Search

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.

Objectives: COVID-19 unravelled new ethical issues in the neglected field of infectious diseases ethics (IDE). We investigated IDE involvement among infectious diseases professionals., Methods: A global survey was disseminated during 2021-2022. Responses were stratified by demographics, WHO region, income, and ethics training. A confirmatory factor analysis was used to identify two themes representing IDE relevant areas (theme 1, including stigma, inequity, vulnerability, public health, and global impact) and emerging topics (theme 2, including inequity and research integrity in COVID-19, increased ethics interest, and gaps in IDE). Quantile and logistic regression analyses investigated determinants of ethics themes and responders' ethics attitude., Results: We included 477 participants from 71 countries. Most were females (282/460, 61%) and clinicians (327/457, 72%). Participants advocated further personal (289/443, 65%) or societies' (374/450, 83%) involvement in bioethics. Only 5% (22/477) of respondents claimed to have received enough bioethics training and 28% (114/412) were dissatisfied with it. Dedicated courses or expert case discussion were the preferred ways for receiving education in bioethics. Theme 1 and 2 median values were above 7 (on a 1-10 scale), showing high interest in IDE. Confirmatory factor analysis showed optimal and acceptable fit, respectively. Being from the region of Americas was associated with theme 1, whereas having received bioethics training was associated with both themes. Females and respondents from the Americas and Europe regions reported lower involvement in bioethics activities, whereas those aged between 44 and 54 years and trained in bioethics were more involved. Age above 55 years and nonclinical role were negatively associated with aspiration for further bioethics involvement., Discussion: We identified IDE themes that can inform on gaps in bioethics. Ethics training was associated with interest in IDE and bioethics activities and should be offered to integrate this discipline into daily clinical practice across age, gender, and different areas worldwide., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The FOSFOMIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli, in comparison with other intravenous antimicrobials., Methods: A prospective, multinational matched cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in ten centres from Spain, Italy, and Türkiye. Matching criteria included type of infection acquisition, Charlson and Pitt scores. Endpoints were clinical and microbiological cure, mortality, recurrence, and adverse effects. Analyses used conditional logistic regression and desirability of outcome ranking (DOOR)., Results: Overall, 155 matched pairs were included. Clinical and microbiological cure rates were 65.2% (101/155; 95% CI, 57.4-72.2) and 63.2% (98/155; 95% CI, 55.4-70.4) with fosfomycin and comparators, respectively (adjusted OR, 1.09; 95% CI, 0.68-1.73; p 0.73). Mortality rates were 1.9% (3/155; 95% CI, 0.7-5.5) and 5.8% (9/155; 95% CI, 3.1-10.7), respectively (p 0.11). Recurrence rates were 14.2% (22/155; 95% CI, 9.6-20.6) in the fosfomycin group vs. 10.3% (16/155; 95% CI, 6.1-16.1) (p 0.39). Severe adverse effects occurred in 1.9% (3/155; 95% CI, 0.7-5.5) of patients treated with fosfomycin vs. 0.6% (1/155; 95% CI, 0.0-3.3) in the control group (p 0.62). Non-severe adverse effects were more frequent with fosfomycin, affecting 23.3% (36/155; 95% CI, 17.0-30.7) compared with 7.7% (12/155; 95% CI, 4.1-13.1) in the control group (adjusted OR, 5.36; 95% CI, 2.04-14.1; p < 0.001). In DOOR analysis, fosfomycin demonstrated comparable effectiveness in treating pyelonephritis (probability of better DOOR, 54.0%; 95% CI, 48.5-59.6) and in comparison with ceftriaxone (50.3%; 95% CI, 44.7-55.8), without evidence of inferiority in bacteraemic urinary tract infections (DOOR, 47.3%; 95% CI, 41.7-52.8)., Discussion: Fosfomycin is a viable option for treating cUTIs caused by E. coli, allowing for diversification in the treatment of these high-incidence infections., (Copyright © 2025 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Incorporating ethics into clinical practice guidelines (CPGs) can be challenging. This is particularly evident for infectious diseases (ID) CPGs because of the complexity of ID ethics (IDE) and the multiplicity of populations at risk for infections., Objectives: The OPENING project (IncOrPorating Ethics iN ClINical Guidelines: Practical Indications) was initiated by the European Society of Clinical Microbiology and Infectious Diseases Ethics Advisory Committee in collaboration with the European Society of Clinical Microbiology and Infectious Diseases Guidelines Subcommittee to generate guidelines for the systematic inclusion of ethics principles into ID CPGs., Sources: The first part of the project, presented here, aimed at: (a) performing a scoping review of articles published in PubMed and Google Scholar between 1990 and 2024 discussing ethics inclusion in CPGs; (b) reviewing guidance documents for ethics incorporation in documents from international societies; (c) outlining how the main ethics principles could be included in ID CPGs according to the results retrieved., Content: We retrieved 21 articles written between 1994 and 2024. None of these specifically focused on IDE. The main topic discussed in articles and societies' guidance was the inclusion of equity principles at different stages of CPGs development. Multiple authors also addressed how specific subgroups and disadvantaged populations should be considered in the preparation of CPGs. Involvement of patients and their representatives in CPGs was also advocated. A structured framework for the systematic inclusion of IDE principles in CPGs was suggested to summarize these points., Implications: There is a lack of recommendations for incorporating ethics in ID CPGs. Efforts should be made by scientific societies