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The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing bacteriolytic activities against 81.3% (n = 26) and 78.1% (n = 25) of 32 XDR carbapenemase-producing colistin-resistant K. pneumoniae, with capsular types-K15, K17, K50, K51, K52/wzi-50 and K2/wzi-2. Both phages showed short replication times, large burst sizes with rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both phages are genetically distinct phages from Myoviridae and Podoviridae family, with the lack of toxin, virulence, lysogeny and antibiotic resistance genes. These characteristics highlighted their promising potential for utilizing in phage therapy for combating XDR K. pneumoniae. Although phage cocktail combining vB_kpnM_05 and vB_kpnP_08 provided significant bacteriolysis for longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development of phage resistance under phages' selection pressures. Future study will be undertaken to elucidate the precise mechanisms by which these XDR K. pneumoniae developed phage resistance and their associated fitness cost. Remarkably, combining phage cocktail with amikacin at their sub-inhibitory concentrations produced potent synergy by completely suppressing bacterial regrowth in vitro. Our study demonstrated the significant therapeutic and prophylactic effectiveness of a phage cocktail-amikacin combination as a promising alternative strategy for overcoming bacteremia associated with XDR K. pneumoniae having carbapenemase and colistin resistance in vivo., Competing Interests: Declaration. Competing interests: The authors declare no competing interests. Informed consent: For this retrospective study of anonymous clinical isolates, the requirement for informed consent from patients was waived by the Institutional Review Board (IRB) of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (IRB No.2865/65)., (© 2024. The Author(s).)

Background: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients., Methods: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases., Results: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died., Conclusions: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus., Aim: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe., Methods: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls., Findings: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis., Conclusion: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess incidence rates of surgical site infections (SSI) by MRSA and to determine related factors and clinical outcome compared to MSSA, including country-specific, institutional and patient determinants., Patients and Methods: We performed a subgroup analysis of the Europe-wide SALT (NCT03353532) study population with MRSA SSI from 14 centres in France, Germany, Italy, Spain and the UK., Results: An overall MRSA SSI incidence of 0.06% ( n  = 104) was found in 178 903 patients undergoing invasive surgery in 2016. Frequently observed comorbidities were chronic cardiovascular disease, diabetes and solid tumours. Compared to the overall MRSA SSI incidence, incidence rates were significantly higher in Spain (58 of 67 934 cases) and lower in Germany (16 of 46 443 cases; both P  < 0.05). Centres with antibiotic stewardship (ABS) and infectious disease (ID) consultation programmes ( n  = 3/14) had lower MRSA rates (17 of 43 556 cases versus 61 of 83 048 cases, P  < 0.05). In bivariate analyses, MRSA SSI patients were significantly older, had higher BMI and more comorbidities compared to MSSA ( P  < 0.05 each). Surgery performed between 6:00 and 12:00 pm led to higher MRSA proportions among S. aureus SSI (17 of 104 cases versus 62 of 640 cases, P  < 0.05)., Conclusions: This study shows low overall and country-specific incidence rates of MRSA SSI in Europe. We could show significant differences between countries as well as between centres with established ABS and ID consultation programmes were observed. The number of those programmes seems too small against this background., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Antimicrobial stewardship (AMS) programmes are established across the world to treat infections efficiently, prioritize patient safety, and reduce the emergence of antimicrobial resistance. One of the core elements of AMS programmes is guidance to support and direct physicians in making efficient, safe and optimal decisions when prescribing antibiotics. To optimize and tailor AMS, we need a better understanding of prescribing physicians' experience with AMS guidance., Objectives: To explore the prescribing physicians' user experience, needs and targeted improvements of AMS guidance in hospital settings., Methods: Semi-structured interviews were conducted with 36 prescribing physicians/AMS guidance users from hospital settings in Canada, Germany, Israel, Latvia, Norway and Sweden as a part of the international PILGRIM trial. A socioecological model was applied as an overarching conceptual framework for the study., Results: Research participants were seeking more AMS guidance than is currently available to them. The most important aspects and targets for improvement of AMS guidance were: (i) quality of guidelines; (ii) availability of infectious diseases specialists; and (iii) suitability of AMS guidance to department context., Conclusions: Achieving prudent antibiotic use not only depends on individual and collective levels of commitment to follow AMS guidance but also on the quality, availability and suitability of the guidance itself. More substantial commitment from stakeholders is needed to allocate the required resources for delivering high-quality, available and relevant AMS guidance to make sure that the prescribers' AMS needs are met., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objective: To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe., Methods: This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case-control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching., Results: A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure., Conclusions: This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany. They identified critical shortcomings including the lack of clinical trials, a paucity of appropriate regulation and a shortage of phages for clinical use. Phage therapy is currently being applied to a limited number of patients as individual treatment trials. There is presently only one site in Germany for large-scale good-manufacturing-practice (GMP) phage production, and one clinic carrying out permission-free production of medicinal products. Several phage banks exist, but due to varying institutional policies, exchange among them is limited. The number of phage research projects has remarkably increased in recent years, some of which are part of structured networks. There is a demand for the expansion of production capacities with defined quality standards, a structured registry of all treated patients and clear therapeutic guidelines. Furthermore, the medical field is still poorly informed about phage therapy. The current status of non-approval, however, may also be regarded as advantageous, as insufficiently restricted use of phage therapy without adequate scientific evidence for effectiveness and safety must be prevented. In close coordination with the regulatory authorities, it seems sensible to first allow some centers to treat patients following the Belgian model. There is an urgent need for targeted networking and funding, particularly of translational research, to help advance the clinical application of phages.

