infectious disease specialists (79.7%). FUBCs were frequently recommended, with >50% of clinicians endorsing FUBCs in 6 of 10 scenarios. Overall agreement was fair (κ=0.26; 95% CI, 0.10–0.43). In adjusted analyses, factors associated with FUBC recommendations included female respondent sex (aOR 1.40; p=0.042), higher AIMS score (aOR 1.78 per point; p<0.0001), older patient age (aOR 2.90; p<0.0001), inadequate source control (aOR 4.77; p<0.0001), and clinical instability (aOR 114.99; p<0.0001). Conclusions In this survey study, clinicians frequently recommended FUBCs, particularly in clinical vignettes with higher AIMS scores, inadequate source control, and clinical instability. Only fair agreement across risk-stratified scenarios suggests substantial practice variation and supports the need for prospective studies to understand when and in whom FUBCs should be used.

OBJECTIVES:The DENOVA score was developed to support risk stratification for infective endocarditis (IE) in patients with Enterococcus faecalis bacteremia (EfB) and to guide echocardiographic evaluation; external validation remains, however, limited. The objective of this study was to externally validate the DENOVA score in a large prospective international cohort of patients with EfB. METHODS:Prospective multicentre cohort study (2019-2024) conducted across 23 centres in six countries (Italy, Spain, Israel, Brazil, Switzerland, and Romania), including adult patients with monomicrobial EfB who underwent at least one echocardiographic evaluation as part of the study protocol. Definite IE was defined according to the 2023 Duke criteria. The DENOVA score was externally validated; discrimination was assessed by the area under the receiver operating characteristic curve, calibration by observed versus predicted risk plots, and clinical utility by decision curve analysis at the predefined threshold (DENOVA ≥3). Performance of the NOVA score was evaluated as a secondary analysis. RESULTS:Among 543 patients, 125 (23.0%) were diagnosed with IE. When evaluated as a continuous variable, the DENOVA score showed an area under the receiver operating characteristic curve of 0.871 (95% CI 0.835-0.906). At the predefined threshold (DENOVA ≥3), sensitivity was 79.2% (95% CI 71.0-85.9) and specificity was 83.0% (95% CI 79.1-86.5). Decision curve analysis showed that DENOVA ≥3 was associated with positive net clinical benefit across most threshold probabilities, with a reduction in unnecessary transoesophageal echocardiographies. CONCLUSIONS:The study demonstrated that DENOVA supports risk stratification for IE in patients with EfB, informing clinical decision-making and use of transoesophageal echocardiography.

OBJECTIVES:Optimal treatment for Enterococcus faecalis bloodstream infection (EF-BSI) remains a topic of debate. We aim to evaluate the effectiveness of combination therapy compared with monotherapy in patients with EF-BSI and no endocarditis. METHODS:This was a target trial emulation based on a prospective, multicentre, international dataset collected in 24 international centres from January 2019 to December 2024. We included all adult patients with monomicrobial EF-BSI with negative echocardiography within 7 days from BSI onset. Exclusion criteria were diagnosis of endocarditis, not receiving or completed the therapy at randomization. Primary endpoint was clinical failure defined as a composite of death, relapse of EF-BSI, and diagnosis of endocarditis, at 90 days. RESULTS:Overall, 373 patients were eligible for inclusion, 267 of whom (71%) received monotherapy, mainly ampicillin (174 of 267, 65%); most prescribed combination regimens were ampicillin with either ceftriaxone or gentamicin (80 of 106, 75%). The composite clinical failure was met by 114 of 373 (31%) patients. The outcomes among patients who received monotherapy or combination treatment were 75 of 267 (28%) versus 39 of 106 (36%); p 0.185, leading to an overall risk difference in favour of monotherapy of 2% (95% CI, -10% to 15%). Sepsis or septic shock at the time of presentation was the only independent variables associated with clinical failure, after performing a weighted univariable and multivariable Cox regression model (adjusted hazard ratio, 0.85; 95% CI, 0.52-1.39). CONCLUSIONS:With the limitation of our sample size and observational design, we were not able to observe a better outcome associated with combination treatment for EF-BSI. If confirmed, these results would promote therapeutic simplification according to antimicrobial stewardship principles.