to include ethics guidelines in ID CPGs to fill this gap., (Copyright © 2025 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Both vancomycin (VAN) and teicoplanin (TEI) augment the risk of acute kidney injury (AKI) when combined with piperacillin-tazobactam (TZP). We aimed to compare the risk of AKI among patients receiving TZP-VAN vs. TZP-TEI., Methods: This was a prospective, multinational, multicentre cohort study conducted in 12 centres from Turkiye, Italy, and Spain between 1 June 2022, and 31 December 2023. The primary outcome was the occurrence of AKI between the first day of antibiotic treatment and the third day after completing therapy, according to the Kidney Disease Improving Global Outcomes criteria. Multivariable logistic regression and propensity-score match analyses were employed to adjust for confounding variables. Stratified Kaplan-Meier analysis was used to assess the time-to-AKI between the comparison groups., Results: Of 187 patients (TZP-TEI, n = 102; TZP-VAN, n = 85), the AKI occurred in 21 patients (24.7%) who received TZP-VAN and in 15 patients (14.7%) with TZP-TEI (unadjusted odds ratio [OR], 1.90; 95% CI: 0.91-3.97; P = 0.087). After adjusting for confounding variables with multivariable analysis, TZP-VAN was not associated with increased odds of AKI compared with TZP-TEI; with an adjusted OR of 2.24 (95% CI: 0.78-6.42; P = 0.133). In propensity-score matched analysis (n = 49 pairs), the AKI risk was similar between the two groups (OR, 2.10; 95% CI: 0.67-6.50; P = 0.199). The stratified Kaplan-Meier analysis indicated no difference between the treatment groups in terms of time-to-AKI (log-rank test, P = 0.107)., Conclusions: The risk of AKI in TZP-VAN was similar to that in TZP-TEI. These results should be confirmed in randomized controlled trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. P.N.A.H. reports a research grant from Gilead, has served on advisory boards for OpGen, Merck, and Sandoz, and has received speakers fees from OpGen, Sandoz, Pfizer, and BioMerieux. M.A. reports research support from Pfizer and Gilead. He was also a member of Data Review Committee of GSK. D.L.P. reports receiving grants from Shionogi, Pfizer, Merck, BioVersys, bioMerieux, Johnson & Johnson, and Gilead and receiving honoraria from Shionogi, Merck, GSK, bioMerieux, Cepheid, Aurobac, Arrepath, Menarini, CARB-X, and the AMR Action Fund. A.C. served as a consultant or advisory board and/or received speaker's fees and/or received research grants for its institutions, outside the present work from Gilead Science, ViiV Healthcare, GSK, Janssen, TILLOTS, Shionogi, and Merck Sharp & Dohme. L.L. reports a consulting fee from Takeda. D.F. received speaker's fee and/or grant for its institution, outside the present work, from GILEAD sciences, ViiV Healthcare, MSD. All other authors have nothing to declare., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There has been an unprecedented increase in the number of immunocompromised (IC) patients in clinical practice due to various reasons. Bacterial infections are a major cause of morbidity and mortality in this population. Emerging antibacterial resistance poses a significant challenge for prophylaxis and treatment., Objectives: We aim to provide an update on antibacterial prophylaxis and management, particularly in high-risk IC patients, including those with acute leukaemia and haematopoietic stem cell transplantation., Sources: We reviewed original articles, systematic reviews, metanalyses, and guidelines using PubMed, Scopus, and Web of Science., Content: We discussed the pros and cons of fluoroquinolone prophylaxis in neutropenic patients in the context of personalized medicine. We also attempted to give an outline of empirical treatment of presumed bacterial infections and targeted therapy options for documented bacterial infections, considering the recent surge of multiresistant bacteria in haematological cancer patients and local epidemiology. The shortcomings of the current strategies and future needs are discussed in detail., Implications: Antibacterial prophylaxis with fluoroquinolones may still have a role in preventing bacterial infections in carefully selected patients with high-risk haematology. Empirical treatment algorithms still need to be adjusted according to host and local factors. The use of rapid diagnostic methods may lessen the need for broad-spectrum empirical antibiotic usage. However, these tests may not be easily available due to budget constraints in countries with limited resources but high rates of bacterial resistance. Although new antimicrobials provide opportunities for effective and less toxic treatment of highly resistant bacterial infections, large-scale data from IC patients are very limited. Using data-driven approaches with artificial intelligence tools may guide the selection of appropriate patients who would benefit most from such prophylactic and treatment regimens., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Chronic granulomatous disease (CGD) is a congenital disorder impairing phagocyte function, causing recurrent, life-threatening infections, and is rarely seen in adulthood. We present a 36-year-old male initially diagnosed with pneumonia. Bronchoalveolar lavage and blood cultures yielded Burkholderia multivorans/cepacia complex, sputum cultures Aspergillus niger . Despite the antimicrobial treatment, his condition deteriorated. His clinical and laboratory findings indicated hemophagocytic lymphohistiocytosis. He responded to steroids. Nitroblue tetrazolium and dihydroergotamine-123 tests confirmed CGD. Whole exome sequencing identified NCF1 deletion. He received interferon-gamma, voriconazole, and trimethoprim-sulfamethoxazole. Allogeneic hematopoietic stem cell transplantation was planned. This case report improves understanding of CGD in adults, aiming to enhance diagnostic and therapeutic strategies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Infectious Diseases and Clinical Microbiology.)

