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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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: According to self-reported frequencies, every fifth or sixth dwelling in Germany is affected by dampness and/or mold. This carries a potential risk to health. Methods: This review is based on pertinent publications retrieved by a selective literature search and inquiry in the GENESIS database, on the AWMF guideline on the medical clinical diagnosis of indoor mold exposure, as updated in 2023, and on the relevant contents of other current guidelines. Based on this research, we present an algorithm for the evaluation of health problems that may be due to mold in indoor environments. Results: A rational diagnostic work-up begins with history-taking and physical examination, with attention to risk factors--above all, immune compromise and atopy. If there is evidence of atopy, targeted allergy diagnostics should be performed, consisting of a skin prick test and/or measurement of specific IgE antibodies, supplemented whenever indicated by provocative testing and cellular test systems. If the patient's immune response is compromised, the immediate cessation of mold exposure has absolute priority. Any suspected invasive fungal infection should be evaluated with radiological, microbiological, serological, and immunological testing. Indoor measurements of mold fungi, microbial volatile organic compounds (MVOC), and/or mycotoxins are generally not indicated as part of the medical evaluation; nor are blood or urine tests for particular mold components or metabolites. Conclusion: Mold in indoor environments should be dealt with by rapid exposure elimination for patients at risk, the rational diagnostic evaluation of any symptoms and signs of disease, and patient education about the possibilities and limitations of diagnostic testing and the generally limited utility of measurements in the affected interior spaces. [ABSTRACT FROM AUTHOR]

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.)

Introduction: Our monocentric and retrospective study aimed to investigate the clinical effectivity of HEPA filters in combination with the antifungal drug prophylaxis in patients with AML undergoing intensive chemotherapy and allogeneic stem cell transplantation (SCT)., Methods/results: We included 177 patients between 2005 and 2015 representing a total of 372 in-hospital stays, 179 in the HEPA cohort (+HEPA) and 193 in the cohort without HEPA filters (-HEPA). No significant additional benefit of HEPA filtration on the risk reduction of IFI was observed. HEPA filtration did not significantly affect the risk of intensive care unit (ICU) admissions or early mortality rates. In patients who received allogeneic SCT in first complete remission with antifungal drug prophylaxis during prior induction treatment, a numerical but not significant improvement in long-term overall survival was noted in the +HEPA cohort compared to the -HEPA cohort (55% to 66%, p = 0.396). For better depicting of the clinical reality, we determined the so-called clinical suspected IFI (csIFI) -defined as cases with antifungal treatment after recommended prophylaxis without fulfilling current EORTC criteria. Especially in patients with a high risk for second IFI, significant risk reduction of csIFI and frequency of ICU admissions was observed when voriconazole was used as secondary antifungal prophylaxis. (csIFI, adjusted effect: OR 0.41, 95% CI (0.21 - 0.82), p = 0.01; csIFI, subgroup-specific effect: OR 0.35, 95% CI (0.15 - 0.78), p = 0.01; ICU, adjusted effect: OR 0.44, 95 CI (0.19 - 1.01), p = 0.05; respectively)., Discussion: In summary, the study suggests the efficacy of secondary antifungal prophylaxis in preventing IFI in AML patients undergoing intensive treatment. The addition of HEPA filtration also demonstrated additional numerous benefits in reducing the frequency of IFI-associated complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Preyer, Vettorazzi, Fiedler, Rohde, Stemler, Gönner, Bokemeyer, Khandanpour, Wortmann and Kebenko.)

This article is an abridged version of the updated AWMF mould guideline "Medical clinical diagnostics in case of indoor mould exposure - Update 2023", presented in July 2023 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin, GHUP), in collaboration with German and Austrian scientific medical societies, and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. There is no evidence for a causal relationship between moisture/mould damage and human diseases, mainly because of the ubiquitous presence of fungi and hitherto inadequate diagnostic methods. Sufficient evidence for an association between moisture/mould damage and the following health effects has been established for: allergic respiratory diseases, allergic rhinitis, allergic rhino-conjunctivitis, allergic bronchopulmonary aspergillosis (ABPA), other allergic bronchopulmonary mycosis (ABPM), aspergilloma, Aspergillus bronchitis, asthma (manifestation, progression, exacerbation), bronchitis (acute, chronic), community-acquired Aspergillus pneumonia, hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EEA)), invasive Aspergillosis, mycoses, organic dust toxic syndrome (ODTS) [workplace exposure], promotion of respiratory infections, pulmonary aspergillosis (subacute, chronic), and rhinosinusitis (acute, chronically invasive, or granulomatous, allergic). In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitization prevalence of 3-22,5 % in the general population across Europe. Limited or suspected evidence for an association exist with respect to atopic eczema (atopic dermatitis, neurodermatitis; manifestation), chronic obstructive pulmonary disease (COPD), mood disorders, mucous membrane irritation (MMI), odor effects, and sarcoidosis. (iv) Inadequate or insufficient evidence for an association exist for acute idiopathic pulmonary hemorrhage in infants, airborne transmitted mycotoxicosis, arthritis, autoimmune diseases, cancer, chronic fatigue syndrome (CFS), endocrinopathies, gastrointestinal effects, multiple chemical sensitivity (MCS), multiple sclerosis, neuropsychological effects, neurotoxic effects, renal effects, reproductive disorders, rheumatism, sick building syndrome (SBS), sudden infant death syndrome, teratogenicity, thyroid diseases, and urticaria.The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 ( Aspergillus fumigatus , A. flavus ) of the German Biological Agents Act (Biostoffverordnung). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, water activity, temperature and above all the growth substrates.In case of indoor moisture/mould damage, everyone can be affected by odor effects and/or mood disorders.However, this is not an acute health hazard. Predisposing factors for odor effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly regarding infection risk are immunocompromised persons according to the classification of the German Commission for Hospital Hygiene and Infection Prevention (Kommission für Krankenhaushygiene und Infektionsprävention, KRINKO) at the Robert Koch-Institute (RKI), persons suffering from severe influenza, persons suffering from severe COVID-19, and persons with cystic fibrosis (mucoviscidosis); with regard to allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma must be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections, the reader is referred to the specific guidelines. Regarding mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medical point of view, it is important that indoor mould infestation in relevant magnitudes cannot be tolerated for precautionary reasons.For evaluation of mould damage in the indoor environment and appropriate remedial procedures, the reader is referred to the mould guideline issued by the German Federal Environment Agency (Umweltbundesamt, UBA)., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 161/001., (Thieme. All rights reserved.)