A highly sensitive and specific liquid chromatography-tandem mass spectrometry method was developed, fully validated, and successfully implemented for routine analysis to simultaneously quantify Bictegravir, Emtricitabine, Doravirine, Cabotegravir, Lenacapavir, Fostemsavir, Tenofovir alafenamide, and their metabolites, Temsavir and Tenofovir, in human plasma. The sample preparation employed a commercial liquid-liquid extraction kit optimized for low plasma volumes (50 μL), which also included the Internal Standard. The method demonstrated excellent precision, accuracy, and robustness, making it suitable for pharmacokinetic and therapeutic drug monitoring applications. Analyte separation was carried out using a gradient elution program over a total run time of seven minutes, with a flow rate of 0.35 mL/min. The mobile phase consisted of solvent A (water containing 0.1 % formic acid) and solvent B (acetonitrile containing 0.1 % formic acid). Detection was performed using a QTRAP® 5500 triple quadrupole mass spectrometer (SCIEX) equipped with an electrospray ionization source operating in positive ion mode. Ion monitoring was performed in multiple reaction monitoring (MRM) mode for all analytes. The method was validated in accordance with European Medicines Agency (EMA) guidelines across clinically relevant concentration ranges. The proposed method was successfully implemented in routine analysis. Following the initial months of application, biological samples from 165 patients were analyzed primarily to assess therapy adherence and confirm that drug blood concentrations reached the minimum threshold. Additionally, data on drug pharmacokinetics were obtained. Our findings indicate that the proposed method is a reliable and accurate tool for high-throughput screening that could be readily used by the clinicians to optimize therapeutic treatments, verify patients' adherence and reduce drug-related toxicities.

Ventilator-associated bacterial pneumonia (VABP) is a common infection in critically ill patients in intensive care units (ICU), with attributable mortality of up to 13

Abstract Background Previously considered a rare opportunistic pathogen, Serratia is now an emerging cause of bacteremia. However, the demographics and outcomes of patients with Serratia bacteremia remain poorly understood. We thus compared the risk factors and outcomes of patients with Serratia bacteremia relative to other Enterobacterales species in a prospectively ascertained cohort of hospitalized patients. Rates of device infection in patients with medical devices. Rates of device infection in patients with medical devices stratified by device type. P values ≤0.05 are considered statistically significant and indicated (*). Methods Patients with gram-negative bacteremia (GNB) were prospectively enrolled from 2002-2021 at Duke University. Clinical characteristics and outcomes were compared among patients with bacteremia due to Serratia and other Enterobacterales. Multivariable logistic regression models were used to determine features independently associated with outcomes. Risk factors associated with device-associated infection. Risk factors associated with device-associated infection. The multivariable models of factors associated with underlying device infection in patients with any medical device (A) and only cardiac devices (B) and gram-negative bacteremia are shown. P values ≤0.05 are considered statistically significant and indicated (*). Results Among 2676 patients with GNB, 173 (6.5%) had Serratia bacteremia. Patients with Serratia bacteremia, relative to GNB caused by other Enterobacterales, were more likely to have a medical device (59% vs 35.6%; P< 0.001), device-associated infection (42.2% vs. 21.3%, P< 0.001), and persistent bacteremia (23.2% vs. 12.9%; P< 0.001). Among all patients with a medical device (n = 993; 37.1%), Serratia was associated with an increased risk of any device infection in an adjusted model (odds ratio (OR) 2.031; 95% confidence interval (CI), 1.234-3.343). The risk for device infection was highest among patients with cardiac devices (OR 3.947, 95% CI 1.449-10.751). Conclusion Compared to patients with GNB due to other Enterobacterales, patients with Serratia bacteremia were more likely to have a device infection in general, a cardiac device-associated infection in particular, and persistent bacteremia. Disclosures Antonella Castagna, MD, Bristol-Myers Squibb: Advisor/Consultant|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck Sharp & Dohme: Advisor/Consultant|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) Joshua T. Thaden, MD, PhD, National Institutes of Health K08 AI171183 (Thaden): Grant/Research Support Stacey Maskarinec, MD, PHD, National Institutes of Health K23 HL159275 (Maskarinec): Grant/Research Support