Background: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors., Methods: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections., Results: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection., Conclusions: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors., Competing Interests: Potential conflicts of interest. C. M. C. reports the following grants or contracts unrelated to this work: Centers for Disease Control and Prevention (CDC) subaward from Johns Hopkins University to the Washington University in St. Louis (funding by the CDC grant number 1U54CK000617-01-00), vendor/individual agreement with Wayne State University for a case registry, and Associate Editor for Open Forum Infectious Diseases (1 May 2022 through 30 April 2023). D. F. P. reports payment or honoraria as a speaker for an antibiotic course for UMC Utrecht and as a teacher for Hospital Pharmacists in training for PAO; and participation on DSMB for the COBRA trial (Very short-course versus standard course antibiotic therapy in patients with acute Cholangitis after adequate endoscopic biliaRy drainage) in the Netherlands. M. J. M. reports consulting fees from Insmed and Biomerieux; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Microsoft Diagnostics (MSD), Insmed, and Teva; support for attending meetings and/or travel from MSD, Berlin Chemie; and participation on a Data Safety Monitoring Board or Advisory Board for Biomerieux, Insmed, MSD. J. T. S. reports payment or honoraria for manuscript writing for Gilead on subjects not related to this manuscript. M. B. reports support from Pfizer for attending a congress. N. K. reports royalties or licenses from Up To Date; consulting fees from Astellas, AstraZeneca, Biotest, ExeViR, Hansa, Merck Sharp and Dohme, Glasgow Smith Kline, Novartis Pharma, Takeda; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Astellas, Biotest, CSL Behring, Chiesi, Novartis Pharma, Sanofi, Sandoz, Takeda; and support for attending meetings and/or travel from Astellas, Novartis Pharma, Takeda. N. J. M. reports support for attending meetings and/or travel paid to author from Biotest; unpaid participation on a Data Safety Monitoring Board or Advisory Board for a CTX3 Study and paid participation on Advisory Boards for Takeda, MSD, and Pfizer. N. M. T. reports payment or honoraria for guest lecture for Boston Medical Center and Beth Israel Medical Center; payment for expert testimony for record review for Ficksman & Conley, LLP, in Boston, Massachusetts; participation on a Data Safety Monitoring Board or Advisory Board for United Network for Organ Sharing HIV Organ, Policy Equity (HOPE) Act Safety Review, and Workgroup (unpaid); role as Chair of the American Society of Transplantation and leadership or fiduciary role with Infectious Diseases Community of Practice (unpaid). O. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from MSD; and participation on a Data Safety Monitoring Board or Advisory Board for MSD. S. Be. reports grants or contracts unrelated to this work from Vancouver Costal Health Research Institute and Transplant Research Foundation of BC; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Merck; and participation on an Advisory Board for Evusheld (AstraZeneca). 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) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study describes the development and validation of structure indicators for clinical infectious disease (ID) care in German hospitals, which is important to adequately face the future challenges in ID medicine., Methods: A team of experts developed the structure indicators in a three-stage, multicriteria decision-making process: (1) identification of potential structure indicators based on a literature review, (2) written assessment process, and (3) face-to-face discussion to reach consensus and final selection of appropriate structure indicators. A field study was conducted to assess the developed structure indicators. A score based on the structure indicators was determined for each hospital and validated via receiver operator characteristic (ROC) curves using externally validated ID expertise (German Society of ID (DGI) Centre)., Results: Based on a list of 45 potential structure indicators, 18 suitable indicators were developed for clinical ID care structures in German hospitals. Out of these, ten key indicators were defined for the general and coronavirus disease 2019- (COVID-19-) specific clinical ID care structures. In the field survey of clinical ID care provision for COVID-19 patients in 40 German hospitals, the participating facilities achieved 0 to 9 points (median 4) in the determined score. The area under the ROC curve was 0.893 (95% CI: 0.797, 0.988; p < 0.001)., Discussion/conclusion: The structure indicators developed within the framework of a transparent and established development process can be used in the future to both capture the current state and future developments of ID care quality in Germany and enable comparisons., (Copyright © 2023. Published by Elsevier GmbH.)

