Regarding air quality, modern hospitals include both ‘protected’ and ‘unprotected’ areas. Although recommendations exist for maintaining good air quality in protected zones, guidance for unprotected areas remains limited. This gap poses a significant risk, particularly for immunocompromised patients, who are more susceptible to acquiring potentially life-threatening healthcare-associated infections (HAIs) transmitted through the air in these settings. The aim of this review was to review existing evidence on indoor air quality in unprotected (IAQ-U) hospital areas and identify current knowledge gaps. Additionally, some proposals for assessing and maintaining optimal indoor air quality (IAQ) in these settings are presented.A narrative review of the literature on IAQ was conducted, covering the period from 2015 to 2025, and selected available recommendations on IAQ in the healthcare setting were examined. The paper is structured in two sections. The first section reviews the existing evidence on IAQ, while the second presents perspectives and proposals. Specifically, the European Society of Clinical Microbiology and Infectious Diseases could co-ordinate a pilot multi-centre study among selected European hospitals to develop guidelines for assessing IAQ-U hospital areas. Implementation of these proposals could reduce the incidence and associated costs of air-transmitted HAIs and strengthen preparedness for future pandemics.

Most evaluations of the burden of pneumonia in hospitalized patients are partial and concern specific subgroups of patients. However, few studies allow for the assessment of the global scope of the problem and the potential for intervention with guidance that could improve its diagnosis and treatment. This descriptive study conducted in a tertiary-care center aimed to determine the prevalence of pneumonia in hospitalized adults, to characterize its origins and etiology, and to evaluate the feasibility of a telematic intervention to advise on its diagnosis and treatment. A prevalence study was performed on the 653 adult inpatients admitted in July 2025. The pneumonia prevalence per 1,000 admitted patients was overall 36.8, community-acquired 24.5, nosocomial non-ventilator-associated 9.2, and nosocomial ventilator-associated 3.1. An etiological agent was identified in 29.2% of cases. In a critical review of the cases, opportunities to optimize either diagnosis or treatment were detected in 100% of pneumonia patients. After 30 days of dynamic follow-up of the selected cohort, overall mortality was 16.7%.

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.

Background:This study was conducted to investigate the diagnostic value of fungal biomarker differentials and T2Candida polymerase chain reaction (PCR) from catheter and peripheral blood samples and to re-evaluate classical conservative methods, such as differential time to positivity of blood cultures (BCs), for the early identification of catheter-related candidemia (CRC) before catheter removal. Methods:This prospective study was conducted (March 2023-April 2025) in 2 tertiary hospitals in Spain and Italy. Adults (aged ≥18 years) with candidemia and a central venous catheter in place at diagnosis were included, provided catheter removal occurred within 48 hours of index BC positivity. CRC was defined in patients with candidemia who showed 1 or 2 of the following criteria in the catheter tip: (1) ≥ 15 CFU/plate (Maki technique) or ≥ 1000 CFU/mL (sonication) and (2) any Candida growth on the catheter tip. Blood samples were collected from peripheral veins and catheter lumens to compare the differentials of 1,3-β-D-glucan (BDG), Candida albicans germ tube antibodies, mannan antigen, antimannan antibody, and T2Candida PCR results. Diagnostic metrics were calculated for each test. Results:Of 179 episodes of candidemia reviewed, 28 (15.6%) met the inclusion criteria (13 in Spain, 15 in Italy). CRC was confirmed in 11 patients (39.3%) using criterion 1 and in 15 patients (53.6%) using criterion 2. BDG differentials (any difference) demonstrated the highest diagnostic accuracy as follows: sensitivity 81.82%, specificity 82.35%, positive predictive value 75.00%, negative predictive value 87.50%, and overall accuracy 82.14% (criterion 1). However, stricter BDG thresholds (≥20 or ≥30 pg/mL) and the application of criterion 2 reduced the sensitivity. Other biomarkers and T2Candida PCR demonstrated low sensitivity (0%-40%) and variable specificity (25%-100%), with overall accuracies of <64%. Differential time to positivity of BCs yielded a sensitivity of 72.73% and a specificity of 52.94%, with limited accuracy. Conclusions:None of the investigated methods achieved sufficient accuracy to diagnose CRC without catheter removal. Despite the limited sample size, this study emphasizes the limitations of current diagnostic approaches and the need for novel tools for reliable noninvasive identification of CRC.