Although occult fungal, viral, and multidrug-resistant bacterial infections can cause persistent fever in neutropenic patients with hematologic cancer, a variety of noninfectious entities should be considered on a case-by-case basis in the context of negative diagnostic workup for infection., Competing Interests: Potential conflicts of interest. M. A. reports research support from Pfizer and Gilead, and was also a member of the data review committee of GSK. D. P. K. reports honoraria and research support from Gilead Sciences and Astellas Pharma; received consultant fees from Astellas Pharma, Merck, Gilead Sciences, and Knight; and is a member of the data review committee of Cidara Therapeutics, AbbVie, Scynexis, and the Mycoses Study Group. A. T. A. reports no potential conflicts of interest. 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.)

Introduction: Patients with hematological malignancies (PHMs) are at increased risk for infections caused by carbapenem-resistant organisms (CROs) due to frequent exposure to broad-spectrum antibiotics and prolonged hospital stays. These infections result in high mortality and morbidity rates along with delays in chemotherapy, longer hospitalizations, and increased health care costs., Areas Covered: Treatment alternatives for CRO infections in PHMs., Expert Opinion: The best available treatment option for KPC and OXA-48 producers is ceftazidime/avibactam. Imipenem/cilastatin/relebactam and meropenem/vaborbactam remain as the alternative options. They can also be used as salvage therapy in KPC-positive Enterobacterales infections resistant to ceftazidime/avibactam, if in vitro susceptibility is shown. Treatment of metallo-β-lactamase producers is an unmet need. Ceftazidime/avibactam plus aztreonam or aztreonam/avibactam seems to be the most reliable option for metallo-β-lactamase producers. As a first-line option for carbapenem-resistant Pseudomonas aeruginosa infections, ceftolozane/tazobactam is preferable and ceftazidime/avibactam and imipenem/cilastatin/relebactam constitute alternative regimens. Although sulbactam/durlobactam is the most reliable option against carbapenem-resistant Acinetobacter baumannii infections, its utility as monotherapy and in PHMs is not yet known. Cefiderocol can be selected as a 'last-resort' option for CRO infections. New risk score models supported by artificial intelligence algorithms can be used to predict the exact risk of infections in previously colonized patients.