Introduction: A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection., Methods: Adults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti-SARS-CoV-2 receptor-binding domain (RBD) and spike-subunit-1 and spike-subunit-2 antibodies were measured. A sub-study assessed SARS-CoV-2-specific plasma and memory B-cell and memory T-cell responses in peripheral blood mononuclear cells by enzyme-linked immunospot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan-Meier survival analysis, and Cox proportional hazard ratios., Results: Of the 132 participants, 47 (36%) reported incident SARS-CoV-2 infection at a median 16.5 (16.25-21) weeks after the third-dose vaccination. RBD titres and B-cell responses, but not T-cell responses, increased after the third-dose vaccine. Whereas no significant difference in day 14 antibody titres or T-cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B-cell frequencies were significantly higher in those who did not develop infection [10.0% (4.5%-16.0%) versus 4.9% (1.6%-9.3%), p = 0.01]. RBD titres and memory B-cell frequencies remained significantly higher at 10 months than day 0 levels (p < 0.01)., Discussion: Robust antibody and B-cell responses persisted at 10 months following the third-dose vaccination. Higher memory B-cell frequencies, rather than antibody titres or T-cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection., Competing Interests: JS has received research support by the German Ministry of Education and Research BMBF, Basilea Pharmaceuticals, Noscendo; has received speaker honoraria by AbbVie, Gilead, Hikma and Pfizer; has been a consultant to Gilead, Alvea Vax. and Micron Research 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, infill healthcare communication GmbH, 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, Jazz Pharmaceuticals Germany GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH, University Hospital and LMU Munich and VITIS GmbH; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A filed patent 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. SS has received financial support by Gilead Sciences, ViiV Healthcare, and MSD for attendance to international conferences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Byrne, Gu, Garcia-Leon, Gaillard, Saini, Alalwan, Tomás-Cortázar, Kenny, Donohue, Reynolds, O’Gorman, Landay, Doran, Stemler, Koehler, Cox, Olesen, Lelievre, O’Broin, Savinelli, Feeney, O’Halloran, Cotter, Horgan, Kelly, Sadlier, de Barra, Cornely, Gautier, Mallon and All Ireland Infectious Diseases cohort study and VACCELERATE consortium.)

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.)

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.)

Purpose: Considering the re-emergence of poliomyelitis (PM) in non-endemic regions, it becomes apparent that vaccine preventable diseases can rapidly develop epi- or even pandemic potential. Evaluation of the current vaccination status is required to inform patients, health care providers and policy makers about vaccination gaps., Methods: Between October 28 2022 and November 23 2022, 5,989 adults from the VACCELEREATE Volunteer Registry completed an electronic case report form on their previous PM vaccine doses including number, types/-valencies and the time of administration based on their vaccination records. A uni-/multivariable regression analysis was performed to assess associations in participant characteristics and immunization status., Results: Among German volunteers (n = 5,449), complete PM immunization schedule was found in 1,981 (36%) participants. Uncertain immunization, due to unknown previous PM vaccination (n = 313, 6%), number of doses (n = 497, 9%), types/-valencies (n = 1,233, 23%) or incoherent immunization schedule (n = 149, 3%) was found in 40% (n = 2,192). Out of 1,276 (23%) participants who reported an incomplete immunization schedule, 62 (1%) never received any PM vaccine. A total of 5,074 (93%) volunteers reported having been vaccinated at least once and 2,087 (38%) indicated that they received vaccination within the last ten years. Female sex, younger age, as well as availability of first vaccination record were characteristics significantly associated with complete immunization (p < 0.001)., Conclusion: Full PM immunization schedule was low and status frequently classified as uncertain due to lack of details on administered doses. There is an obviousneed for improved recording to enable long-term access to detailed vaccination history in the absence of a centralized immunization register., (© 2024. The Author(s).)

Invasive fungal diseases (IFD) are difficult to treat and pose a significant threat to immunocompromised individuals. Current antifungal agents face limitations, including antifungal resistance and adverse effects. This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy. For prophylactic purpose in high-risk populations to develop IFD, monoclonal antibodies against different virulence factors of Candida spp. have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their clinical value is still discussed.In summary, major advances to treat IFD have been observed, but challenges for their establishment in the clinical routine persist., Competing Interests: SCM berichtet Fördermittel von der Universität zu Köln, vom DZIF und von der DGIM sowie Vortragshonorar von Pfizer. OAC berichtet Fördermittel oder Verträge von BMBF, Cidara, DZIF, EU-DG RTD, F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Beratungshonorare von Abbvie, AiCuris, Basilea, Biocon, Cidara, Seqirus, Gilead, GSK, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Mundipharma, Noxxon, Octapharma, Pardes, Partner Therapeutics, Pfizer, PSI, Scynexis, Seres, Shionogi, The Prime Meridian Group; Vortragshonorare von Abbott, Abbvie, Akademie für Infektionsmedizin, Al-Jazeera Pharmaceuticals/Hikma, amedes, AstraZeneca, Deutscher Ärzteverlag, Gilead, GSK, Grupo Biotoscana/United Medical/Knight, Ipsen Pharma, Medscape/WebMD, MedUpdate, MSD, Moderna, Mundipharma, Noscendo, Paul-Martini-Stiftung, Pfizer, Sandoz, Seqirus, Shionogi, streamedup!, Touch Independent, Vitis; Vergütung für Sachverständigengutachten von Cidara; Teilnahme an einem Gremium zur Überwachung der Datensicherheit oder einem Beratungsgremium für Boston Strategic Partners, Cidara, IQVIA, Janssen, MedPace, PSI, Pulmocide, Vedanta Biosciences JS has received research support by the Ministry of Education and Research (BMBF), the Medical Faculty of the University of Cologne, Noscendo and Basilea Pharmaceuticals; has received speaker honoraria by AbbVie, Gilead, Hikma, Pfizer; has been a consultant to Gilead, Produkt&Markt GmbH, Alvea Vax. and Micron Research; all outside the submitted work. RS erhielt Forschungsförderung vom Deutschen Zentrum für Infektionsforschung e.V. (DZIF Clinical Leave) und dem Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen (FF-Med), Vortragshonorare von der Akademie für Infektionsmedizin e.V., Hikma und Pfizer sowie Reiseunterstützung von der European Confederation of Medical Mycology, Page Medical und Pfizer außerhalb der eingereichten Arbeit., (Thieme. All rights reserved.)