A hub and spoke model for optimizing long-term treatment of chronic staphylococcal infections with dalbavancin based on therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) was implemented. This multicentric retrospective cohort study included patients receiving dalbavancin monotherapy lasting >6 weeks at different spoke hospitals having treatment optimized by means of a TDM-guided ECPA program at a hub hospital. Optimal pharmacokinetic/pharmacodynamic target against staphylococci with an MIC up to 0.125 mg/L was defined as dalbavancin concentrations >8.04 mg/L. Patients received dalbavancin therapy for curative (curative group) or suppressive (suppressive group) purposes. Clinical outcome was assessed by means of repeated ambulatory visits. A total of 12 spoke hospitals applied for 414 TDM-based ECPA for 101 patients, of whom 64.4% (65/101) were treated for curative and 35.6% (36/101) were for suppressive purposes. In the curative and suppressive groups, TDM-based ECPA optimized treatment for up to 14 and 28 months, respectively, and ensured median optimal exposure of 95.7% and 100%, respectively. In the curative group, having <70% of treatment time with concentrations above the optimal target increased failure risk [odds ratio (OR), 6.71; confidence interval (CI), 0.97-43.3; P = 0.05]. In the suppressive group, infective endocarditis was associated with an increased risk of ineffective treatment (OR, 8.65; CI, 1.29-57.62; P = 0.046). Mild adverse events were reported in 4.5% (5/101) of cases. A hub and spoke TDM-guided ECPA program of dalbavancin may be cost-effective for optimizing long-term treatment of chronic staphylococcal infections and for patients admitted to hospitals lacking in-house MD clinical pharmacologists.

Background/Objectives: Non-HACEK Gram-Negative Infective Endocarditis (NHGNIE) is a rare but increasingly recognized condition associated with high morbidity and mortality. Its incidence is rising among people who inject drugs (PWID), patients with prosthetic valves or cardiac devices, and those with significant healthcare exposure. We aimed to provide a comprehensive review of the epidemiology, pathogenesis, diagnosis, clinical features, and management of NHGNIE. Methods: We conducted a narrative synthesis of published cohort studies, case series, guideline documents, and recent registry data addressing NHGNIE. Evidence was extracted and critically appraised with emphasis on epidemiological patterns, microbial etiology, diagnostic frameworks, therapeutic strategies, and outcomes. Special focus was given to pathogen-specific differences and the impact of antimicrobial resistance. Results: NHGNIE accounts for approximately 1.5–10.7% of IE cases worldwide, with marked geographical variability. Pseudomonas aeruginosa, Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli are the predominant pathogens, with clinical profiles differing between younger, PWID-based populations and older, comorbidity-affected cohorts. Advances in molecular diagnostics and imaging have improved case identification, though pathogen-specific diagnostic performance remains limited. Outcomes are poor, with in-hospital mortality up to 41%. Antimicrobial therapy is complicated by biofilm formation and potential for multidrug resistance; evidence for combination therapy versus monotherapy is conflicting. Surgical intervention appears to improve outcomes when performed according to guideline-based indications, but results are heterogeneous across studies. Conclusions: NHGNIE is a clinically significant form of IE with complex epidemiology, diagnostic challenges, and limited evidence to guide treatment. Effective management requires individualized care coordinated within a multidisciplinary “endocarditis team”.

The incidence of vertebral osteomyelitis is increasing with heterogeneity in clinical presentation and outcome. Lack of pathogen identification could complicate clinical management. This study aimed to compare the clinical characteristics, management and outcome of patients with vertebral osteomyelitis (VOs) with known aetiology (KAe) and unknown aetiology (UAe). A total of 92 patients with VOs were included, 57 (62%) with KAe and 35 (38%) with UAe. In our cohort, VO with known etiology was more commonly related to a worse clinical presentation, more frequent hospitalization, required more therapeutic lines, and experienced delays in switching to oral therapy.