Objectives: We aimed to evaluate the prevalence and perception of scientific misconduct in infectious diseases (ID) and clinical microbiology (CM), as reported by the ID/CM community., Methods: An anonymous online European Society of Clinical Microbiology and Infectious Diseases survey circulated among society members from October 2023 to June 2024; the questionnaire included data on participants' views on their own and their colleagues' scientific misconduct in the last 5 years., Results: The survey received 220 responses. Responders were 73% ID physicians, 52% men, 56% aged 35-54 years, and represented 48 countries, mainly European (126 participants). The vast majority of participants (78%) reported that they did not personally commit scientific misconduct, whereas 54% reported witnessing misconduct by colleagues in their field. The most commonly committed misconduct by both responders and their colleagues was misconduct of authorship rules, 14% and 41%, respectively. Overall, 18% reported witnessing misleading reporting and 14% reported witnessing nonaccurate reporting of conflict of interest. Nevertheless, the majority (>60%) of responders reported high confidence in the integrity of published work in the field of ID/CM. Approximately one-third of responders were not aware of the European Society of Clinical Microbiology and Infectious Diseases ethics advisory committee as an authority to which members can report misconduct., Discussion: Scientific misconduct, mostly related to violation of authorship rules, seems to be common in ID/CM. Efforts to improve scientific integrity should be made to keep trust in the scientific process., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Bacterial infections frequently occur in haematological patients, especially during prolonged neutropenia after intensive chemotherapy, often leading to bloodstream infections and pneumonia., Objective: Routine antimicrobial prophylaxis (AMP) for high-risk haematology patients is still debated while prevalence of multi-drug resistant (MDR) Gram-negative bacteria (GNB) is rising globally. We aimed to assess the current practice of AMP in this population., Design: Cross-sectional observational survey study., Methods: Haematologists and infectious diseases physicians Europewide were invited to an online survey including questions on routine screening for GNB, incidence of MDR-GNB colonization, antimicrobial prophylaxis practices, rates of bloodstream infections (BSI), ICU admission and mortality differentiated by infections due to GNB versus MDR-GNB., Results: 120 haematology centres from 28 countries participated. Screening for MDR-GNB is performed in 86.7% of centres, mostly via rectal swabs (58.3%). In 39.2% of routine AMP is used, mostly with fluoroquinolones. Estimates of GNB-BSI yielded higher rates in patients not receiving anti-GNB prophylaxis than in those who do for E. coli (10% vs 7%) Klebsiella spp. (10% vs 5%), and Pseudomonas spp. (5% vs 4%). Rates for MDR-GNB infection were estimated lower in centres that administer AMP for MDR E. coli (5% vs 3%) Klebsiella spp. (5% vs 3%), and Pseudomonas spp. (2% vs 1%). In an exploratory analysis, Southern and Eastern European countries expected higher rates of MDR-GNB infections with lower ICU admission and mortality rates which may be subject to estimation bias., Conclusion: Screening for MDR-GNB is frequently performed. AMP against GNB infections is still often implemented. Estimated BSI rates are rather low, while the rate of MDR-GNB infections rises. Tailored prophylaxis including antimicrobial stewardship becomes more important., (© The Author(s), 2024.)