Objectives: Midostaurin is an oral multitargeted tyrosine kinase inhibitor for the treatment of acute myeloid leukemia (AML). Therapeutic drug monitoring of midostaurin may support its safe use when suspecting toxicity or combined with strong CYP3A4 inhibitors., Methods: A stable isotope dilution liquid chromatography-tandem mass spectrometry method was developed and validated for the determination and quantification of midostaurin in human plasma and serum. Midostaurin serum concentrations were analyzed in 12 patients with FMS-like tyrosine kinase 3 (FLT3)-mutated AML during induction chemotherapy with cytarabine, daunorubicin, and midostaurin. Posaconazole was used as prophylaxis of invasive fungal infections., Results: Linear quantification of midostaurin was demonstrated across a concentration range of 0.01-8.00 mg/L. Inter- and intraday imprecisions of the proposed method were well within ±10%. Venous blood samples were taken in nine and three patients in the first and second cycle of induction chemotherapy. Median (range) midostaurin serum concentration was 7.9 mg/L (1.5-26.1 mg/L) as determined in 37 independent serum specimens., Conclusion: In a real-life cohort of AML patients, interindividual variability in midostaurin serum concentrations was high, highlighting issues concerning optimal drug dosing in AML patients. A personalized dosage approach may maximize the safety of midostaurin. Prospective studies and standardization of analytical methods to support such an approach are needed., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Purpose: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect., Methods: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 10 6 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 10 6 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed., Results: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 10 6 copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment., Conclusion: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients., (© 2023. The Author(s).)

Introduction: In Germany, the growing incidence of invasive fungal infections (IFIs) is a significant health concern, particularly impacting individuals with compromised immune systems due to factors like increasing transplant recipients, an ageing population, and heightened use of immunosuppressive medications. Diagnosing IFI remains challenging, and the integration of biomarker assays into clinical practice is difficult. Antifungal resistance, exemplified by pan-antifungal-resistant Candida auris cases, adds complexity to treatment. This study aims to provide a concise overview of the diagnostic and treatment landscape for IFI in Germany, identifying areas for improvement and paving the way for targeted interventions., Methods: Data were collected using an online electronic case report form from October 2021 to February 2023. The survey included questions about institutional practices related to fungal infection diagnosis and treatment, with invitations extended to researchers nationwide., Results: The study surveyed 58 hospitals across Germany. Notably, 77.6% managed high-risk patients for IFI. While 86% had onsite microbiology labs, a significant difference was noted for high-risk patients (93% in specialized hospitals versus 62% in others). Microscopy services had 96% coverage, while overall access to culture was 96%. Antigen tests had 96% coverage, and antibody access was reported at 98%. PCR testing was available at 98%. Imaging access showed no significant access differences. Variability existed in amphotericin B formulations based on patient profiles. Therapeutic drug monitoring was more common in high-risk patient institutions (89.5% versus 50.0%). All analysed institutions reported access to surgery (100%)., Conclusions: Addressing identified disparities in diagnostic and therapeutic resources for IFI is crucial to improving patient outcomes. The study calls for ongoing research and collaboration to optimize strategies for the prevention and treatment of IFI, emphasizing the importance of equitable access to resources, especially in high-risk patient populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