The collection and interpretation of blood cultures in paediatric patients require specific considerations that make simple extrapolation from adult recommendations inappropriate. In recent years, the incidence and aetiology of paediatric bacteraemia have evolved, influenced by vaccination programmes, improved infection prevention strategies, and increasing clinical complexity, particularly in neonatal, oncohaematological, and intensive care settings. Clinical guidelines recommend blood cultures in neonates and infants with fever without a focus in children with sepsis or shock, with immunosuppression, suspected endovascular infection, meningitis, osteoarticular infections, or severe community-acquired pneumonia. Conversely, routine use is discouraged in clearly viral infections and in mild cases in previously healthy children. Available evidence consistently identifies the volume of blood inoculated as the main determinant of diagnostic performance, and this should be adjusted for age and weight. Obtaining one or two appropriately indicated peripheral blood culture sets, together with proper antisepsis, reduces contamination and improves clinical interpretation. Whenever feasible, both aerobic and anaerobic bottles should be included, given their complementary diagnostic yield. There is no robust evidence that paediatric bottles with smaller broth volumes provide substantial advantages over standard bottles when adequate blood volumes are inoculated. Importantly, no evidence demonstrates that the type of bottle or automated system used influences hospital stay, clinical outcomes, or mortality. This article presents an evidence-informed perspective that integrates current literature with expert clinical judgment, derived from more than four decades of experience at a high-complexity tertiary-care hospital.

Background Management of E faecium bloodstream infections (BSIs) remains debated, particularly the clinical impact of vancomycin resistance, the role of follow-up cultures, and optimal therapeutic regimens. This study aimed to reach expert consensus on these unresolved clinical domains and identify priorities for future research. Methods We first conducted a systematic review and meta-analysis in January 20, 204 focusing on four predefined areas: mortality in E faecium BSIs compared with other BSIs, mortality in vancomycin-resistant enterococci (VRE)-BSIs compared with vancomycin-susceptible enterococci-BSIs, management of catheter-related E faecium BSIs, and 4) optimal antibiotic therapy for VRE-BSIs. These results informed a three-round Delphi process involving a panel of experts. An iterative approach was adopted: 16 initial questions developed from the systematic review (6-point Likert scale) were refined across rounds based on expert feedback. Consensus was defined as at least 80% agreement or disagreement. Findings 13 statements were generated across three broader domains. Regarding clinical outcomes and diagnostics, experts agreed that mortality is heavily influenced by comorbidities; thus, therapeutic assessment should rely on clinical trends and inflammatory markers, with follow-up blood cultures used to confirm eradication. Catheter-related BSI should be managed with device removal and short-course (<7 days) antibiotics in selected uncomplicated cases. For therapeutic management, teicoplanin is preferred for vanB VRE-BSI. For vanA VRE-BSI, both linezolid and high-dose daptomycin (>9 mg/kg per day) are effective, reserving daptomycin-based combinations for challenging cases (deep-seated infections and/or high Minimum Inhibitory Concentrations). Finally, future trials evaluating the impact of antimicrobial therapy should use Desirability-of-Outcome-Ranking analysis; the in-vitro potential of oritavancin justifies targeted randomized trials to define its clinical efficacy in VRE-BSI. Interpretation This paper delineates current evidence and expert consensus on management of E faecium BSI while identifying crucial knowledge gaps to guide future clinical research. Funding None.