Objectives: Previously considered a rare opportunistic pathogen, Serratia is now an emerging cause of bacteraemia. We compared the risk factors and outcomes of patients with Serratia bacteraemia relative to other Enterobacterales in a cohort of hospitalized patients. Methods: Patients were prospectively enrolled from 2002 to 2021 at Duke University. Characteristics and outcomes were compared among patients with bacteraemia due to Serratia and other Enterobacterales. Regression models were used to determine features associated with outcomes. Whole-genome sequencing was performed to characterize the phylogenetic diversity of Serratia isolates associated with device infections. Results: Of 2676 patients, 173 (6.5%) had Serratia bacteraemia. Among patients with a medical device (n = 993; 37.1%), Serratia was associated with an increased risk of device infection in an adjusted model (adjusted OR [aOR], 2.03; 95% CI, 1.23–3.34). Device infection risk was highest among patients with cardiac devices (OR, 3.95; 95% CI, 1.45–10.75). Serratia was associated with a greater risk of persistent bacteraemia (aOR, 1.66; 95% CI, 1.08–2.54). Whole-genome sequencing of Serratia isolates (n = 93) revealed considerable genetic diversity, with no association between phylogenetic clusters and device infections overall (P = 0.35) or cardiac device infections specifically (P = 0.13). Conclusions: Compared with other Enterobacterales, patients with Serratia bacteraemia were more likely to have a device infection in general, a cardiac device-associated infection in particular, and persistent bacteraemia. Whole-genome sequencing demonstrated genomic diversity of Serratia marcescens isolates, suggesting that the molecular basis for device infection is not clonal. Further studies are needed to elucidate the mechanism underpinning this finding.

The global rise in infections due to multidrug-resistant Gram-negative bacteria (MDRGNB) infections has disproportionately impacted immunocompromised (IC) hosts. Cefiderocol, a novel siderophore cephalosporin, exhibits potent activity against MDRGNB, but limited data exist on its use in IC patients. This study aimed to describe cefiderocol use in IC patients. Patients and therapy characteristics were descriptively reported, and outcomes were compared between IC and non-IC patients. Cox regression models were used to identify factors associated with mortality. Among 185 patients, 84 (45.4

Abstract Background Studies examining the impact of follow-up blood cultures (FUBCs) in patients with gram-negative bacteremia (GNB) have shown mixed results. In practice, FUBCs are variably obtained. Understanding practice variation and motivation for ordering FUBCs is important to determine how providers stratify patients at high risk for persistent GNB.Figure 1:Global distribution of survey respondents (n=864). Methods We surveyed clinicians (physicians, pharmacists, clinical microbiologists, physician assistants, nurses, medical trainees) globally between 2/21/24-4/9/2024 to understand when they would obtain FUBCs in patients with GNB using 10 hypothetical patient scenarios. Scenarios were generated by varying age, clinical status after 48 h of antibiotics, and risk of persistent GNB based on our published AIMS scoring tool (Antibiotics, Infection source, Medical conditions, Serratia). The survey contained 4 low-risk cases (AIMS 0-1), 3 intermediate-risk cases (AIMS 2-3), and 3 high-risk cases (AIMS 4-6). This anonymous web-based survey was distributed through listservs, email, and social media.Table 1:Demographic characteristics of survey respondents (n=864). Results In total, 864 respondents from 50 different countries and 6 continents (Figure 1) opened the survey and provided 791 recommendations on FUBC ordering (791/864; 91.5%). Respondent demographics are described in Table 1. Most respondents were physicians (86.5%) specializing in infectious diseases (79.7%) who were within 10 years of training completion (52.3%); a plurality managed least 6-10 cases of GNB/month (22.7%). FUBCs were frequently recommended, with >40% of respondents recommending FUBCs in 7/10 scenarios. Fair inter-respondent agreement was seen across all scenarios (Fleiss kappa 0.27), with notable agreement for cases with high AIMS scores (Fleiss kappa 0.24) (Figure 2). Patient age and clinical status after antibiotic administration were not associated with FUBC recommendations. Survey results of FUBC recommendations by individual case scenario (1-10) stratified by low, intermediate, and high risk AIMS scores. Bar graphs represent percentage of recommendations in favor (yes) or not in favor (No) of FUBCs in patients with GNB. Conclusion In this survey study, clinicians risk stratified hypothetical patients with GNB when assessing the need for FUBC. There was fair agreement among clinicians that high risk patients should get FUBCs. Future studies should focus on variables which prompt FUBC ordering in low-risk patients, an area of disagreement among responders, and ideally in the form of randomized clinical trial. Disclosures Joshua T. Thaden, MD, PhD, National Institutes of Health K08 AI171183 (Thaden): Grant/Research Support Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) Sonali Advani, MBBS, MPH, FIDSA, Biomerieux: Advisor/Consultant|GSK: Advisor/Consultant|Locus Biosciences: Advisor/Consultant|Sysmex America: Advisor/Consultant Stacey Maskarinec, MD, PHD, National Institutes of Health K23 HL159275 (Maskarinec): Grant/Research Support