None., Competing Interests: See Table 14. Figure 1Incubation period [775, 778].Figure 2Temporal relationship between sensitization and first allergic reaction [775, 778].Figure 3Latency period [775, 778]. Figure 4Annual course of the occurrence of mold spores in the outdoor air, spore concentrations as weekly values in spores/m3 air, pollen trap in Leverkusen. Source: Mülleneisen 2023, unpublished data. A volumetric spore trap based on the Hirst principle was used to determine the concentration [269] with associated microscopic analysis of the samples. The measurement method is standardized [738].Figure 5Monthly course of spore concentrations (in spores/m3 of air) in the outdoor air for several mold genera as an example for one year and one measuring station in Germany: a) Pleospora 2021 – Berlin measuring station, b) Cladosporium 2021 – Chemnitz measuring station, c) Alternaria 2021 – Berlin measuring station, d) Epicoccum 2021 – Berlin measuring station. Missing data at the Chemnitz station in the periods: February 24, 2021 to March 1, 2021 and April 1, 2021 to April 6, 2021. The figure was provided by the German Pollen Information Service Foundation (Stiftung Deutscher Polleninformationsdienst). The concentration was determined using volumetric spore traps based on the Hirst principle [269] followed by microscopic analysis of the samples. The measurement procedure is standardized [738].Risk matrix 1. Risk of infection by mold (The darker a box, the greater the possible health risk.). Risk matrix 2.Risk of sensitization/risk of allergy caused by mold (the darker the color, the greater the possible health risk). *Proof of the clinical relevance of a sensitization determined in the allergy test required! Table 2.Important sources of frequently occurring mold species and genera (examples from practical investigations). Species or genusImportant sourcesCladosporium herbarum, Alternaria alternata, Botrytis cinereaVegetation, outdoor air-associatedAspergillus versicolor complex and Scopulariopsis brevicaulisDamp plasterXerophilic Aspergillus species of the Restrictus complex (esp. A. penicillioides and A. restrictus) as well as Aspergillus glaucus/pseudoglaucus and A. montevidensis, Wallemia sebiCellulose-containing materials with only slightly increased moistureAspergillus fumigatusComposting, rotting of plant material, indicator for thermotolerant processesChaetomium spp., Trichoderma spp., Phialophora spp.Colonizer of damp wood and cellulose materials such as cardboardPenicillium speciesPerishable food, waste, organic waste and wallpaper, house dustSarocladium strictum, Parengyodontium album, Lecanicillium psalliotae and Simplicillium spp.Polystyrene floor insulation with prolonged moisture penetrationStachybotrys chartarum, Acremonium spp, Chaetomium spp.Very moist, cellulose-containing building materialsWallemia sebi, Aspergillus restrictus complexKeeping caged animals with bedding Table 3.Examples of species complexes based on molecular analyses (modified according to [297]). Complex or groupSelected speciesMolecular markers for differentiationAspergillus versicolor complexA. versicolor, A. amoenus, A. creber, A. jensenii, A. protuberus, et al.CaM, β-TubAspergillus niger complexA. niger, A. acidus, A. aculeatus, A. brasiliensis, A. tubingensis, et al.CaM, β-TubAspergillus fumigatus complexA. fumigatus, A. lentulus, A. novofumigatus, A. fumigatiaffinis, et al.CaM, β-Tub (Note: Cultivation at 37 °C; Differentiation A. lentulus)Fusarium solani complexF. solani, F. keratoplasticum, F. petroliphilum, F. lichenicola, et al.EF-1α, RPB-1 and/or RPB-2 Table 4.Evidence for the relationship between indoor moisture/mold exposure and disease (in alphabetical order), modified from [7, 39, 45, 58, 59, 74, 78, 79, 80, 101, 108,111, 116, 119, 131, 133, 162, 169, 175, 181, 182, 183, 201, 202, 204, 211, 212, 245, 263, 273, 275, 287, 289, 291, 298, 303, 316, 319, 322, 338, 363, 370, 394, 437, 442, 444, 445, 449, 450, 451, 462, 465, 466, 467, 490, 499, 501, 504, 509, 514, 520, 521, 522, 525, 526, 528, 532, 534, 537, 540, 546, 547, 552, 553, 568, 569, 596, 598, 632, 635, 642, 643, 644, 645, 652, 655, 694, 698, 717, 722, 742, 746, 754, 756, 757, 777, 783, 790, 791, 794, 797]. Causal relationship Sufficient evidence for an association1Allergic bronchopulmonary aspergillosis (ABPA) Allergic bronchopulmonary mycoses (ABPM) Allergic respiratory diseases Allergic rhinitis Allergic rhinoconjunctivitis Aspergilloma Aspergillosis Aspergillus bronchitis Asthma (manifestation, progression, exacerbation) Bronchitis (acute, chronic) Community-acquired aspergillus pneumonia Favoring respiratory infections Hypersensitivity pneumonitis (HP); extrinsic allergic alveolitis (EAA) Invasive aspergillosis Mycoses Organic dust toxic syndrome (ODTS) (workplace) Pulmonary aspergillosis (subacute, chronic) Rhinosinusitis (acute, chronic invasive or granulomatous, allergic)Limited or suspected evidence of an associationAtopic eczema / atopic dermatitis / neurodermatitis (manifestation) Chronic obstructive pulmonary disease (COPD) Mood disorders Mucous membrane irritation (MMI) Odor effects SarcoidosisInadequate or insufficient evidence for an associationAcute idiopathic pulmonary hemorrhage in children Airborne mycotoxicosis Arthritis Autoimmune diseases Cancer Chronic fatigue syndrome (CFS) Endocrinopathies Gastrointestinal effects Multiple Chemical Sensitivity (MCS) Multiple sclerosis Neuropsychological effects Neurotoxic effects Sudden infant death syndrome Renal effects Reproductive disorders Rheumatism Sick building syndrome (SBS) Teratogenicity Thyroid diseases Urticaria 1The diseases listed here can be subsumed under the term Building Related Illness (BRI), even though BRI requires that the etiology, pathology, pathophysiology, diagnosis, treatment, prevention and prognosis are clearly known [429, 663]. Table 5.Examples of typical antigens and antigen sources for hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EAA) (mod. after Costabel et al. 2020 [113]). AntigenAntigen sourceHP typeBacteria   Thermophilic actinomycetesMoldy hay and straw Farmer’s lungSugar cane dustBagassosis   Klebsiella oxytocaHumidifierHumidifier lung Mycobacteria   Mycobacterium avium complexWhirlpoolsWhirlpool lung (hot tub lung)   Mycobacterium immunogenumCooling lubricantsMachinist’s lungMushrooms   Absidia corymbiferaMoldy hay and straw Farmer’s lung   Trichosporon cutaneumInteriorsSummer-type alveolitis   Penicillium roquefortiCheese production/industrial sourcesCheese washer lung    Purpureocillium lilacinum, Aspergillus spp. Wind instrumentsWind instrument alveolitisAnimal proteins   Feathers and excrementBirdsBird keeper lung   Serum and urineRatsRat protein alveolitisPlant proteins   Nut dustTiger nutsTigernut alveolitis   Soy dustSoy productsSoy dust alveolitis   Wood dustVarious wood dustsWoodworker’s alveolitisEnzymes   PhytaseAnimal feed productionPhytase alveolitis   Enzymes from Bacillus subtilisBiological cleaning agentDetergent lung Table 6.Diagnostic criteria for allergic bronchopulmonary aspergillosis. a) Diagnostic criteria for allergic bronchopulmonary aspergillosis according to Rosenberg et al. [586]:Main criteria:   1. Bronchial asthma    2. Positive immediate reaction in the skin test for Aspergillus fumigatus   3. Total IgE > 417 IU/mL   4. Positive specific IgE against Aspergillus fumigatus   5. IgG antibodies against Aspergillus fumigatus   6. Blood eosinophilia (> 1,000 Eos/µL)   7. Central bronchiectasis   8. Radiological volatile or permanent pulmonary infiltratesSecondary criteria   Tough mucus plugs   Positive sputum culture for Aspergillus fumigatus   Late reaction in the intradermal test for Aspergillus fumigatusb) Modified ISHAM diagnostic criteria for allergic bronchopulmonary aspergillosis 2021 [616]:Combination of criteria with best sensitivity/specificity:   1. Bronchial asthma   2. Aspergillus fumigatus-specific IgE > 0.35 kU/L   3. Total IgE > 500 IU/mLand at least two of the following criteria:   1. Aspergillus fumigatus-specific IgG > 27 mgA/dL   2. Bronchiectasis in CT thorax   3. Eosinophilia in the blood count > 500/µL Table 7.Mold mycoses and their pathogens [712]. Infectious disease (invasive mycosis)Pathogen (risk group according. TRBA 460 (2016) [712]AspergillosisA. fumigatus (2)A. flavus (2)A. niger (complex) (1, 2)A. terreus (2)A. nidulans (1)MucormycosisRhizopus oryzae (2)Mucor sp. (1)Rhizomucor (1)PhaeohyphomycosesCurvularia sp. (1)Bipolaris sp. (1)Alternaria sp. (1)HyalohyphomycosesFusarium sp. (1, 2)Pseudallescheria sp.= Scedosporium sp. (2)PenicilliosesTalaromyces (formerly Penicillium) marneffei (2) Table 8.Differential diagnosis of extrinsic allergic alveolitis (EAA) and organic dust toxic syndrome (ODTS) [354]. FeaturesEAAODTSExposureVarious allergensEndotoxins, high exposureIncidence2 – 30 / 10,00010 – 100 / 10,000Latency4 – 8 hours4 – 12 hoursAuscultationEnd-expiratory rales on both sides basalNormal, possibly rattling noisesLung functionRestriction (rarely obstruction, DLCO reducedNormal (possible restriction)PrecipitinsOften specific IgGMostly negative Table 9.Immunosuppression risk groups of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute [349]. Risk group 1 (moderate immunosuppression/deficiency)– Granulocytopenia < 0.5 × 109 /L; (< 500/µL) probably up to 10 days (analogous to leukopenia < 1 × 109 /L; < 1,000/µL), – Autologous stem cell transplantation up to 3 months after day 0 (day of stem cell return) – Lack of CD4-positive T helper cells < 200/µL (Caveat: age-appropriate normal values in children) – Autologous stem cell transplantation up to 3 months after intensive therapy phase Patients who have more than one characteristic of the immunosuppression/deficiency listed under risk group 1 are assigned to risk group 2.Risk group 2 (severe immunosuppression/deficiency)– Granulocytopenia < 0.5 × 109 /L (< 500/μL) for more than 10 days (analogous to leukopenia < 1× 109 /L; < 1,000/μL) – Severe aplastic anemia or macrophage activation syndrome during intensive immunosuppressive therapy – Allogeneic bone marrow or stem cell