Genomic epidemiology has improved our understanding of tuberculosis (TB) transmission beyond MIRU-VNTR analyses, but long-term genomic analysis required to identify transmission clusters remains unfeasible in many settings. Our objective is to evaluate an alternative strategy for obtaining a rapid snapshot of TB-transmission in populations without molecular/genomic systematic surveillance, using Madrid as a model. A total of 454 isolates (2019–2021) were analysed through a three-step sequential approach: (i) Preliminary screening of potential clusters, by a 6-loci MIRU panel; (ii) extended MIRU-24 exclusively on the MIRU-6-clusters; and (iii) WGS applied solely on the MIRU-24-clusters. This process progressively excluded orphan cases, reducing WGS to 13% of total isolates and confirming 17 transmission clusters. Genomic data from six clusters were used to identify strain-marker single-nucleotide-polymorphisms (SNPs), enabling the design of a multiplex-PCR assay followed by targeted nanopore sequencing of the amplicons. This approach allowed the rapid exclusion of cluster involvement in new incident and retrospective cases without requiring WGS. Our strategy based on the identification of clusters by a retrospective sequential application of progressively enhanced discriminatory molecular/genomic methods, coupled with targeted sequencing of amplicons harbouring strain-marker SNPs, may contribute to a more rationalised use of resources and facilitate timely updates on TB-transmission, where universal long-term WGS cannot be assured.

BACKGROUND:Candida bloodstream infections (BSI) are a major cause of disease in hospitalized patients, with particularly high morbidity and mortality among older adults. However, the impact of biological sex on clinical presentation and outcomes in this population remains poorly defined. We evaluated sex-based differences in patients aged ≥65 years with Candida BSI. METHODS:We conducted a retrospective multicenter cohort study across three hospitals in Italy and Spain (2018-2022), including all patients aged ≥65 years with Candida BSI. The primary outcome was 30-day all-cause mortality. Cox regression and 1:1 propensity score matching were used to assess the association between biological sex and mortality and to identify independent predictors of outcome. RESULTS:A total of 1132 patients were included (53.4% male; median age 79 years). Men had a higher comorbidity burden and more severe clinical presentation at onset. Overall, 30-day mortality was 46.9%, with no significant difference between sexes (log-rank p = .929). In multivariable analysis, older age, higher Charlson Comorbidity Index, and septic shock were independently associated with mortality, whereas biological sex was not (aHR 1.19, 95% CI 0.95-1.50, p = .136). After propensity score matching, biological sex was not associated with mortality, while adequate source control was protective (aHR 0.62, 95% CI 0.47-0.82, p = .0008). CONCLUSIONS:In older adults with Candida BSI, short-term mortality is driven primarily by disease severity, comorbidity burden, and adequacy of management rather than biological sex. Optimizing timely antifungal therapy and source control appears critical to improving outcomes in this vulnerable population.

BACKGROUNDIn tuberculosis (TB) surveillance, genomics is mainly used to identify TB patient clusters; growing clusters are commonly attributed to ongoing transmission events.AIMThis study's objective was to explore other factors, in addition to ongoing transmission, contributing to cluster expansion.METHODSThe study population included all 1,886 culture-positive TB cases diagnosed within the whole Almería province population, Spain, between January 2003 and June 2024. Cases' Mycobacterium tuberculosis strains were whole genome sequenced enabling detection of clusters (with pairwise distance between strains < 12 single nucleotide polymorphisms (SNPs)). Evolutionary analyses positioned cases within genomic networks based on SNP distribution. This allowed, together with clinical and epidemiological data, to infer why new cases (diagnosed 3.5 years prior) entered clusters.RESULTSCases' mean age was 37.3 years (standard deviation: 16.4); 71.7% (1,352/1,886) were male and 65.2% (1,230/1,886) migrants from 50 countries, with mostly Moroccan (21.6%; 407/1,886), Romanian (10%; 188/1,886), Senegalese (8.3%; 156/1,886) and Malian (5.2%; 98/1,886) nationalities. We detected 106 clusters, comprising 537 cases in total. The 106 new cases occurred within 53 clusters, including 31 growing clusters (identified pre-2021) and 22 recent clusters (that arose in 2021 and after). Ongoing transmission was responsible for cluster expansion in around one-third of growing clusters (9/31), versus two-thirds (15/22) of recent clusters. Genomic network assessments found that newly clustered cases not due to ongoing transmission, were likely driven by reactivation of past exposures, prolonged diagnostic delays or subclinical periods, or a combination of these factors.CONCLUSIONUnderstanding cluster dynamics guides case-specific management and supports TB control.

