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Intro: Published data is limited in describing clinical features and disease burden of invasive Escherichia coli disease (IED). This study characterized bacteremic and non-bacteremic IED in relation to clinical features and multidrug resistance (MDR) of causative E. coli isolates. Methods: EXPECT-2 (NCT04117113) was a multinational, hospital-based, observational study that prospectively enrolled IED patients aged ≥60 years between October 2019 and January 2021. IED was defined by a positive E. coli culture from blood (bacteremic IED), a sterile body site or urine (non-bacteremic IED) in the presence of requisite criteria of Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick SOFA (qSOFA). In-hospital mortality and IED-related medical encounters were assessed through 28 days following IED diagnosis. MDR was defined as acquired non-susceptibility to ≥1 antibiotic in ≥3 antimicrobial classes. Findings: The full analysis set included 193 bacteremic (80.4%) and 47 non- bacteremic (19.6%) patients. Patient demographics were balanced between bacteremic and non-bacteremic IED. The rates of patients with ≥2 SIRS criteria were comparable between bacteremic (64.8%) and non-bacteremic IED (70.2%). The rates of patients with the ≥2-point change in total SOFA score were comparable between bacteremic (62.2%) and non-bacteremic IED (53.2%). The rates of sepsis and septic shock were 75.0% and 11.4%, respectively, for bacteremic, and 83.3% and 7.1%, respectively, for non-bacteremic IED. The most common IED-related medical encounter was the emergency room both in patients with bacteremic (31.5%, [41/130]) and non-bacteremic IED (35.9%, [14/39]). Of 11 patients who died, 6 (54.5%) had bacteremic IED. Of 294 E. coli isolates with antimicrobial susceptibility testing collected from 238 patients, MDR rates were 34.7% (87/251) for bacteremic and 37.2% (16/43) for non-bacteremic isolates. Conclusion: IED manifested as severe infection, with approximately one-third of E. coli isolates displaying MDR. Bacteremic and non-bacteremic IED were characterized by similar clinical features and MDR phenotypes.

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

Abstract Despite remarkable developments in the use of surgical techniques, ergonomic advancements in the operating room, and implementation of bundles, surgical site infections (SSIs) remain a substantial burden, associated with increased morbidity, mortality and healthcare costs. National and international recommendations to prevent SSIs have been published, including recent guidelines by the World Health Organization, but implementation into clinical practice remains an unresolved issue. SSI improvement programs require an integrative approach with measures taken during the pre-, intra- and postoperative care from the numerous stakeholders involved. The current SSI prevention strategies have focused mainly on the role of healthcare workers (HCWs) and procedure related risk factors. The importance and influence of patient participation is becoming an increasingly important concept and advocated as a means to improve patient safety. Novel interventions supporting an active participative role within SSI prevention programs have not been assessed. Empowering patients with information they require to engage in the process of SSI prevention could play a major role for the implementation of recommendations. Based on available scientific evidence, a panel of experts evaluated options for patient involvement in order to provide pragmatic recommendations for pre-, intra- and postoperative activities for the prevention of SSIs. Recommendations were based on existing guidelines and expert opinion. As a result, 9 recommendations for the surgical patient are presented here, including a practice brief in the form of a patient information leaflet. HCWs can use this information to educate patients and allow patient engagement.