transplantation up to 6 months after completion of the intensive therapy phase (important: extent of GVHD and ongoing iatrogenic immunosuppression) – Acute inpatient treatment phase for autologous stem cell transplantation or after solid organ transplantation (until discharge)Risk group 3 (very severe immunosuppression/deficiency)– Allogeneic BMT/PBSCT in intensive therapy phase (until engraftment = regeneration of granulopoiesis) – Severe GVHD grade III or IV under intensive immunosuppression The decision to assign patients after allogeneic stem cell transplantation to group 3 is ultimately made by the treating hematologist-oncologist after reviewing all findings.GVHD = graft-versus-host-disease = graft-versus-host-reaction; BMT = mone marrow transplantation; PBSCT = peripheral blood stem cell transplantation. Table 1.Medline search on the topic of the guideline (as of 12-2014 and 6-2022). KeywordsNumber of publications found Status 12-2014 [777]Number of publications found Status 6-2022Indoor mo(u)ld or indoor dampness and human health1,9493,145Indoor mo(u)ld or indoor dampness and human health and allergy1,8753,126Indoor mo(u)ld asthma440805Indoor mo(u)ld health asthma285564Indoor mo(u)ld human health asthma494Indoor mo(u)ld allergy1,198Indoor mo(u)ld health allergy434774Indoor mo(u)ld human health allergy689Indoor mo(u)ld atopy89Indoor mo(u)ld health atopy2459Indoor mo(u)ld human health atopy55Indoor mo(u)ld arthritis8Indoor mo(u)ld health arthritis4Indoor mo(u)ld human health arthritis3Indoor mo(u)ld rheumatism5Indoor mo(u)ld health rheumatism4Indoor mo(u)ld human health rheumatism3Mo(u)ld arthritis rheumatism4662Indoor mo(u)ld arthritis rheumatism2Indoor mo(u)ld health arthritis rheumatism2Indoor mo(u)ld human health arthritis rheumatism1Indoor mo(u)ld infection750Indoor mo(u)ld health infection74435Indoor mo(u)ld human health infection357Indoor mo(u)ld irritation113Indoor mo(u)ld health irritation4295Indoor mo(u)ld human health irritation85Indoor mo(u)ld symptoms1,159Indoor mo(u)ld health symptoms449724Indoor mo(u)ld human health symptoms594Indoor mo(u)ld ergosterol50Indoor mo(u)ld health ergosterol2436Indoor mo(u)ld human health ergosterol27Indoor mo(u)ld review450Indoor mo(u)ld health review301Indoor mo(u)ld human health review160266Indoor mo(u)ld trial67Indoor mo(u)ld health trial40Indoor mo(u)ld human health trial1732Indoor mo(u)ld clinical diagnosis89194Indoor mo(u)ld health clinical diagnosis113Indoor mo(u)ld human health clinical diagnosis93Indoor mo(u)ld diagnostic / diagnostics800Indoor mo(u)ld health diagnostic / diagnostics273449Indoor mo(u)ld human health diagnostic / diagnostics353Indoor mo(u)ld prevention654Indoor mo(u)ld health prevention216433Indoor mo(u)ld human health prevention358Indoor mo(u)ld treatment650Indoor mo(u)ld health treatment229360Indoor mo(u)ld human health treatment293Indoor mo(u)ld therapy507Indoor mo(u)ld health therapy196291Indoor mo(u)ld human health therapy250Indoor mo(u)ld air filter174Indoor mo(u)ld health air filter5494Indoor mo(u)ld human health air filter55 Table 10.Stage I - IV after conjunctival provocation test (CPT) [235]. Stage IForeign body sensation, reddening of the conjunctiva, onset of itchingStage IIAs I, plus lacrimation, more intense itching, reddening of the conjunctiva tarsi of the lower eyelidStage IIIAs II, additionally reddening of the conjunctiva tarsi of the upper eyelid, severe itching, blepharospasmStage IVAs III, additionally chemosis, eyelid swelling, irresistible itching Table 11.Selection of diagnostic methods without sufficient scientific evidence or without a medical or scientific basis in environmental medicine [5, 73, 232, 283, 350, 351, 352, 353, 355, 357, 512, 535, 684]. Diagnostic methods without sufficient scientific evidenceStress tests in body mediae.g., molds in the bloodAllergological examinationse.g., serial dilution titration, cytotoxic blood tests, determination of IgG and IgA antibodies directed against molds in type I allergiesInvestigations into disorders of the immune systeme.g., lymphocyte stimulation test, determination of lymphocyte subpopulations, determination of cytokinesInvestigations of the oxidative systeme.g., determination of oxidative stressOphthalmological examinationse.g., visual contrast sensitivity Test (VCS test)Diagnostic methods without a medical or scientific basisHolistic or bioenergetic diagnostic procedurese.g., electro-acupuncture according to Voll, bioresonance procedures, pendulum, Vega test, decoder dermography, biotonometry, biotensor, Kirlian photography (plasma print procedure, energetic terminal point diagnosis), regulation thermography according to Rost, auriculodiagnostics, kinesiology, aurascopy, iris diagnostics“Clinical ecology” proceduree.g., cytotoxic blood tests, provocation and neutralization test (PN test) Table 12.Examples of treatment methods without sufficient scientific evidence or without a medical or scientific basis in environmental medicine [5, 73, 160, 384, 512, 762]. Treatment methods without sufficient scientific evidence Antifungal treatment not in line with guidelines Detoxification therapy, e.g., with cholestyramine (CSM therapy) Dietary changes Homeopathic treatments Symbiosis controlTreatment methods without a medical or scientific basis Bioresonance therapy (Moratherapy) Autologous blood and urine treatment Holistic intestinal cleansing Salt therapy Clinical ecology procedures (e.g., provocation and neutralization test (PN test)) Table 13.Cochrane EBM Review by Sauni et al. (2011) [614] on the success of remediation measures after moisture or mold damage in relation to asthma and respiratory symptoms as well as the frequency of colds in adults and children. MeasureEffect on adultsEffect on childrenHome renovation (Evidence level: moderate)Wheezing (asthma): OR 0.64 (KI: 0.55 – 0.75) Rhinitis: OR 0.57 (CI: 0.55 – 0.66) Acute treatments (mean difference): MD –0.45 (KI: –0.76 – –0.14) Table 14.The authors’ declarations of conflicts of interest and their assessment are presented below: Consultant or expert activityCollaboration in a scientific advisory boardPaid lecturing or training activitiesPaid authors or co-author-shipResearch projects / conducting clinical studiesProprietary interests (patent, copyright, share ownership)Indirect interestsTopics of the guideline affected by COI; classification of the conflict of interest (IC) with regard to relevance, consequenceDr. med. Ute AurbachNoNoNoNoNoNoNoClassification: no IC Consequence: nonePriv.-Doz. Dr. med. Sven BeckerNoYesYesNoYesNoBoard member AeDAClassification: moderate IC; consequence: no voting authorization for allergological topicsProf. Dr. med. Romuald BellmannYesYesYesNoNoNoMandate holder ÖGMMClassification: moderate IC; consequence: no eligibility for antifungal therapyProf. Dr. med. Karl-Christian BergmannYesYesYesNoNoNoMandate holder DGPClassification: moderate IC; consequence: not eligible to vote on asthma-related issuesProf. Dr. med. Oliver A. CornelyYesYesYesNoNoNoNoClassification: moderate IC; consequence: no voting rights for mycosis-related topicsProf. Dr. med. Steffen EngelhartNoNoNoNoNoNoMandate holder GHUP and DGKH, Member of the Board GHUPClassification: no IC; Consequence: noneDr. rer. nat. Guido FischerNoNoNoNoNoNoNoClassification: no IC; Consequence: noneDr. rer. nat. Thomas GabrioNoNoNoNoNoNoNoClassification: no IC; Consequence: noneDr. med. Birger HeinzowNoNoNoNoNoNoNoClassification: no IC; Consequence: noneProf. Dr. med. Caroline E.W. HerrNoNoNoNoNoNoMandate holder and President of the GHUPClassification: no IC; Consequence: noneDr. rer. nat. Julia HurraßNoNoNoNoNoNoMandate holder and board member of the GHUPClassification: no IC; Consequence: noneDr. med. Marcus JoestNoNoYesNoNoNoNoClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. med. Christian KaragiannidisNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteProf. Dr. med. Ludger KlimekNoYesYesNoYesNoMandate holder AeDAClassification: moderate IC; consequence: no voting rights for immunotherapyDr. rer. nat. Martin KöberleNoNoYesNoNoNoMandate holder DDGClassification: low IC; consequence: no management function (coordination/AG management)Dr. rer. nat. Annette KolkNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteDr. med. Dipl.-Chem. Herbert LichtneckerNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteDr. med. Thomas Lob-CorziliusNoNoNoNoNoNoMandate holder GPAUClassification: no IC; Consequence: noneNorbert MülleneisenNoNoNoNoNoNoMandate holder DGPClassification: no IC; Consequence: noneProf. Dr. med. Dennis NowakNoNoYesNoNoNoDGAUM and DGP elected representativesClassification: low IC; consequence: no management function (coordination/AG management)Dr. med. Uta RabeNoNoYesNoNoNoMandate holder AeDAClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. rer. nat. Monika RaulfNoNoYesNoNoNoMandate holder DGAKI and DGAUMClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. med. Jörg SteinmannNoNoYesNoNoNoNoClassification: low IC; consequence: no management function (coordination/AG management)Prof. Dr. med. Jens-Oliver SteißNoNoYesNoNoNoMandate holder BAPPClassification: low IC; consequence: no management function (coordination/AG management)Dr. med. Jannik StemlerNoNoYesNoNoNoNoClassification: low IC; consequence: no management function (coordination/AG management)Dr. med. Ulli UmpfenbachNoNoNoNoNoNoBoard member BAPP, WAPPA, AGAS, FAAKClassification: no IC; Consequence: noneDr. rer. nat. Kerttu ValtanenNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedNot specifiedClassification: not possible; consequence: not entitled to voteDr. rer. nat. Sandra Walser-ReichenbachNoNoNoNoNoNoMandate holder GHUPClassification: no IC; Consequence: noneDr. rer. medic. Barbora WerchanNoNoNoNoNoNoNoClassification: no IC; Consequence: noneProf. Dr. med. Gerhard A. WiesmüllerNoNoNoNoNoNoMandate holder and Board member GHUPClassification: no IC; Consequence: noneProf. Dr. med. Birgit WillingerNoYesYesNoNoNoMandate holder DMykGClassification: low IC; consequence: no management function (coordination/AG management), (© Dustri-Verlag Dr. K. Feistle.)