Background. There is a paucity of data to guide the management of posttransplant secondary antibody deficiency (SAD). We aimed to evaluate the role of IVIG in solid organ recipients with SAD. Methods. A phase 2, randomized, multicenter, open-label study of solid organ recipients with severe infection and SAD defined as serum IgG <600 mg/dL. The study evaluated the efficacy of adding a fixed protocol of IVIG early after detection of SAD to standard of care (SOC) for the prevention of infection occurring on-study and the treatment of infections, versus SOC. We also assessed reconstitution of humoral immunity in a substudy. Forty‐four transplant recipients were randomized in 6 transplant centers in Spain. The IVIG protocol comprised 2 doses of 15 g (interval 7–15 d) followed by 3 doses of 20 g (interval 15–30 d). The primary endpoint was infection occurring on-study defined as a new severe infection after randomization. Results. Forty-two patients were included in the intention-to-treat analysis (IVIG arm, n = 21 versus non-IVIG arm, n = 21). The rate of infection occurring on-study was lower in patients randomized to receive IVIG versus SOC (23.8% versus 66.7%, Fisher exact test, P = 0.012). The median number of infections occurring on-study was lower in the IVIG group. The median total number of new admissions considered to be related to an infection occurring on-study was significantly lower in IVIG-treated patients. A significant increase in specific anti-cytomegalovirus IgG, anti–varicella zoster IgG, anti-Clostridium difficile toxins A and B IgG, and anti-tetanus toxoid IgG and IgG1 was demonstrated in the IVIG arm. Conclusions. In solid organ recipients with severe infection and SAD, IVIG may reduce infection occurring on-study occurrence versus SOC.

BACKGROUND:Infective endocarditis (IE) carries high morbidity and mortality, largely from neurological complications. The clinical significance of chronic antithrombotic therapy remains uncertain. We assessed whether baseline antithrombotic therapy influences intracranial hemorrhage (ICH) and mortality in left-sided IE. METHODS:We analyzed a prospective multicenter cohort (2008-2018) including all patients with definite left-sided IE. Patients were classified at diagnosis as receiving no therapy (NT), antiplatelet therapy (APT), anticoagulation (AC), or combined therapy (CAT). The primary outcome was 30-day ICH; secondary outcomes included ischemic stroke, embolic events, major bleeding, and all-cause mortality. Multivariable logistic and Cox regression models adjusted for confounders. RESULTS:Among 3236 patients, 182 (5.6%) developed ICH, with the highest incidence in CAT (9.5%) and AC (6.8%). Compared with NT, baseline AC was independently associated with a higher frequency of ICH (adjusted risk ratio [aRR] 1.83, 95% CI 1.16-2.91), with the highest risk observed in CAT (aRR 2.45, 95% CI 1.55-3.87). Antiplatelet therapy was not associated with ICH. Ischemic stroke rates were similar across groups. Combined anticoagulation and antiplatelet therapy independently predicted higher 1-year mortality (adjusted hazard ratio [aHR] 1.21, 95% CI 1.02-1.43). Independent factors associated with ICH were Staphylococcus aureus and Candida spp. IE, extracranial embolism, prior cerebrovascular disease, and septic shock. CONCLUSIONS:These findings highlight the value of baseline antithrombotic exposure, together with microbiologic etiology and prior cerebrovascular disease, for early neurologic risk stratification at the time of IE diagnosis, informing neuroimaging decisions and multidisciplinary discussions involving infectious diseases specialists, neurologist, and cardiac surgeons among other specialists.