Acinetobacter baumannii , a notable drug-resistant bacterium, often induces severe infections in healthcare settings, prompting a deeper exploration of treatment alternatives due to escalating carbapenem resistance. This study meticulously examined clinical, microbiological, and molecular aspects related to in-hospital mortality in patients with carbapenem-resistant A . baumannii (CRAB) bloodstream infections (BSIs). From 292 isolates, 153 cases were scrutinized, reidentified through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and evaluated for antimicrobial susceptibility and carbapenemase genes via multiplex polymerase chain reaction (PCR). Utilizing supervised machine learning, the study constructed models to predict 14- and 30-day mortality rates, revealing the Naïve Bayes model's superior specificity (0.75) and area under the curve (0.822) for 14-day mortality, and the Random Forest model's impressive recall (0.85) for 30-day mortality. These models delineated eight and nine significant features for 14- and 30-day mortality predictions, respectively, with "septic shock" as a pivotal variable. Additional variables such as neutropenia with neutropenic days prior to sepsis, mechanical ventilator support, chronic kidney disease, and heart failure were also identified as ranking features. However, empirical antibiotic therapy appropriateness and specific microbiological data had minimal predictive efficacy. This research offers foundational data for assessing mortality risks associated with CRAB BSI and underscores the importance of stringent infection control practices in the wake of the scarcity of new effective antibiotics against resistant strains. The advanced models and insights generated in this study serve as significant resources for managing the repercussions of A . baumannii infections, contributing substantially to the clinical understanding and management of such infections in healthcare environments., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gökhan Metan received honoraria for speaking at symposia and lectures organized by Gilead Merck, Sharp, and Dohme (MSD), and Pfizer, as well as a consultation fee from the United Nations Turkey Office. He has also received travel grants from MSD, Pfizer, and Gilead to participate in conferences. Other authors declare that they have no competing interests.

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients)., Methods: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied., Results: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment., Conclusions: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline's release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients ( p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.

Objectives: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years., Methods: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days., Results: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%)., Conclusions: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age., Competing Interests: Declarations of competing interest JS has received research grants by the German Federal Ministry of Education and Research (BMBF), Noscendo and Basilea Pharmaceuticals; has received speaker honoraria by AbbVie, Hikma, Pfizer and Gilead; has been a consultant to Gilead, Produkt&Markt GmbH, Alvea Vax and Micron Research and has received travel grants by German Society for Infectious Diseases (DGI) and Meta-Alexander Foundation, all outside the submitted work. MA has received research grants from Pfizer and Gilead. Contributed to educational activities organized/supported by Pfizer, Roche, Gilead, GSK, Moderna and Sanofi. All honoraria from these activities are paid to the Institution. JSG has received speaker honoraria from Gilead and Pfizer, outside of the submitted work. MZ has received honoraria for lecturing courses by Pfizer Malaysia; is now an employee with AiCuris AG. RS has received lecture honoraria from Pfizer and Hikma, outside of the submitted work. JFI has received research grants by the Instituto de Salud Carlos III, Ministry of Science. Spain has received grants or research contracts from Laboratorios Faes, Normon, Pfizer, Italfarmaco, GSK, Prestige; has been a consultant or has received speaker honoraria from Faes, Normon, Cinfa, Mundipharma, Abbott, Novartis, and collaborations from AbbVie. PWGM has received honoraria and/or grant funding from Gilead, Janssen, MSD, ViiV Healthcare, GSK, and AstraZeneca, outside of the submitted work. SMK has received grants from Pfizer, MSD, Huvepharma, AiCuris, Astra Zeneca, Mylan, Janssen pharma. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from AbbVie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pfizer, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, AbbVie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, Shionogi; payment for expert testimony from Cidara; participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, and The Prime Meridian Group. Kristin G-I Mohn has received honoraria for lectures from Takeda, IQVIA and BioNTech, has received a Research Grant from Norwegian Regional Health authorities, West, grant nr F12626 and is a Member of an advisory board on committee for National vaccination programs, Norwegian Public Health Institute. The remaining authors have no competing interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections., Methods: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed., Results: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004)., Conclusions: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: The authors do not declare conflicts of interest related to the submitted manuscript. The funder of the study (Scynexis) had no role in study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI)., Methods: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators., Results: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality., Conclusion: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients., (© 2024. The Author(s).)