Background: According to self-reported frequencies, every fifth or sixth dwelling in Germany is affected by dampness and/or mold. This carries a potential risk to health., Methods: This review is based on pertinent publications retrieved by a selective literature search and inquiry in the GENESIS database, on the AWMF guideline on the medical clinical diagnosis of indoor mold exposure, as updated in 2023, and on the relevant contents of other current guidelines. Based on this research, we present an algorithm for the evaluation of health problems that may be due to mold in indoor environments., Results: A rational diagnostic work-up begins with history-taking and physical examination, with attention to risk factors-above all, immune compromise and atopy. If there is evidence of atopy, targeted allergy diagnostics should be performed, consisting of a skin prick test and/or measurement of specific IgE antibodies, supplemented whenever indicated by provocative testing and cellular test systems. If the patient's immune response is compromised, the immediate cessation of mold exposure has absolute priority. Any suspected invasive fungal infection should be evaluated with radiological, microbiological, serological, and immunological testing. Indoor measurements of mold fungi, microbial volatile organic compounds (MVOC), and/or mycotoxins are generally not indicated as part of the medical evaluation; nor are blood or urine tests for particular mold components or metabolites., Conclusion: Mold in indoor environments should be dealt with by rapid exposure elimination for patients at risk, the rational diagnostic evaluation of any symptoms and signs of disease, and patient education about the possibilities and limitations of diagnostic testing and the generally limited utility of measurements in the affected interior spaces.