Objectives Patients with hematological malignancies (HM) are particularly at risk of developing Clostridioides difficile infection (CDI). The 10th European Conference on Infections in Leukemia (ECIL-10) group developed recommendations for managing CDI in patients with HM, preceded by a survey to document current CDI practices. Methods ECIL members completed an online expert survey on epidemiology, severity criteria, and diagnostic and therapeutic approaches to CDI. Rates were reported using the number of responses as the denominator. Results Overall, 49 experts from different centers responded, including both hematologists and infectious disease specialists. The rate of CDI in adults with HM was 5-10% in 46% of centers and in children in 36% of centers. We identified important limitations in CDI severity definitions, with leukocytosis and hypoalbuminemia being the least useful criteria. Therapeutic choices in patients with HM were predominantly vancomycin, with fidaxomicin used less frequently. Metronidazole monotherapy was used despite data showing lower efficacy. For recurrent CDI, fidaxomicin was the preferred drug. For ≥2nd recurrence, 31% of centers used fecal microbiota transplantation. Conclusions The survey identified discrepancies in current practice and highlighted several unmet needs, including better-defined severity criteria, optimization of the use and duration of available agents, and access to intravenous agents for patients unable to take oral therapy.

Tuberculosis (TB) and cancer share overlapping clinical features that may worsen outcomes when coexist. We aimed to characterize TB in cancer patients and identify predictors of TB-related mortality in a low TB-prevalence setting. We conducted a 15 year retrospective cohort study (2010–2024) across two hospitals in Madrid. Patients with microbiologically confirmed TB during cancer treatment or within the preceding 2 years were included. Clinical and demographic variables were analyzed to identify factors associated with adverse outcomes. Eighty-eight cancer patients were diagnosed with TB (median age 62.5 years); 70.5

BACKGROUND:Fluconazole-resistant Candida parapsilosis is a matter of concern. OBJECTIVES:To investigate fluconazole resistance among Candida parapsilosis complex isolates from patients admitted to three Brazilian hospitals, and to characterise resistance mechanisms and clonal relatedness. PATIENTS/METHODS:A total of 76 C. parapsilosis complex isolates were collected from 60 patients hospitalised at three medical centres (H1-H3) located in Vitória, Espírito Santo state (2017-2023). Of these, 38 isolates were obtained from bloodstream cultures, four from catheter tips and 34 from an ICU surveillance study conducted at H1. In vitro susceptibility testing was performed according to the E.Def 7.4 EUCAST method. C. parapsilosis sensu stricto isolates were genotyped using microsatellite markers, and the ERG11 gene was sequenced in resistant isolates. RESULTS:Candida parapsilosis sensu stricto was the most common species (65/76 isolates; 85.5%), followed by C. orthopsilosis (n = 8, 10.5%), and C. metapsilosis (n = 3, 4%). Among the C. parapsilosis sensu stricto isolates, 5/65 (7.7%) were fluconazole-resistant, harboured the G458S ERG11p substitution, and were detected in 2019 and 2020. Only one fluconazole-resistant isolate was also voriconazole-resistant; all isolates were susceptible to the remaining agents. Fluconazole-resistant isolates sourced from H2 were grouped into two unrelated genotypes, and recovered from patients with haematological malignancies, tumours and central nervous system disorders. Only two patients had a history of azole exposure. CONCLUSIONS:This is the first report of fluconazole-resistant C. parapsilosis sensu stricto isolates harbouring the G458S ERG11p substitution in Brazil. Here reported isolates showed resistance to fluconazole alone, which is an unusual pattern among C. parapsilosis sensu stricto isolates harbouring the G458S substitution.

