Zusammenfassung Mehrere Spezies wurden neu klassifiziert, darunter klinisch relevante Spezies wie C. glabrata (Nakaseomyces glabratus), C. krusei (Pichia kudriavzevii) und C. auris (Candidozyma auris). Die neue Leitlinie empfiehlt, für die nächsten Jahre in Befunden beide Bezeichnungen zu nennen. C. auris zeigt eine hohe Umweltstabilität, ist häufig multiresistent gegenüber Antimykotika und ist weltweit Auslöser zahlreicher Ausbrüche. Der Nachweis aus sterilen Materialien ist in Deutschland seit 2023 meldepflichtig. Ein Zuwachs an resistenten C.-auris-Isolaten ist in Deutschland zu erwarten. In Berlin wurde zwischen 2018 und 2022 ein Ausbruch mit einem Fluconazol-resistenten C.-parapsilosis-Stamm nachgewiesen. Eine Verwandtschaft der Isolate wurde molekulargenetisch nachgewiesen. Bei C. tropicalis und C. glabrata nehmen Resistenzen gegen die häufig eingesetzten Azol-Antimykotika weltweit zu. Bei C. glabrata werden darüber hinaus zunehmende Resistenzen gegen die Erstlinientherapie mit Echinocandinen beobachtet, wodurch die Therapiemöglichkeiten erheblich beeinträchtigt werden. Für C. auris hat EUCAST erstmals Breakpoints für die Echinocandine Anidulafungin und Micafungin sowie für Amphotericin B eingeführt. Für Amphotericin B wurde die gesamte Wildtyp-Population als „empfänglich bei erhöhter Exposition“ (Susceptible, increased Exposure, I) eingestuft. Eine antimykotische Prophylaxe mittels Azol-Antimykotika wird bei Hochrisikopatienten oder bei Neutropenie empfohlen. Bei Vorliegen einer Azol-Resistenz kommen Echinocandine zum Einsatz. Für die Erstlinientherapie der Candidämie wird der Einsatz von Echinocandinen empfohlen. In der Klasse der Echinocandine wurde 2024 das neue Echinocandin Rezafungin zugelassen, welches nur einmal wöchentlich infundiert werden muss. Neue Substanzen wie Fosmanogepix und Ibrexafungerp bieten vielversprechende, neue Therapieoptionen zur Therapie von Candida-Infektionen und werden das Antimykotika-Portfolio zukünftig erweitern.

Background: The therapeutic landscape of hematological malignancies has expanded rapidly, increasing survival but also exposing patients to pharmacokinetic variability and clinically relevant drug-drug interactions. Therapeutic drug monitoring (TDM) offers a pharmacokinetics-informed strategy to individualize dosing, yet its real-world implementation across drug classes and healthcare settings remains insufficiently characterized. Methods: We conducted an international, cross-sectional online survey (December 2023-February 2024) assessing availability, utilization, and clinical impact of TDM in patients with hematological malignancies. Physicians from multiple specialties reported institutional practices, turnaround times, drug-specific monitoring strategies, and treatment modifications based on TDM results. Results: A total of 209 physicians from 32 countries participated, predominantly from Europe (92%). TDM was widely accessible (97%), mainly performed onsite (79%), and perceived as beneficial by nearly all respondents (99%). Routine TDM was most frequently used for classical agents (methotrexate, cyclosporin A), antifungals, and antibiotics, but substantial interest was reported for targeted therapies, including BCL-2 inhibitors, BCR-ABL tyrosine kinase inhibitors, FLT3 inhibitors, and Bruton tyrosine kinase inhibitors. Treatment was modified based on TDM results by 71% of respondents, with faster turnaround times strongly associated with clinical action. Limited assay availability, delayed reporting, and insufficient clinical evidence were identified as key barriers to broader implementation. Conclusions: TDM is widely available and perceived as clinically useful in the management of hematological malignancies, frequently informing treatment decisions. While firmly established for classical agents and anti-infectives, clinicians express growing interest in extending TDM to targeted therapies. Optimizing turnaround times, expanding assay availability, and integrating pharmacokinetics-informed dosing into clinical trials may further clarify the role of TDM within precision medicine approaches in hematology.