Background: Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2., Methods: A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting., Results: Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18-0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32-0.83), and extended-spectrum β-lactamase (ESBL)-producing isolate (aOR = 0.28; 95% CI = 0.17-0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56-3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39-2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09-1.06). Matched and inverse probability treatment weighting analysis showed similar results., Conclusions: These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients., Methods: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis., Results: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p < .001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p = .001) were factors independently associated with recurrence., Conclusions: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GT received honoraria for educational meetings by Shionogi and participated to scientific board for MSD. MF received unconditional grants from MSD, Gilead and speaker honoraria from Shionogi, Pfizer, Menarini, MSD, Gilead, GSK, MundiPharma and TermoFisher. Declared conflicts of interest are outside the submitted work and did not affect the scientific objectivity of this study. The other authors have none to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America (IDSA). In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach., Competing Interests: Potential conflicts of interest. Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate, Inc, and serves on an Agency for Healthcare Research and Quality technical expert panel for diagnosis of acute right lower quadrant abdominal pain (suspected acute appendicitis). J. R. B. serves as past president of the European Society of Clinical Microbiology and Infectious Diseases. M. S. E. receives royalties from UpToDate, Inc, as co-section editor of Pediatric Infectious Diseases. M. K. H. serves on the Society for Healthcare Epidemiology of America (SHEA) Board of Directors. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach., Competing Interests: Potential conflicts of interest. Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate, Inc. J. R. B. serves as past president of the European Society of Clinical Microbiology and Infectious Diseases. M. S. E. receives royalties from UpToDate, Inc, as co-section editor of Pediatric Infectious Diseases. M. K. H. serves on the Society for Healthcare Epidemiology of America (SHEA) Board of Directors. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this guideline, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach., Competing Interests: Potential conflicts of interest. Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate, Inc; serves on an Agency for Healthcare Research and Quality technical expert panel for diagnosis of acute right lower quadrant abdominal pain (suspected acute appendicitis); and has served as an advisor for GenMark Diagnostics, Inc, on molecular diagnostics for gastrointestinal pathogens. J. R. B. serves as past president of ESCMID. M. S. E. receives royalties from UpToDate, Inc, as co–section editor of Pediatric Infectious Diseases. M. K. H. serves on the Society for Healthcare Epidemiology of America Board of Directors and has received free services from OpGen, Inc, for a research project. R. H. is an advisor for bioMérieux, Inc, and was previously an employee of Accelerate Diagnostics, Inc; has received research funding from bioMérieux, Inc; and has served as an advisor for Thermo Fisher Scientific, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based on evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach., Competing Interests: Potential conflicts of interest. Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate, Inc. J. R. B. serves as past president of the European Society of Clinical Microbiology and Infectious Diseases. M. S. E. receives royalties from UpToDate, Inc. as co-section editor of Pediatric Infectious Diseases. M. K. H. serves on the Society for Healthcare Epidemiology of America Board of Directors. All other authors report no relevant disclosures. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this article, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach., Competing Interests: Potential conflicts of interest. Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate and serves on an Agency for Healthcare Research and Quality technical expert panel for diagnosis of acute right lower quadrant abdominal pain (suspected acute appendicitis). M. S. E. receives royalties from UpToDate, as co-section editor of Pediatric Infectious Diseases. M. K. H. serves on the board of directors for the Society for Healthcare Epidemiology of America. J. R. B. serves as past president of the European Society of Clinical Microbiology and Infectious Diseases. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach., Competing Interests: Potential conflicts of interest . Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate, Inc.; serves on an Agency for Healthcare Research and Quality technical expert panel for diagnosis of acute right lower quadrant abdominal pain (suspected acute appendicitis); and has served as an advisor for GenMark Diagnostics, Inc. on molecular diagnostics for gastrointestinal pathogens. J. R. B. serves as past president of the European Society of Clinical Microbiology and Infectious Diseases. M. S. E. receives royalties from UpToDate, Inc. as co-section editor of Pediatric Infectious Diseases. M. K. H. serves on the Society for Healthcare Epidemiology of America (SHEA) Board of Directors and has received free services from OpGen, Inc. for a research project. R. H. is an advisor for bioMerieux, Inc. and was previously an employee of Accelerate Diagnostics, Inc.; has received research funding from bioMerieux, Inc.; and served as an advisor for Thermo Fisher Scientific, Inc. All other authors reported no relevant disclosures. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents 21 updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach., Competing Interests: Potential conflicts of interest. Evaluation of relationships as potential conflicts of interest (COIs) is determined by a review process. The assessment of disclosed relationships for possible conflicts of interest is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). A. W. C. receives honoraria from UpToDate, Inc.; serves on an Agency for Healthcare Research and Quality technical expert panel for diagnosis of acute right lower quadrant abdominal pain (suspected acute appendicitis); and has served as an advisor for GenMark Diagnostics, Inc. on molecular diagnostics for gastrointestinal pathogens. J. R. B. serves as past president of the European Society of Clinical Microbiology and Infectious Diseases. M. S. E. receives royalties from UpToDate, Inc. as co-section editor of Pediatric Infectious Diseases. M. H. serves on the Society Healthcare Epidemiology of America Board of Directors and has received free services from OpGen, Inc. for a research project. R. H. is an advisor for bioMérieux, Inc. and was previously an employee of Accelerate Diagnostics, Inc.; has received research funding from bioMérieux, Inc.; and served as an advisor for Thermo Fisher Scientific, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purposes: Enterococcal BSI is associated with significant morbidity and mortality, with fatality rates of approximately 20-30%. There are microbiological and clinical differences between E. faecalis and E. faecium infections. The aim of this study was to investigate differences in predisposing factors for E. faecalis and E. faecium BSI and to explore prognostic factors., Methods: This study was a post-hoc analysis of PROBAC, a Spanish prospective, multicenter, cohort in 2016-2017. Patients with E. faecalis or E. faecium BSI were eligible. Independent predictors for BSI development in polymicrobial and monomicrobial BSI and in-hospital mortality in the monomicrobial group were identified by logistic regression., Results: A total of 431 patients were included. Independent factors associated with E. faecium BSI were previous use of penicillins (aOR 1.99 (95% CI 1.20-3.32)) or carbapenems (2.35 (1.12-4.93)), hospital-acquired BSI (2.58 (1.61-4.12)), and biliary tract source (3.36 (1.84-6.13)), while congestive heart failure (0.51 (0.27-0.97)), cerebrovascular disease (0.45 (0.21-0.98)), and urinary tract source (0.49 (0.26-0.92)) were associated with E. faecalis BSI. Independent prognostic factors for in-hospital mortality in E. faecalis BSI were Charlson Comorbidity Index (1.27 (1.08-1.51)), SOFA score (1.47 (1.24-1.73)), age (1.06 (1.02-1.10)), and urinary/biliary source (0.29 (0.09-0.90)). For E. faecium BSI, only SOFA score (1.34 (1.14-1.58) was associated with in-hospital mortality., Conclusions: The factors associated with E. faecium and E. faecalis BSI are different. These variables may be helpful in the suspicion of one or other species for empiric therapeutic decisions and provide valuable information on prognosis., (© 2024. The Author(s).)