To evaluate the value of a computed tomography (CT) protocol, including ECG-gated cardiac angiographic and venous phase, in patients with infective endocarditis (IE). From January 2019 to October 2022, consecutive patients with IE submitted to total-body CT, including ECG-gated cardiac acquisition in angiographic and venous phase, were enrolled. Transesophageal echocardiography was performed in all cases. Rate of local complications including vegetation, pseudoaneurysm, abscess, fistula and valve dehiscence was compared in CT and echocardiography. Systemic embolization was identified through CT scans. Seventy-six adults (median age 69 [IQR 55–77] years old; males 54/76, 71

Abstract Background Aim of this study is to evaluate factors associated with uptake of pneumococcal vaccination after invasive pneumococcal disease (IPD). Since pneumococcal infection doesn’t protect from future ones, vaccination is recommended in patients who recover from IPD. Table 1 Population's characteristics. Methods Retrospective, bicenter cohort study of patients hospitalized with invasive pneumococcal disease at IRCCS San Raffaele Hospital (Milan, Italy) and ASST Manzoni Hospital (Lecco, Italy) between January 1st 2015 and December 31st 2019. Patients older than 18 years with positive blood or cerebrospinal fluid cultures for Streptococcus pneumoniae were included. Patients who died before discharge and whose vaccinal record and discharge documentations were not available were excluded. All vaccination data were retrieved through Italian national vaccination portal (SIAVR). Follow-up data were updated until March 31st, 2024. The characteristics of patients who were vaccinated (VAX) and were not vaccinated (UNVAX) after the event were compared using the chi-square test for categorical variables and the Mann-Whitney U-test for continuous variables. Table 2 Characteristics of vaccination cycles. Results The characteristics of the 211 included patients are described in table 1, completed vaccination cycles in table 2. Only 26 patients (12.3%) received an indication at discharge to get vaccinated for S. pneumoniae, and 47 (22.2%) patients were vaccinated during the observation period, after a median of 6.6 (2.3-29.9) months after the event. There was no difference in age between the two groups (70.7 [60.1-78.4] vs 69.5 [58.8-78.5], p-value=0.82), while a greater proportion of VAX patients was male (33 [70.2%] vs 86 [52.4%], p-value=0.03). Charlson comorbidity index was similar between the two groups (5 [3-6] vs 5 [3-6], p-value=0.845), but a significant higher percentage of VAX patients had lymphoma (8 [17%] vs 8 [4.9%], p-value=0.006). Patients who received an indication to vaccinate were significantly more likely to receive pneumococcal vaccination (16 [34%] vs 10 [6.1%], p-value< 0.001). Conclusion Our cohort revealed low pneumococcal vaccination uptake, with inadequate frequency of vaccination indication at discharge. Reinforcing prevention culture among patients and physicians is imperative. Disclosures Antonella Castagna, MD, Bristol-Myers Squibb: Advisor/Consultant|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck Sharp & Dohme: Advisor/Consultant|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria

Objective:Bloodstream infections (BSIs) significantly impact morbidity and mortality. Despite emerging evidence supporting optimal management, substantial variability persists among non-infectious disease (ID) physicians. This study assessed non-ID physicians' knowledge and attitudes in BSI management, identifying critical gaps to inform antimicrobial stewardship (AMS) interventions. Methods:In December 2024, we conducted an online questionnaire among non-ID physicians at the Provincial Health Care Agency, Trento, Italy. An 18-item questionnaire, developed by a multidisciplinary group, evaluated key domains of BSI management, including diagnostic strategies, antibiotic selection, treatment duration, follow-up management, and ID consultation practices. Descriptive statistics were used to analyse response patterns. Results:Of 128 respondents, 99% expressed willingness to follow internal BSI guidelines, and 94% supported multidisciplinary feedback. Overall, 50.8% correctly identified the optimal 14-day antibiotic duration for uncomplicated Staphylococcus aureus bacteraemia (SAB), and 67.2% selected appropriate treatment for MSSA infections. The prevalence of complicated SAB was underestimated by 51.6% of participants. Follow-up blood cultures and echocardiography were variably recommended (40.6% and 71.9%, respectively, for SAB). 50.8% correctly indicated a 7-day therapy for uncomplicated Gram-negative BSIs, and 49.2% appropriately chose first-line treatments for susceptible Enterobacterales. Familiarity with antibiotic de-escalation (86.7%) and IV-to-oral therapy (94.5%) was high, but appropriate application knowledge was inconsistent. Penicillin safety in reported low-risk allergies was recognized by 63.3%, and carbapenems as alternatives by 46.1%. Conclusions:These findings highlights substantial knowledge gaps among non-ID physicians regarding bacterial BSI management. These findings support targeted AMS interventions under the Bacteraemia Evidence-based Active Treatment (BEAT) initiative to improve clinical outcomes.

INTRODUCTION:Infectious diseases are a major global health concern, responsible for significant morbidity and mortality. To advance the understanding and treatment of these diseases, biobanks and biorepositories play a crucial role in guaranteeing sample traceability through their entire life cycle (collection, acquisition and registration, processing, storage, distribution) and future analysis of clinical and biological data. METHODS AND ANALYSIS:The INfectious DIsease REgistry BIObank (INDI-REBIO) is an observational, prospective, monocentric, open-ended registry with ad hoc procedures and a systematic collection of uniform clinical, laboratory, imaging and therapeutic data of patients with suspected or microbiologically documented bacterial, viral, fungal and parasitic infectious diseases from the IRCCS San Raffaele Hospital (Milan, Italy). The study aims to collect both uniform data and biological samples such as blood and other relevant specimens. The registry aims to include significant patient numbers across various conditions (among others: bloodstream infections, endovascular infections as infective endocarditis, central nervous system infections, bone and joint infections, multidrug-resistant organisms (MDROs) colonisation, sexually transmitted infections, HIV infection, emerging and re-emerging infectious diseases), enabling comprehensive research on disease evolution, treatment outcomes and the identification of biomarkers. ETHICS AND DISSEMINATION:The study adheres to ethical principles outlined by the Helsinki Declaration and Good Clinical Practice guidelines. It has received ethical approval (Comitato Etico CET Lombardia 1, CET 138-2023) and is registered on clinicaltrials.gov (NCT06418048). Participants will provide informed consent and can withdraw at any time. The study results will be disseminated through major international conferences and submitted to peer-reviewed research journals. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov, NCT06418048.

Incidence of breakthrough proven-probable invasive fungal infections (b-PP-IFIs) in allogeneic haematopoietic cell transplant recipients (allo-HCT-r) receiving mould-active prophylaxis (MAP) and post-transplant cyclophosphamide (PT-Cy) is largely unknown. Retrospective study on allo-HCT-r, classified at high-risk for IFIs whether ≥1 of the following conditions was met: 1] active disease; 2] cord-blood; 3] previous transplant; 4] acute graft-versus-host-disease (a-GVHD) grade≥3; 5] mismatched-related or unrelated donor with neutropenia before transplant or grade-2 a-GVHD or Cytomegalovirus infection. Objectives were to estimate cumulative incidence function (CIF) of b-PP-IFIs, evaluate infection-related mortality (IRM) and predictive factors of b-PP-IFIs. Overall, 473 allo-HCT-r (n = 286 posaconazole, n = 187 voriconazole) were analysed: 64.7