BACKGROUND:Lipoedema is a painful, chronic disease of the subcutaneous adipose tissue, predominantly affecting women. Conservative complex decongestive therapy is the standard of care but offers limited symptom relief. Liposuction appears to be a promising approach but lacks evidence of effectiveness and safety. The aim of this trial was to show superiority of liposuction compared with conservative therapy regarding relevant pain reduction with reasonable safety. METHODS:In this multicentre, randomised controlled trial at 11 German centres, eligible women with stage I, II, or III lipoedema and leg pain of at least 4 points on a 0-10 numeric rating scale received conservative therapy for up to 7 months and then were randomly assigned to liposuction or conservative therapy (2:1) stratified by lipoedema stage and study site. For all visits involving an assessment, patches were applied to the legs of all patients, and patients were instructed not to reveal the treatment they had received, in order to mask the assessor. The primary endpoint was reduction of patient-reported leg pain by at least 2 points after 12 months, and missing assessment was considered non-successful.The primary outcome was analysed in the intention-to-treat population which included all randomly assigned patients, and safety analysis included all enrolled patients. A long-term follow-up of 36 months is ongoing. This study is registered at ClinicalTrials.gov, NCT04272827. FINDINGS:Of 1973 patients screened between Jan 19, 2021, and June 7, 2022, 453 were enrolled, and 410 were randomly assigned to the liposuction group (n=278) or to the conservative therapy group (n=132). All 410 patients were included in the intention-to-treat analysis (mean age 42·9 [ SD 10·6]; ethnicity data were not collected). After 12 months, 190 (68%) of 278 randomisly assigned patients undergoing liposuction achieved the primary endpoint of pain reduction versus ten (8%) of 132 randomly assigned to conservative therapy (odds ratio 26·2 [95% CI 13·1-52·5]; p<0·0001). Adverse events occurred in 124 (47%) of 265 patients undergoing liposuction, and 20 (8%) of 265 were rated as serious. In the conservative therapy group, 30 (21%) of 145 patients reported adverse events, and five (3%) 145 were rated as serious. Secondary endpoints regarding quality of life showed greater improvement in the liposuction group. INTERPRETATION:Liposuction was superior to conservative therapy in reducing leg pain and improving quality of life in patients with lipoedema, but was associated with a higher rate of serious adverse events. Liposuction has the potential to be a promising treatment option for patients with lipoedema. FUNDING:The Federal Joint Committee, Germany.

Background/Objectives: Primary amoebic meningoencephalitis (PAM) is a rare, fulminant, and often fatal central nervous system infection caused by the opportunistic free-living amoeba Naegleria fowleri. Although Naegleria species are widely present in freshwater and soil worldwide, human disease is associated specifically with pathogenic N. fowleri rather than the many nonpathogenic environmental species, and virulence may vary across N. fowleri isolates. This systematic review aimed to synthesize contemporary global data from 2000 to 2024 to identify recent trends in epidemiology, clinical presentation, diagnosis, treatment, and outcomes. Methods: A systematic literature search was conducted across PubMed, Scopus, and the Cochrane Library, identifying 58 eligible publications encompassing 66 individual cases. Results: Most reports originated from the United States, India, and China. The median patient age was 14 years, with 78% of cases occurring in males. Annual case reports increased from one per year (2000–2005) to over four per year (2020–2024), reflecting either a true rise in incidence or improved detection. Common presenting symptoms included fever, headache, and altered mental status. Diagnosis was confirmed via polymerase chain reaction (PCR) testing or post-mortem biopsy in nearly one-third of cases. Treatment regimens varied, with amphotericin B and miltefosine being the most frequently used agents. Overall mortality was 83%, with survival strongly associated with early initiation of combination therapy. Pediatric patients had a higher survival rate (22%) compared to adults (7.1%). Conclusions: The findings highlight the need for heightened clinical awareness, especially in the context of climate-driven ecological changes that may expand N. fowleri’s geographic range. This review underscores critical gaps in surveillance and diagnostics and emphasizes the importance of a One Health approach to addressing emerging threats like PAM. Further research into novel therapeutics, rapid diagnostics, and global case reporting systems is urgently needed.