Objectives: This study aimed to determine the association of Escherichia coli microbiological factors with 30-day mortality in patients with bloodstream infection (BSI) presenting with a dysregulated response to infection (i.e. sepsis or septic shock)., Methods: Whole-genome sequencing was performed on 224 E coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance, and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI)., Results: Mortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02-1.07), Charlson index ≥3 (1.78; 0.95-3.32), urinary BSI source (0.30; 0.16-0.57), and active empirical treatment (0.36; 0.11-1.14) with an AUROC of 0.73 (95% CI, 0.67-0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94-14.04), eilA gene (2.62; 1.14-6.02), and astA gene (2.39; 0.87-6.59) as associated with mortality, with an AUROC of 0.76 (0.69-0.82)., Discussion: Despite having a modest overall contribution, some microbiological factors were associated with increased odds of death and deserve to be studied as potential therapeutic or preventive targets., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Bloodstream infections (BSI) are an important cause of mortality, although they show heterogeneity depending on patients and aetiological factors. Comprehensive and specific mortality scores for BSI are scarce. The objective of this study was to develop a mortality predictive score in BSI based on a multicentre prospective cohort., Methods: A prospective cohort including consecutive adults with bacteraemia recruited between October 2016 and March 2017 in 26 Spanish hospitals was randomly divided into a derivation cohort (DC) and a validation cohort (VC). The outcome was all-cause 30-day mortality. Predictors were assessed the day of blood culture growth. A logistic regression model and score were developed in the DC for mortality predictors; the model was applied to the VC., Results: Overall, 4102 patients formed the DC and 2009 the VC. Mortality was 11.8% in the DC and 12.34% in the CV; the patients and aetiological features were similar for both cohorts. The mortality predictors selected in the final multivariate model in the DC were age, cancer, liver cirrhosis, fatal McCabe underlying condition, polymicrobial bacteraemia, high-risk aetiologies, high-risk source of infection, recent use of broad-spectrum antibiotics, stupor or coma, mean blood pressure <70 mmHg and PaO2/FiO2 ≤ 300 or equivalent. Mortality in the DC was <2% for ≤2 points, 6%-14% for 3-7 points, 26%-45% for 8-12 points and ≥60% for ≥13 points. The predictive score had areas under the receiving operating curves of 0.81 (95% CI 0.79-0.83) in the DC and 0.80 (0.78-0.83) in the VC., Conclusions: A 30 day mortality predictive score in BSI with good discrimination ability was developed and internally validated., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The early initiation of the empirical antibiotic treatment and its impact on mortality in patients with bacteraemia has been extensively studied. However, information on the impact of precocity of the targeted antibiotic treatment is scarce. We aimed to study the impact of further delay in active antibiotic therapy on 30-day mortality among patients with bloodstream infection who had not received appropriate empirical therapy., Design: We worked with PROBAC cohort (prospective and compound by patients from 26 different Spanish hospitals). We selected a total of 1703 patients, who survived to day 2 without having received any active antibiotic therapy against the causative pathogen., Results: The 30-day mortality was 14% (238 patients). The adjusted odds of mortality increased for every day of delay, from 1.53 (95% confidence interval (CI) 1.13-2.08) for day 3 or after to 11.38 (95% CI 7.95-16.38) for day 6 or after., Conclusion: We concluded that among patients who had not received active treatment within the first 2 days of blood culture collection, additional delays in active targeted therapy were associated with increased mortality. These results emphasize the importance of active interventions in the management of patients with bloodstream infections., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns of causative E. coli isolates in older adults., Methods: EXPECT-2 (NCT04117113) was a prospective, observational, multinational, hospital-based study conducted in patients with IED aged ≥ 60 years. IED was determined by the microbiological confirmation of E. coli from blood; or by the microbiological confirmation of E. coli from urine or an otherwise sterile body site in the presence of requisite criteria of systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick SOFA (qSOFA). The primary outcomes were the clinical presentation of IED and AMR rates of E. coli isolates to clinically relevant antibiotics. Complications and in-hospital mortality were assessed through 28 days following IED diagnosis., Results: Of 240 enrolled patients, 80.4% had bacteremic and 19.6% had non-bacteremic IED. One-half of infections (50.4%) were community-acquired. The most common source of infection was the urinary tract (62.9%). Of 240 patients, 65.8% fulfilled ≥ 2 SIRS criteria, and 60.4% had a total SOFA score of ≥ 2. Investigator-diagnosed sepsis and septic shock were reported in 72.1% and 10.0% of patients, respectively. The most common complication was kidney dysfunction (12.9%). The overall in-hospital mortality was 4.6%. Of 299 E. coli isolates tested, the resistance rates were: 30.4% for trimethoprim-sulfamethoxazole, 24.1% for ciprofloxacin, 22.1% for levofloxacin, 16.4% for ceftriaxone, 5.7% for cefepime, and 4.3% for ceftazidime., Conclusions: The clinical profile of identified IED cases was characterized by high rates of sepsis. IED was associated with high rates of AMR to clinically relevant antibiotics. The identification of IED can be optimized by using a combination of clinical criteria (SIRS, SOFA, or qSOFA) and culture results., (© 2024. The Author(s).)