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.)

The European Confederation of Medical Mycology (ECMM), formed due to the surge in invasive fungal infections (IFI), initiated the Excellence Centers program in 2016 to guide stakeholders to leading medical mycology sites. This report focuses on the Cologne ECMM Excellence Center, recognized with Diamond status for active global involvement in 2017. The center offers free consultation via email and phone, responding within 24 h for life-threatening IFI, collecting data on origin, pathogens, infection details, and more. Over two years, 189 requests were received globally, predominantly from Germany (85%), mainly involving Aspergillus spp., Mucorales, and Candida spp. Fungal mixed infections occurred in 4% of cases. The center's service effectively addresses IFI challenges, advocating for a comprehensive study encompassing all ECMM Excellence Centers to enhance global mycological care. Proactive expansion of consultancy platforms is crucial, with future analyses needed to assess expert advice's impact on patient outcomes., (© 2024. The Author(s).)

Background: We assessed the laboratory diagnosis and treatment of invasive fungal disease (IFD) in Italy to detect limitations and potential for improvement., Methods: The survey was available online at www.clinicalsurveys.net/uc/IFI management capacity/, and collected variables such as (a) institution profile, (b) perceptions of IFD in the respective institution, (c) microscopy, (d) culture and fungal identification, (e) serology, (f) antigen detection, (g) molecular tests, (h) susceptibility testing and (i) therapeutic drug monitoring (TDM)., Results: The laboratory capacity study received responses from 49 Italian centres, with an equitable geographical distribution of locations. The majority of respondents (n = 36, 73%) assessed the occurrence of IFD as moderate-high, with Aspergillus spp. being the pathogen of highest concern, followed by Candida spp. and Mucorales. Although 46 (94%) of the institutions had access to microscopy, less than half of them performed direct microscopy on clinical specimens always when IFD was suspected. Cultures were available in all assessed laboratories, while molecular testing and serology were available in 41 (83%), each. Antigen detection tests and antifungal drugs were also generally accessible (> 90%) among the participating institutions. Nevertheless, access to TDM was limited (n = 31, 63%), with a significant association established between therapeutic drug monitoring availability and higher gross domestic product per capita., Conclusions: Apart from TDM, Italy is adequately prepared for the diagnosis and treatment of IFD, with no significant disparities depending on gross domestic product. Future efforts may need to focus on enhancing the availability and application of direct microscopic methods, as well as TDM, to promote optimal treatment and better patient outcomes., (© 2023. The Author(s).)

Background: Antifungal diagnostic capacity has been documented in various countries, there is a lack of comprehensive research on clinical mycology diagnostics and treatment in Hungary., Methods: We conducted an online survey encompassing questions that explored various aspects of the mycology diagnostic and antifungal therapy-related information. The survey aimed to gather details about institutional profiles, perceptions of invasive fungal infections (IFIs), and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring., Results: As of May 2023, a total of 17 institutions responded to the questionnaire. Seven participants categorized the institutional incidence of IFI as 'very low', four as 'low', and six as 'mild'. The majority of centers identified Candida spp. (94%) and Aspergillus spp. (82%) as the most prevalent fungal pathogens. Nearly half of the laboratories (47%) reported using matrix-assisted laser desorption/ionization-time of flight mass spectrometry for identification. All institutions had access to microscopy and culture-based diagnostic approaches. A significant number of centers had access to antigen detection (71%) and various molecular assays (59%). Regarding antifungal agents, all reporting sites used at least one triazole, with voriconazole (77%) being the most common mold-active azole. Furthermore, 71% of the centers applied at least one formulation of amphotericin B, and 65% to one echinocandin. However, only 18% of the centers used 5-flucytosine., Conclusion: Resource availability for diagnosing and treating IFI in Hungary varies across hospitals based on location. Surveys help identify gaps and limitations in this area. To address these challenges, interregional cooperation within Hungary could be a facilitating strategy., Competing Interests: RK has no conflict of interest. LM has received conference travel grants from MSD, Astellas, and Pfizer. JS has received research support from the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals Inc., outside the submitted work; has received speaker honoraria from Pfizer Inc., Gilead, and AbbVie, outside the submitted work; has been a consultant to Gilead, Produkt&Markt GmbH, Alvea Vax. and Micron Research, outside the submitted work; and has received travel grants by German Society for Infectious Diseases (DGI e.V.) and Meta-Alexander Foundation, 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 Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; 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, Shionogi; a patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7), outside of the submitted work. JSG reports speaker honoraria from Gilead and Pfizer, outside of the submitted work., (© The Author(s), 2023.)

Introduction: Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria., Methods: Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI&#95;management&#95;capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring., Results: Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites., Conclusion: Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)

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.)

SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73-86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67-89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77-94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies., (© 2023. The Author(s).)

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.)