Background: Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality., Methods: Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model., Results: Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045)., Conclusions: Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium., (© 2024. The Author(s).)

Purpose: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs)., Methods: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method., Results: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies., (© 2024. The Author(s).)

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Objectives: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study., Methods: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied., Results: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24)., Discussion: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data. A core reporting dataset consisting of category, site, severity, organism, and endpoints was developed as a minimum standard for reporting of infection events in immunocompromised patients across study types. Further additional information is recommended depending on study type. The standardised reporting of infectious events and attributable complications in immunocompromised patients will improve diagnostic, treatment, and prevention approaches and facilitate future research in this patient group., Competing Interests: Declaration of interests BWT has received grants from Seqirus and MSD, and has been on the advisory board for Takeda, CSL-Behring, and Moderna. RdlC has consulted for Moderna and AstraZeneca, and received honoraria from MSD, Shionogi, Astellas, Moderna, Atara, Pfizer, and Gilead. HHH has consulted for Molecular Partners, Roche, and Vero Tx, and received honoraria from Gilead, MSD, and Vero Tx. LO-Z has received grants from Scynexis, Pulmocide, Gilead, Astellas, Pfizer, T2, and the National Institutes of Health, and has consulted for F2G, GSK, Melinta, Pfizer, Viracor, Cidara, and Gilead. BHT is on the advisory board for Pfizer and MSD. RMLH is on the advisory board for Takeda. PAG has consulted for MSD, Allovir, and Takeda; received honoraria from MSD, Atara, Takeda, and Gilead; and is on the data safety and monitoring and advisory boards for Reithera. NJM has received a grant from the Swiss National Science Foundation and meeting support from Bio Test and Pfizer. MAS has received grants from Gilead, MSD, and F2G. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

Background: Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially for people of advanced age, however, optimal dosing regimens are as yet lacking., Methods: EU-COVAT-1-AGED Part A is a randomised controlled, adaptive, multicentre phase II trial evaluating safety and immunogenicity of a 3rd vaccination (1st booster) in individuals ≥75 years. Fifty-three participants were randomised to full-doses of either mRNA-1273 (Spikevax®, 100 µg) or BNT162b2 (Comirnaty®, 30 µg). The primary endpoint was the rate of 2-fold circulating antibody titre increase 14 days post-vaccination measured by quantitative electrochemiluminescence (ECL) immunoassay, targeting RBD region of Wuhan wild-type SARS-CoV-2. Secondary endpoints included the changes in neutralising capacity against wild-type and 25 variants of concern at 14 days and up to 12 months. Safety was assessed by monitoring of solicited adverse events (AEs) for seven days after on-study vaccination. Unsolicited AEs were collected until the end of follow-up at 12 months, SAEs were pursued for a further 30 days., Results: Between 08th of November 2021 and 04th of January 2022, 53 participants ≥75 years received a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n = 25/mRNA-1273 n = 25) were included in the analyses for immunogenicity at day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days after vaccination was reached for all subjects. A 3rd vaccination of full-dose mRNA-1273 provided higher anti-RBD IgG titres (Geometric mean titre) D14 mRNA-127310711 IU/mL (95 %-CI: 8003;14336) vs. BNT162b2: 7090 IU/mL (95 %-CI: 5688;8837). We detected a pattern showing higher neutralising capacity of full-dose mRNA-1273 against wild-type as well as for 23 out of 25 tested variants., Interpretation: Third doses of either BNT162b2 or mRNA-1273 provide substantial circulating antibody increase 14 days after vaccination. Full-dose mRNA-1273 provides higher antibody levels with an overall similar safety profile for people ≥75 years., Funding: This trial was funded by the European Commission (Framework Program HORIZON 2020)., Competing Interests: Declaration of Competing Interest JN no conflicts declared. JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals; has received speaker honoraria by AbbVie, Pfizer and Gilead; has been a consultant to Gilead, Produkt & Markt GmbH, Alvea Vax and Micron Research and has received travel grants by German Society for Infectious Diseases (DGI) and Meta-Alexander Foundation. AJC no conflicts declared. JFI has received research grants by the Instituto de Salud Carlos III, Ministry of Science. Spain. Has received grants or research contracts from Laboratorios Faes, Normon, Pfizer, Italfarmaco, GSK, Prestige, has been a consultant or has received speaker honoraria from Faes, Normon, Cinfa, Mundipharma, Abbott, Novartis and docency colaborations from Abbvie. MA has received research grants from Pfizer and Gilead. Contributed to educational activities organized/supported by Pfizer, Roche, Gilead, GSK, Moderna and Sanofi. All honoraria from these activities are paid to the Institution. UB no conflicts declared. SH no conflicts declared. JSG has received speaker honoraria from Gilead and Pfizer, outside of the submitted work. LT no conflicts declared. MZ has received honoraria for lecturing courses by Pfizer Malaysia; is now an employee with AiCuris AG. AC no conflicts declared. JG no conflicts declared. AGL no conflicts declared. PM has received honoraria from Gilead and AstraZeneca, outside of the submitted work. RN no conflicts declared. CG no conflicts declared. GS no conflicts declared. AH no conflicts declared. SKS no conflicts declared. KL no conflicts declared. CL no conflicts declared. HG no conflicts declared. SMK has received grants from Pfizer, MSD, Huvepharma, AiCuris, Astra Zeneca, Mylan, Janssen pharma. FK no conflicts declared. LY no conflicts declared. MP no conflicts declared. PK reports grants or contracts from German Federal Ministry of Research and Education (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine (NUM) and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pfizer, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Abbvie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, Shionogi; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi, The Prime Meridian Group; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Stocks from CoRe Consulting, EasyRadiology; Other interests from DGHO, DGI, ECMM, EHA, ISHAM, MSG-ERC, Wiley., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria., Methods: A unique collection ( n  = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes., Results: Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively., Conclusions: Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.