Invasive fungal infections (IFI) pose significant risks to solid organ transplant recipients, especially within the first 180 days post-transplantation. Current European and US guidelines are limited and lack strong evidence. Prophylactic strategies are moving away from universal approaches due to risks like rare fungal infections, adverse effects, drug interactions (especially with immunosuppressants), and higher costs. This study aims to outline current antifungal (AF) prophylaxis practices in solid organ transplant institutions and establish guidelines for managing IFI in this vulnerable patient population. From May 2023 to May 2024, tertiary care institutions were invited to participate in an online questionnaire on AF prophylaxis following solid organ transplantation. The survey gathered data on transplant volumes, incidence of IFI by pathogen, and prophylactic strategies, including triggers, preferred AF, and duration. We analyzed 64 responses from 32 countries, primarily in Europe. Kidney transplants were most frequent, followed by liver transplants, often involving multi-organ procedures. Air quality measures, including air sampling and HEPA filter usage, varied widely, with lung and heart transplant units showing higher adoption rates. AF prophylaxis was consistently used in lung transplants and frequently in liver, bowel, and heart transplants, triggered by factors such as reintervention, organ retransplantation, or Candida spp. colonization. Preferred AF agents varied by organ type, commonly including liposomal amphotericin B, caspofungin, and fluconazole. Breakthrough IFI incidence varied significantly by organ type and specific pathogens, with the majority of institutions reporting dedicated infectious disease teams serving their transplant units. This survey provides a comprehensive overview of current AF prophylaxis practices in solid organ transplantation across diverse institutions. Addressing variability through standardized, evidence-based guidelines is essential for optimizing patient outcomes in managing IFI risks post-transplant. Jon Salmanton-Garcia, MSc, MPH, PhD, menarini, gilead, astrazeneca, pfizer: Honoraria Oliver A. Cornely, Prof. Dr., Al-Jazeera Pharmaceuticals/Hikma: Honoraria|Basilea: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Board Member|Cidara: Grant/Research Support|Elion: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|Grupo Biotoscana/United Medical/Knight: Honoraria|Melinta: Advisor/Consultant|Melinta: Board Member|MSD: Honoraria|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Mundipharma: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pulmocide: Board Member|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria

BACKGROUND:Limited data are available on the performance of non-culture-based diagnostics in hematology patients with febrile neutropenia (FN). METHODS:The European Conference on Infections in Leukaemia (ECIL) 10 group performed a review (2011-2024) on the performance of available in Europe non-culture-based diagnostic methods on blood samples in hematology patients with FN, focusing on bacterial infections. The following tests were included: direct matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), multiplex/specific polymerase chain reaction (PCR), T2-magnetic resonance (T2MR), and metagenomic next generation sequencing (mNGS). A list of 6 predefined pertinent questions was assessed for the performance of each test. RESULTS:For MALDI-TOF-MS, 4/16 (25%) articles were retained, including 475 hematology patients (98 with FN), with sensitivity ranging from 63 to 92.6%. For multiplex-PCR, 8/293 (2.7%) articles were retained, including 509 hematology patients (209 with FN), with a sensitivity of 80.5% and 100% (2 studies) and one study reporting a specificity of 88.5%. For T2MR, 1/18 (5.6%) article was retained including 648 hematology patients (309 with FN) and sensitivity and specificity of 84.2 and 85.9%, respectively. For mNGS, 6/35 (17%) articles were retained: 459 hematology patients (335 with FN), sensitivity (40-100%) and specificity (40-84%) reported in 3 studies. No articles were found on specific PCR in hematology patients. Improved microbiological documentation was reported in 5, 1, and 5 studies on multiplex-PCR, T2MR, and mNGS, respectively. Faster time to diagnosis was reported in 1, 5, and 1 studies on MALDI-TOF-MS, multiplex-PCR, and T2MR, respectively. Treatment choice was affected by the results of MALDI-TOF-MS, multiplex-PCR, mNGS in 1, 6, and 2 studies, respectively. No significant impact on overall survival or length of stay was reported for any of the tests reviewed. CONCLUSIONS:Limited evidence exists on the performance of non-culture-based diagnostics in hematology patients. Blood cultures should be routinely used, even if new tests are available, which should be used in conjunction with the routine microbiological techniques, until more quality data are available.

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.