SCOPE:Vascular graft or endograft infection (VGEI) is a severe complication requiring a multidisciplinary approach combining surgery and antimicrobial therapy. This study aimed to develop expert consensus on the management and follow-up of VGEI, with a focus on antimicrobial strategies. METHODS:A modified Delphi method was conducted to reach consensus on key aspects of VGEI care, including antimicrobial treatment, surgical management, and follow-up. An expert panel representing infectious diseases, vascular and cardiothoracic surgery, microbiology, and nuclear medicine participated in four rounds of surveys. Ten general and 35 specific statements were rated using a five-point Likert scale. Statements with ≥75% agreement (agree/strongly agree) were considered to have achieved consensus. Internal consistency across rounds was assessed using Cronbach's alpha (>0.80). QUESTIONS ADDRESSED BY THE DELPHI METHOD AND RECOMMENDATIONS:The panel agreed that empirical antimicrobial therapy should be initiated only in patients with complications (e.g. sepsis and bleeding) or when diagnostic intervention is delayed. Empirical therapy must be individualized based on graft location and risk factors. For abdominal VGEI without aorto-enteric fistula and unknown pathogens, initial coverage should target gram-positive cocci, gram-negative bacilli, and anaerobes, with consideration for Methicillin-Resistant Staphylococcus aureus (MRSA)/Methicillin-Resistant Staphylococcus epidermidis (MRSE) based on risk. For thoracic VGEI without fistula, gram-positive coverage is prioritized, with optional MRSA coverage. Postoperative treatment duration should be individualized. In cases of complete graft removal and replacement with autologous veins, a 6-week antibiotic course is recommended, with early oral switch if bioavailable options are available. If prosthetic material remains, at least 4 to 6 weeks of intravenous therapy followed by oral treatment for a total of 12 weeks is advised. Prolonged therapy should be considered in cases with virulent pathogens, incomplete source control, or persistent inflammatory markers. The study provides practical, expert-based antimicrobial guidance for VGEI management and emphasizes the importance of individualized, microbiologically informed therapy within a multidisciplinary care framework.

Introduction: Infective endocarditis (IE) is a life-threatening condition and a rare cause of ischemic stroke (IS). This study aimed to evaluate the utility of analyzing cerebral thrombi, obtained through endovascular thrombectomy in IS, for the pathological diagnosis of IE. Patients and methods: Cerebral thrombi from three groups of IS patients were compared: definite IE ( n = 10), cardioembolic stroke without and with concomitant infection (CE-I − : n = 30, CE-I + : n = 10). We performed histological examination, molecular biology, and microbiological tests on cerebral thrombi, to detect microorganisms and assess their composition. Results: Median age of included patients was 73 years and 50% were females. Hematoxylin & Eosin and Grocott-Gomori Methenamine Silver stains detected microorganisms in all IE cerebral thrombi, and none in the control groups. Thrombus PCR detected relevant microorganism in n = 2/7 IE. Compared to control groups, IE thrombi were characterized by significant lower content of red blood cells (median [IQR]: IE = 7.4 [4.2–26.7], CE-I − = 49.3 [17–62.6], CE-I + = 57.5 [40.7–60.8], % over thrombus section area [%TSA], p = 0.001), increased von Willebrand Factor (IE = 23.9 [19.1–32], CE-I − = 11.2 [8.2–12.8], CE-I + = 12.9 [10.7–18.3], %TSA, p = 0.001), cell-dominant pattern of Neutrophil Extracellular Traps (IE = 100%, CE-I − = 69%, CE-I + = 70%, p ⩽ 0.001), and more frequent sub-acute or chronic thrombus age classification ( p ⩽ 0.001). These latter thrombus features displayed good discriminative ability between IE and controls, with AUC values between 0.84 and 0.95. Discussion: Multimodal analysis of cerebral thrombi in IS with suspected IE supports early and definite pathological diagnosis by detecting pathogens and assessing changes in thrombus composition.

BACKGROUND:Stenotrophomonas maltophilia is a Gram-negative bacillus that may cause a range of infections, most frequently bloodstream and respiratory infections. S. maltophilia exhibits intrinsic resistance to several antibiotics including carbapenems. Clinical assessment and treatment of a patient with positive S. maltophilia cultures are challenging. OBJECTIVES:We aimed to provide a resource for clinicians to help diagnose and treat S. maltophilia infections. SOURCES:A comprehensive literature search on S. maltophilia infections was conducted using PubMed, with no restrictions on publication date. CONTENT:The review uses a hypothetical clinical vignette as a context to explore the epidemiology, risk factors, clinical presentation, mortality, diagnostic management, antibiotic resistance mechanisms, and antibiotic management of S. maltophilia infections. IMPLICATIONS:The assessment and treatment of S. maltophilia infections remain challenging. Standardized indications to distinguish colonization from infection and to guide the start of targeted therapy are lacking. The optimal treatment approach has similarly not been established in randomized controlled trials.