Background: Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study., Methods: Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome., Results: Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results., Conclusions: Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI., (© 2024. The Author(s).)

Background: Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec)., Methods: A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality., Results: Overall, 386 patients were included (363 [94%] with CP-Kp and 23 [6%] CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21-13.19)., Conclusions: HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE., (© 2024. The Author(s).)

Background: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection., Methods: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77)., Findings: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29)., Interpretation: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy., Funding: Deutsche Forschungsgemeinschaft., Translations: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AJK received funding for this study from the Deutsche Forschungsgemeinschaft and is Chairperson of the German Sepsis Society. HSe received grants or research support from the Bundesministerium für Bildung und Forschung (BMBF) Germany and the German Center for Infection Research, and has been a consultant for Debiopharm, Gilead, MSD, and Shionogi. AS has received grants from Gilead Sciences (IN-ES-540–6089) and Pfizer, consulting fees and lecture honoraria from Pfizer, MSD, Angelini, Shionogi, Gilead, and Menarini, and travel support from Pfizer. JR-B has received grants or research support from the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/00001) and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC, CB21/13/00012), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, which are co-financed by the European Development Regional Fund. SH received honoraria and travel support from Shionogi, Pfizer, Infectopharm, and AdvanzPharma. NJ reports receiving honoraria for lectures from AbbVie, Bayer, Infectopharm, and Medacta, travel support from Gilead, Pfizer, and Correvio, participation in paid advisory board meetings for MSD, and membership in the steering committee of the German Society of Internal Medicine. SRi received honoraria for lectures from Falk Foundation, Pfizer, bioMérieux, Akademie für Infektionsmedizin, Med Update, streamedup!, and Deutscher Apotheker-Verlag. TW reports receiving honoraria for presentations from AstraZeneca, Advanz, MSD, Pfizer, and Shionogi, grants or research support from BMBF Germany, and travel support from Pfizer. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates., Objectives: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae., Methods: The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time-kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MIC ≤ 16 mg/L) and three as resistant (MIC > 16 mg/L). The HFIM was performed over 3 days to mimic human-like pharmacokinetics of 2 g q8h. Bacterial counts were performed by plating on Mueller-Hinton agar (MHA) and MHA containing 64 mg/L temocillin to detect resistant subpopulations., Results: All isolates showed a reduction in bacterial population of at least 3 log cfu/mL within the first 8 h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values., Conclusions: These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30 min may be inadequate to prevent the emergence of resistant variants., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions., Methods: E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons., Findings: We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably bla CTX-M-15 and bla OXA-1 ., Interpretation: In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection., Funding: Instituto de Salud Carlos III., Competing Interests: Declaration of interests LEL-C reports payments as a speaker from Angelini Pharm and Correvio Pharma Corp. PR-G reports consulting fees from and participation on a data safety monitoring board or advisory board for Advanz Pharma, support for attending meetings or travel from Gilead Sciences, and payments for presentations from Menarini Group and Shionogi & Co. LB-P reports payments for presentations in educational events from Tillotts Pharma and Menarini Group and support for attending meetings or travel from Pfizer. JMR-I reports payments as a speaker from Pfizer and Shionogi & Co. AG-M reports support for attending ECCMID 2022 from ESCMID. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)