The number of immunosuppressed patients continues to increase worldwide. The main reasons are the demographic development and improved long-term survival, also for patients under immunosuppression. A major cause of hospitalization and mortality among these patients are infections. Their management, including prevention and adequate treatment, plays a crucial role in survival and quality of life, but also with regard to economic factors.Infection management in immunocompromised patients faces new challenges today. Not only the increasing number, but also new groups of patients at risk and an increasingly aging and comorbid population pose problems for the treating physicians. While cancer medicine is no longer determined solely by radiotherapy and chemotherapy, new targeted substances are playing an increasingly important role. In addition, new targeted substances complicate adequate infection prophylaxis due to potential interactions. The worldwide increase in antibiotic-resistant pathogens complicates treatment of bacterial infections, which is associated with increased mortality, especially in the immunocompromised patient population. Further, the disruption of the microbiome shows negative antibiotic-associated effects. Hence the reasonable use of anti-infectives in prophylaxis and therapy is of great importance.There are many recommendations and guidelines for clinicians regarding the management of infections in immunocompromised patients. Overlaps of infectiology, hygiene as well as hematology and oncology sometimes lead to different recommendations. This article provides an overview of the currently existing evidence and guidelines for infection management in immunosuppressed patients., Competing Interests: Mellinghoff: Octapharma (Beratungtätigkeit), Gilead (Reisekosten und Fortbildung);Stemler: Bundesministerium für Bildung und Forschung – Forschungsgelder; Basilea Pharmaceuticals Inc. – Frschungsgelder Pfizer Inc. – Vortragshonorar; Deutsche Gesellschaft für Infektiologie (DGI e.V.) – Reisekosten; Meta-Alexander Foundation – ReisekostenClassen: Deutsches Zentrum für Infektionsforschung (Forschungsgelder und Reisekosten); Akademie für Infektionsmedizin (Dozentenhonorar); Ärtzekammer Nordhrein Westfalen (Dozentenhonorar); Gilead (Reisekosten und Fortbildung), (Thieme. All rights reserved.)