Candida species cause life-threatening bloodstream infections, particularly in critically ill and immunocompromised patients. Although guideline adherence has been shown to improve outcomes, real-world implementation is often constrained. This cross-sectional, web-based survey evaluated current clinical practices and barriers in candidemia management across German healthcare institutions. A structured questionnaire based on the EQUAL Candida score was disseminated online from 10/2023 to 07/2025. Physicians involved in candidemia management reported institutional characteristics, diagnostic practices, antifungal treatment strategies, central line management, and follow-up practices. Data were analyzed using descriptive statistics and chi-square testing. A total of 217 physicians from 147 institutions participated, with 74.5% of participants affiliated with large care facilities. Caspofungin was the predominant first-line therapy (81.4%), whereas fluconazole was used by 5.3% of participants. First-line choice did not differ by years of clinical experience (P = 0.194). Echocardiography was routinely performed by 57% of participants; selective use showed no association with years of clinical experience (P = 0.845) or annual number of candidemia cases (P = 0.089). Ophthalmoscopy was performed routinely by 37% of participants and showed no association with experience (P = 0.907), but was significantly associated with lower annual caseload (P = 0.02) and infectious disease speciality (P = 0.003). Central line removal or replacement within 24 h was reported by 82.5%. Follow-up blood cultures were obtained daily by 31.4%, while 54.8% repeated cultures every 48 h. While core candidemia management practices are generally well implemented in German healthcare institutions, certain recommended diagnostic steps remain underutilized. Targeted educational and structural interventions are needed to strengthen guideline adherence and optimize patient outcomes across diverse settings.

The fungus Aspergillus fumigatus has evolved as an important cause of opportunistic fungal diseases in humans worldwide. It is the most frequent filamentous fungus colonizing the airways of patients with cystic fibrosis and can affect immunocompetent as well as immunocompromised individuals. Aspergillus disease is commonly treated with azoles, which inhibit lanosterol 14α-demethylase, a key component of the ergosterol biosynthesis pathway, essential for membrane integrity and fluidity. Lanosterol 14α-demethylase is encoded by the CYP51A gene. Azole-resistant A. fumigatus isolates often show amino acid substitutions in Cyp51A. Most prevalent mutations have a tandem repeat (TR) in the promoter and point mutations in the gene (e.g. TR34/L98H and TR46/Y121F/T289A). In addition to TRs, isolates with single point mutations developed and are widespread around the world (e.g. M220I, G54R). To date, azole-resistant isolates have been found on every continent except Antarctica. This review will summarize the epidemiology and prevalence of Azole-resistant A. fumigatus worldwide including the history of different mutations found and highlights important gaps as data are missing in several parts of the world.

ABSTRACT Accurate interpretation of antifungal minimum inhibitory concentrations (MICs) requires distinguishing species-level intrinsic phenotypes from isolate-level acquired resistance. Many fungi exhibit intrinsic reduced susceptibility (IRS) reflected by wild-type (WT) MIC distributions that are shifted toward higher values (uniformly or with a high-MIC tail). This may lead to the misclassification of high-end WT isolates as resistant and compromise surveillance and cross-center comparability, particularly for rare fungi lacking established breakpoints. In this review, we propose a pragmatic and standardized framework to distinguish intrinsic phenotypes (normal susceptibility, IRS, intrinsic resistance) from acquired resistance based on species-specific WT MIC distributions and standardized WT/non-wild-type (NWT) reporting. This framework is specifically intended to guide interpretation in data-limited settings where WT distributions and epidemiological cut-off values (ECOFFs) are not yet established. MICs within the unimodal species-specific WT range, even if high, should be interpreted as potentially reflecting IRS and not as acquired resistance. Only MICs clearly right-shifted beyond the WT range should be classified as NWT by epidemiological cut-off values or, if unavailable, as putative NWT, and considered candidates for acquired resistance. When breakpoints are lacking, WT versus NWT reporting with explicit comments on IRS/intrinsic resistance is preferable to forced susceptible/resistant (S/R) categorization. In the absence of established WT distributions or ECOFFs, such classification remains provisional and should rely on descriptive MIC patterns, available data sets, and clinical context. Integrating these biological interpretations with pharmacokinetics/pharmacodynamics and clinical context supports optimized dosing, avoids inappropriate drug exclusion, and enables consistent surveillance and multicenter comparisons.