The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as Aspergillus spp., Candida spp. and Pneumocystis jirovecii. In response to this, prophylactic and pre-emptive antifungal treatment strategies have been developed and implemented for high-risk patient populations. The benefit by risk reduction needs to be carefully weighed against potential harm caused by prolonged exposure against antifungal agents. This includes adverse effects and development of resistance as well as costs for the healthcare system. In this review, we summarise evidence and discuss advantages and downsides of antifungal prophylaxis and pre-emptive treatment in the setting of malignancies such as acute leukaemia, haematopoietic stem cell transplantation, CAR-T cell therapy, and solid organ transplant. We also address preventive strategies in patients after abdominal surgery and with viral pneumonia as well as individuals with inherited immunodeficiencies. Notable progress has been made in haematology research, where strong recommendations regarding antifungal prophylaxis and pre-emptive treatment are backed by data from randomized controlled trials, whereas other critical areas still lack high-quality evidence. In these areas, paucity of definitive data translates into centre-specific strategies that are based on interpretation of available data, local expertise, and epidemiology. The development of novel immunomodulating anticancer drugs, high-end intensive care treatment and the development of new antifungals with new modes of action, adverse effects and routes of administration will have implications on future prophylactic and pre-emptive approaches., Competing Interests: Declaration of competing interest RS has received speaker honoraria by Pfizer. DN has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. MO works as Scientific Support Representative for Taconic Biosciences GmbH. JP has received honoraria from Associates of Cape Cod, Gilead Sciences, Swedish Orphan Biovitrum, and Pfizer, research funding from Merck & Co., and Pfizer and is a stakeholder of AbbVie Inc., and Novo Nordisk. 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, Pardes, 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, and EasyRadiology. JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals Inc.; has received speaker honoraria by Pfizer Inc., Gilead and AbbVie; 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 e.V.) and Meta-Alexander Foundation. JAN and IR have nothing to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With increasing frequency, clinical and laboratory-based mycologists are consulted on invasive fungal diseases caused by rare fungal species. This review aims to give an overview of the management of invasive aspergillosis (IA) caused by non- fumigatus Aspergillus spp.-namely A. flavus , A. terreus , A. niger and A. nidulans -including diagnostic and therapeutic differences and similarities to A. fumigatus . A. flavus is the second most common Aspergillus spp. isolated in patients with IA and the predominant species in subtropical regions. Treatment is complicated by its intrinsic resistance against amphotericin B (AmB) and high minimum inhibitory concentrations (MIC) for voriconazole. A. nidulans has been frequently isolated in patients with long-term immunosuppression, mostly in patients with primary immunodeficiencies such as chronic granulomatous disease. It has been reported to disseminate more often than other Aspergillus spp. Innate resistance against AmB has been suggested but not yet proven, while MICs seem to be elevated. A. niger is more frequently reported in less severe infections such as otomycosis. Triazoles exhibit varying MICs and are therefore not strictly recommended as first-line treatment for IA caused by A. niger , while patient outcome seems to be more favorable when compared to IA due to other Aspergillus species. A. terreus -related infections have been reported increasingly as the cause of acute and chronic aspergillosis. A recent prospective international multicenter surveillance study showed Spain, Austria, and Israel to be the countries with the highest density of A. terreus species complex isolates collected. This species complex seems to cause dissemination more often and is intrinsically resistant to AmB. Non- fumigatus aspergillosis is difficult to manage due to complex patient histories, varying infection sites and potential intrinsic resistances to antifungals. Future investigational efforts should aim at amplifying the knowledge on specific diagnostic measures and their on-site availability, as well as defining optimal treatment strategies and outcomes of non- fumigatus aspergillosis.

Infections represent one of the most frequent complications during therapy of acute myeloid leukemia (AML). In addition to associated prolonged phases of neutropenia, damage to the mucosal barrier by cytotoxic agents favors infections caused by endogenous pathogens. The source often remains unknown with bacteremia being the most common evidence of infection. Infections with gram-positive bacteria predominate, however, infections with gram-negative bacteria more often lead to sepsis and death. Due to prolonged neutropenia, patients with AML are furthermore at risk for invasive fungal infections. Viruses, on the other hand, are rarely the cause of neutropenic fever. Because of the limited inflammatory response in neutropenic patients, fever is often the only sign of infection and therefore always represents a hematologic emergency. Prompt diagnosis and initiation of an adequate anti-infective therapy are critical to avoid progression to sepsis and possibly death., Competing Interests: JS hat Vortragshonorare von Gilead, Pfizer und AbbVie erhalten., (Thieme. All rights reserved.)

Purpose: We hypothesized that SARS-CoV-2 infection numbers reported by governmental institutions are underestimated due to high dark figures as only results from polymerase chain reaction (PCR) tests are incorporated in governmental statistics and testing capacities were further restricted as of July, 2022., Methods: A point prevalence investigation was piloted by rapid antigen testing (RAT) among participants of the VACCELERATE volunteer registry. 2400 volunteers were contacted, of which 500 received a RAT including instructions for self-testing in the first week of July, 2022. Results were self-reported via e-mail., Results: 419 valid RAT results were collected until July 7th, 2022. Between July-1 and July-7, 2022, 7/419 (1.67%) tests were positive. Compared to reports of the German Federal Government, our results suggest a more than twofold higher prevalence. Three out of seven positive individuals did not have a PCR test and are therefore likely not to be displayed in governmental statistics., Conclusion: Our findings imply that the actual prevalence of SARS-CoV-2 may be higher than detected by current surveillance systems, so that current pandemic surveillance and testing strategies may be adapted., (© 2022. The Author(s).)

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual's medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year., Methods/design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed., Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population., Trial Registration: ClinicalTrials.gov NCT05160766 . Registered on 16 December 2021., Protocol Version: V06&#95;0: 27 July 2022., (© 2022. The Author(s).)

Background: Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients., Objectives: To analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections., Methods: A systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies' references. Cases from the FungiScope® registry were added to a combined analysis., Results: We identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived., Conclusions: Despite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: The use of routine data will be essential in future healthcare research. Therefore, harmonizing procedure codes is a first step to facilitate this approach as international research endeavour. An example for the use of routine data on a large scope is the investigation of surgical site infections (SSI). Ongoing surveillance programs evaluate the incidence of SSI on a national or regional basis in a limited number of procedures. For example, analyses by the European Centre for Disease Prevention (ECDC) nine procedures and provides a mapping table for two coding systems (ICD9, National Healthcare Safety Network [NHSN]). However, indicator procedures do not reliably depict overall SSI epidemiology. Thus, a broader analysis of all surgical procedures is desirable. The need for manual translation of country specific procedures codes, however, impedes the use of routine data for such an analysis on an international level. This project aimed to create an international surgical procedure coding systems allowing for automatic translation and categorization of procedures documented in country-specific codes., Methods: We included the existing surgical procedure coding systems of five European countries (France, Germany, Italy, Spain, and the United Kingdom [UK]). In an iterative process, country specific codes were grouped in ever more categories until each group represented a coherent unit based on method of surgery, interventions performed, extent and site of the surgical procedure. Next two ID specialist (arbitrated by a third in case of disagreement) independently assigned country-specific codes to the resulting categories. Finally, specialist from each surgical discipline reviewed these assignments for their respective field., Results: A total number of 153 SALT (Staphylococcus aureus Surgical Site Infection Multinational Epidemiology in Europe) codes from 10 specialties were assigned to 15,432 surgical procedures. Almost 4000 (26%) procedure codes from the SALT coding system were classified as orthopaedic and trauma surgeries, thus this medical field represents the most diverse group within the SALT coding system, followed by abdominal surgical procedures with 2390 (15%) procedure codes., Conclusion: Mapping country-specific codes procedure codes onto to a limited number of coherent, internally and externally validated codes proofed feasible. The resultant SALT procedure code gives the opportunity to harmonize big data sets containing surgical procedures from international centres, and may simplify comparability of future international trial findings., Trial Registration: The study was registered at clinicaltrials.gov under NCT03353532 on November 27 th , 2017., (© 2022. The Author(s).)

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.)