Purpose: Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary., Methods: 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account., Results: Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05)., Conclusion: In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients., (© 2021. The Author(s).)

Aims: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients., Methods and Results: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056)., Conclusions: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease., (© 2021. The Author(s).)

Patients with cancer are at increased risk of infection due to disease-associated or therapy-induced immunosuppression. Taking into account globally increasing antimicrobial resistance rates and negative effects associated with antibiotic treatments, the effective, appropriate and guideline-conform use of anti-infectives must be promoted in this clinical setting. The application of antibacterial prophylaxis should be limited to high-risk patients. Infection diagnostics and therapeutic strategies differ depending on the extent of expected immunosuppression and the patient's individual risk factors., (© The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2022.)

Background and Purpose: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry., Methods: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression., Results: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19., Conclusion: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: The Coronavirus Disease-2019 (COVID-19) pandemic has brought opportunities and challenges, especially for health services research based on routine data. In this article we will demonstrate this by presenting lessons learned from establishing the currently largest registry in Germany providing a detailed clinical dataset on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients: the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS)., Methods: LEOSS is based on a collaborative and integrative research approach with anonymous recruitment and collection of routine data and the early provision of data in an open science context. The only requirement for inclusion was a SARS-CoV-2 infection confirmed by virological diagnosis. Crucial strategies to successfully realize the project included the dynamic reallocation of available staff and technical resources, an early and direct involvement of data protection experts and the ethics committee as well as the decision for an iterative and dynamic process of improvement and further development., Results: Thanks to the commitment of numerous institutions, a transsectoral and transnational network of currently 133 actively recruiting sites with 7,227 documented cases could be established (status: 18.03.2021). Tools for data exploration on the project website, as well as the partially automated provision of datasets according to use cases with varying requirements, enabled us to utilize the data collected within a short period of time. Data use and access processes were carried out for 97 proposals assigned to 27 different research areas. So far, nine articles have been published in peer-reviewed international journals., Conclusion: As a collaborative effort of the whole network, LEOSS developed into a large collection of clinical data on COVID-19 in Germany. Even though in other international projects, much larger data sets could be analysed to investigate specific research questions through direct access to source systems, the uniformly maintained and technically verified documentation standard with many discipline-specific details resulted in a large valuable data set with unique characteristics. The lessons learned while establishing LEOSS during the current pandemic have already created important implications for the design of future registries and for pandemic preparedness and response., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Many haematology/oncology departments still provide a germ-free diet for neutropenic patients (neutropenic diet, ND) to minimise pathogen exposure, even though evidence on benefits is missing. We analysed the effects of a standard diet (SD) in neutropenic high-risk patients with cancer while focussing on infection-related outcomes., Patients and Methods: Based on the Cologne Cohort of Neutropenic Patients, we conducted a propensity score-matched case-control study in haematological/oncological patients with a period of neutropenia longer than five days treated at our department between January 2004 and December 2012 (implementation of SD in January 2008). We assessed the association between an SD and selected infection-related end-points in an adjusted multivariable regression model and time-to-event analysis., Results: In total, 2086 neutropenic episodes (1043 per diet group) were included into analysis. The median days of neutropenia were 9 (interquartile range 7-16). The adjusted multivariable model revealed no association between the SD and severity and persistence of fever, death within 28 days, antibiotic treatment and weight loss >3 kg and a non-significant adjusted association between SD and duration of antibiotic treatment and blood stream infections. There was a significant association between SD and incidence of diarrhoea (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.45-0.68; P < 0.001), nausea (OR, 0.53; 95% CI, 0.43-0.66; P < 0.001) and weight loss >1 kg (OR, 0.93; 95% CI, 0.89-0.98; P = 0.002) with fewer events in SD than in the ND group. The hazard ratios of SD for the analysed end-points were non-significant., Conclusion: In our study, the implementation of an SD for high-risk neutropenic patients with cancer was safe regarding infection-related end-points., Competing Interests: Conflict of interest statement 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 paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Antibiotic consumption increases worldwide steadily. Turkey is now top on the list of global consumption and became a prototype of excessive use of antibiotics. In the last two decades, family physicians (FPs) have become key figures in the healthcare system. This study aims to understand the reasons for inappropriate antibiotic prescribing and elicit suggestions for improving antibiotic use in primary care from doctors themselves., Methodology: This is a qualitative semi-structured interview study with research dialogues guided by the Vancouver School of interpretive phenomenology. Fourteen FPs from different parts of Turkey were questioned on inappropriate antibiotic prescriptions and their suggestions for improving antibiotic use., Results: The most important reasons for prescribing antibiotics without acceptable indications were patient expectations, defensive medical decision making, constraints due to workload, and limited access to laboratories. The most remarkable inference was the personal feeling of an insecure job environment of the FPs. The most potent suggestions for improving the quality of antibiotic prescription were public campaigns, improvements in the diagnostic infrastructures of primary care centers, and enhancing the social status of FPs. The FPs expressed strong concerns related to the complaints that patients make to administrative bodies., Conclusions: Primary care physicians work under immense pressure, stemming mainly from workload, patient expectations, and obstacles related to diagnostic processes. Improving the social status of physicians, increasing public awareness, and the facilitation of diagnostic procedures was the methods suggested for increasing antibiotic prescription accuracy., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Salih Hosoglu, Annika Yanina Classen, Zekeriya Akturk.)

Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.

Introduction: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk., Patients and Methods: We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality., Results: In total, 435 cancer patients were included in our analysis. Commonest age category was 76-85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable., Conclusion: Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

Objectives: Novel formulations (gastro-resistant tablet and intravenous solution) of posaconazole (POS) have been approved in prophylaxis and therapy of invasive fungal diseases (IFDs). Study aim was to analyze treatment strategies and clinical effectiveness., Methods: We set up a web-based registry on www.ClinicalSurveys.net for documentation of comprehensive data of patients who received novel POS formulations. Data analysis was split into two groups of patients who received novel POS formulations for antifungal prophylaxis (posaconazole prophylaxis group) and antifungal therapy (posaconazole therapy group), respectively., Results: Overall, 180 patients (151 in the posaconazole prophylaxis group and 29 in the posaconazole therapy group) from six German tertiary care centers and hospitalized between 05/2014 - 03/2016 were observed. Median age was 58 years (range: 19 - 77 years) and the most common risk factor for IFD was chemotherapy (n = 136; 76%). In the posaconazole prophylaxis group and posaconazole therapy group, median POS serum levels at steady-state were 1,068 μg/L (IQR 573-1,498 μg/L) and 904 μg/L (IQR 728-1,550 μg/L), respectively (P = 0.776). During antifungal prophylaxis with POS, nine (6%) probable/proven fungal breakthroughs were reported and overall survival rate of hospitalization was 86%. The median overall duration of POS therapy was 18 days (IQR: 7 - 23 days). Fourteen patients (48%) had progressive IFD under POS therapy, of these five patients (36%) died related to or likely related to IFD., Conclusions: Our study demonstrates clinical effectiveness of antifungal prophylaxis with novel POS formulations. In patients treated for possible/probable/proven IFD, we observed considerable mortality in patients receiving salvage treatment and with infections due to rare fungal species., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Digital Medicine has become an integral part of clinical infectious diseases. For chronic infections such as HIV and Hepatitis C, treatment with software tools for resistance phenotyping has become standard of care. Computer-assisted decision aids as well as electronic health records are currently being implemented on a regional basis in Germany. They assist physicians in avoiding treatment errors and selecting antibiotics rationally.Mobile devices allow documentation of the course of chronic infections and improve communication between patient and physician. This offers new opportunities in areas with underdeveloped health infrastructure. In the future, it will become possible to integrate complex datasets, such as genome and microbiome, into clinical treatment decisions. This would adjust treatment individually based on host immune response, metabolism, and microbiota colonization., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)