BACKGROUND:Infections with respiratory viruses such as SARS-CoV-2 and influenza are significant international public health concerns. While patients with cancer remain the most vulnerable group, they show poor vaccine response in general. Immunological data in this population are limited and mainly focus on serological parameters. However, in these patients, cellular, and especially T-cell, responses often seem to be induced more reliably than humoral responses. OBJECTIVE:To gain further insights into vaccine-induced immunity, the RESPONSE study will analyze the effect of early and late booster vaccination on humoral and cellular responses, with special focus on T cell-induced immune responses. In addition, we aim to investigate factors influencing humoral and cellular vaccine-induced immunity in patients with hematological and oncological malignancies, including state of disease, treatment, and demographic factors. METHODS:Humoral immune responses will be assessed by measuring binding and neutralizing antibodies using standardized assays. Cellular immunity will be evaluated using functional assays such as flow cytometry and FluoroSpot, as well as in-depth analyses using additional exploratory assays as appropriate. Immune responses will be correlated with clinical parameters, including disease status, treatment, and demographic factors. RESULTS:This study was initiated following ethics approval and is currently recruiting participants. Enrollment commenced on March 25, 2025, and is ongoing, whereas biosample collection and follow-up visits are nearing completion for most participants. Final data cleaning, dataset integration, and statistical analyses of adaptive immune responses are planned from the third quarter of 2026 onward. CONCLUSIONS:This study intends to lay a foundation for a structured translational research platform on vaccination to aim for best protection from infection by different respiratory pathogens. Long-term objectives are reaching best possible protection from vaccine-preventable disease with a first focus on influenza infection. In addition, we plan to investigate vaccine-induced immune responses to the recently approved respiratory syncytial virus vaccine using this platform and possibly extend this to further vaccines in the future. Urgent questions, such as the influence of different targeted therapies on vaccine immune response, will be part of these projects. TRIAL REGISTRATION:ClinicalTrials.gov NCT06612515; https://clinicaltrials.gov/study/NCT06612515. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/88520.

Acute respiratory infections (ARI) impose a significant burden on healthcare systems and society. This study aimed to investigate the circulation of respiratory viruses in community-dwelling older adults in Germany. Participants aged ≥ 50 years in Germany performed multi-pathogen rapid antigen self-tests (MAK5) detecting adenovirus (AdV), severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), influenza A and B, and respiratory syncytial virus (RSV) on June 1 and December 15, 2024. Participants reported test results, ARI symptoms and duration, medical consultations, work absenteeism, comorbidities, vaccination history, and prior infections. 2,654 participants enrolled in the point prevalence assessment on June 1, 2024 and 2,385 on December 15, 2024. Most tests were negative (n = 4,807; 93.9

Background Human metapneumovirus (hMPV) is an increasingly recognized respiratory pathogen in immunocompromised patients, but its impact in haematological malignancies is poorly defined. Unlike influenza or SARS-CoV-2, hMPV has no specific treatment or vaccine, contributing to underdiagnosis and underestimation of its clinical relevance.Method We performed a multicentre retrospective cohort study within the Epidemiology of COVID-19 in patients with hematological malignancies: A European Haematology Association Survey/ Epidemiology of respiratory viral infections in patients with hematological malignancies: A European Haematology Association Survey registry of haematological patients with hMPV (January 2023-December 2024), comparing clinical features and outcomes with matched influenza and SARS-CoV-2 cohorts.Results The study included 130 patients with hMPV. Median age was 58.5 years; 57% were male. Plasma cell neoplasms (25%), lymphoma (23%), and acute myeloid leukemia (20%) were the most common hematological malignancies. Hospitalization occurred in 64%, intensive care unit (ICU) admission in 19%, and 30-day mortality was 8%. Most cases (73%) received supportive care only. Secondary infections were common (24%). Chronic renal disease significantly increased mortality risk (hazard ratio 20.9 11.05, P = .014). Compared with influenza and SARS-CoV-2, hMPV patients had comparable severity and outcomes, with 18.5% ICU admission rates versus 25.9% for influenza (P = .316) and 20.9% versus 4.7% for SARS-CoV-2 (P = .006), and 30-day mortality of 5.6% versus 11.1% for influenza (P = .489) and 7.0% versus 2.3% for SARS-CoV-2 (P = .277), yet received fewer targeted interventions.Conclusions hMPV causes clinically significant disease in patients with hematological malignancy, often necessitating hospital and ICU care, and leading to mortality. In the absence of specific treatments or vaccines, this virus remains an underrecognized pathogen in patients with hematological malignancy. Enhanced clinical awareness and investment in diagnostics, prevention, and therapeutics are needed.