Objectives: To uncover clinical epidemiology, microbiological characteristics and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs) in Turkish ICU patients., Methods: The EUROBACT II was a prospective observational multicontinental cohort study. We performed a subanalysis of patients from 24 Turkish ICUs included in this study. Risk factors for mortality were identified using multivariable Cox frailty models., Results: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78]. Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599), 67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp. and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329), SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI 1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08), COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality. However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI 1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality, whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with survival., Conclusions: Considering high antimicrobial resistance rate, importance of source control and availability of clinical pharmacists, a multifaceted management programme should be adopted in Turkish ICUs., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines., Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process., Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus., Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VACCELERATE Consortium reports financial support was provided by European Union. VACCELERATE Consortium reports financial support was provided by Federal Ministry of Education and Research Bonn Office., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To understand current practice in terms of duration of antibiotic treatment and timing of intravenous (IV) to oral switching for common bacteraemic conditions amongst infectious diseases (ID) and intensive care unit (ICU) physicians., Methods: An online survey consisting of 18 questions comprising five common clinical bacteraemia scenarios [adapted from the original survey designed by the University of Toronto (Toronto, Ontario, Canada)] was conducted amongst Turkish ID and ICU physicians between November 2020 and November 2021., Results: In total, 236 physicians (76.5% ID and 17.5% ICU) responded. The most commonly recommended duration of antibiotic treatment for bacteraemia was 14 days (42%), followed by 10 (27%) and 7 (18%) days. The median recommended treatment durations were 10 [interquartile range (IQR) 10-14] days for central-venous-catheter-associated bloodstream infection, 10 (IQR 7-14) days for bacteraemic pneumonia, 14 (IQR 10-14) days for bacteraemic urinary tract and intra-abdominal infections, and 14 (IQR 7-14) days for bacteraemic skin and soft tissue infection. Carbapenem resistance influenced the recommendations, but pathogen type did not. No significant difference in responses for most scenarios was found between ID and ICU physicians. Switching to oral antibiotics after a median duration of 7 (IQR 5-7) days of IV treatment was considered by 80% of respondents., Conclusion: Prolonged treatment was recommended for most clinical scenarios. Extended IV durations were recommended before oral switching. A presumption that resistant bacterial infections require longer therapy may be responsible for prolonged treatment durations., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)