Drug-resistant fungal disease must be addressed in the 2026 update to the Global Action Plan on Antimicrobial Resistance

BACKGROUND:One of the most neglected, yet rapidly developing, areas of concern in global health is the changing epidemiology of fungal infections. OBJECTIVES:The purpose of this narrative review was to draw attention to the pressing need for both a better understanding of the ecological, environmental, and host-related mechanisms underlying these emerging phenomena as well as a greater awareness of the growing clinical and public health significance of fungal diseases. It also highlights the significance of equitable access to fungal diagnostics and antifungal treatments, as well as coordinated surveillance across the One Health framework's environmental, animal, and human interfaces. SOURCES:This review is based on a narrative synthesis of recent literature on emerging mycoses, including epidemiological studies, clinical reports, and global health analyses addressing environmental drivers, pathogen evolution, and health system preparedness. CONTENT:Although many of the causative agents are well-known environmental pathogens, climate change, deforestation, increased human mobility, growing immunosuppressed populations, and ill-equipped healthcare infrastructures are all contributing to fungi emerging as serious public health risks. Blastomyces helicus (formerly B. dermatitidis), Candidozyma auris (formerly Candida auris), Emergomyces spp., and Sporothrix brasiliensis are a few examples of mycoses with changing epidemiological patterns. IMPLICATIONS:Fungal diseases continue to be neglected in international health policies and inadequately incorporated into frameworks for pandemic preparedness, despite their increasing clinical and ecological significance. The world community runs the risk of entering the next era of infectious threats unprepared for the expanding fungal frontier if concurrent investments are not made in clinical training, infection prevention and control, and health system readiness.

OBJECTIVES:We aimed to systematically assess acute respiratory infection (ARI) episodes outside medical settings in older adults in Germany to capture real-time, community-based data on incidences, symptoms, healthcare use, and work absenteeism. METHODS:German adults aged ≥50 years enrolled in the VACCELERATE Volunteer Registry received multipathogen antigen test kits (MAK5) for self-testing, detecting SARS-CoV-2, influenza A and B viruses, respiratory syncytial virus (RSV), and adenovirus (AdV). From May 2024 to May 2025, participants self-tested upon ARI symptoms and reported test results, symptoms, episode duration, medical consultations, illness-related work absenteeism, pre-existing conditions, vaccination history, and previous infections. RESULTS:Of 3162 individuals enrolled, 2890 (91.4%) actively participated. Overall, 45.5% (1314 of 2890) reported no ARI, 31.4% (908 of 2890) 1, and 22.8% (658 of 2890) ≥2 episodes (median: 2; interquartile range [IQR]: 1-3; range: 0-6). Among 2569 tests, 752 (29.3%) were positive, including 53 (7.0%) codetections, yielding 833 pathogen detections. Cumulative incidence was 18.5% (524 of 2890) for SARS-CoV-2, 4.0% (114 of 2890) for AdV, 3.8% (110 of 2890) for influenza A virus, 1.8% (52 of 2890) for RSV, and 1.1% (33 of 2890) for influenza B virus. Median ARI duration ranged from 6 days (IQR: 5-8 days, range: 1-20 days) for SARS-CoV-2 to 9 days (IQR: 5-15 days, range: 1-26 days) for RSV. Median age ranged from 56 years (IQR: 54 -61 years; range: 50-80 years) for AdV to 61 years (IQR: 56-67 years; range: 51-81 years) for RSV. Medical consultation occurred in 28.8% (15 of 52) RSV, and 15.3% (80 of 524) SARS-CoV-2 cases. SARS-CoV-2 detections accounted for 31.1% (222 of 713) of illness-related work absences and 2 of 9 (22.2%) hospitalizations. CONCLUSIONS:This study enabled real-time, community-based monitoring of five endemic pathogens. Although SARS-CoV-2 accounted for highest cumulative incidence and overall disease burden, RSV detections, though less frequent, were predominantly observed in older adults and were associated with greater per-case burden, reflected in longer illness duration and increased healthcare utilization.

BackgroundDespite the vast growth of vaccine studies during the SARS-CoV-2 pandemic, clinical trials failed to adequately represent diverse societal groups, resulting in the underrepresentation of specific populations. Understanding the factors hampering participation in vaccine clinical trials is essential to better identify structural, ethical, and communication barriers and to improve inclusive strategies for broader and more equitable participation in future vaccine research. ObjectiveThis study aimed to identify the perceived barriers to participation in vaccine trials among pregnant and lactating women, children aged younger than 18 years, and adults aged older than 65 years, as reported by professionals with expertise in vaccines or vaccine trials. MethodsAn online questionnaire was developed to gather personal information, group-specific barriers to vaccine trial participation, and suggestions to overcome these barriers. Data are presented as absolute (n/N) and relative frequencies (%). ResultsA total of 115 respondents, the majority (n=73, 63.5%) of whom were working in the scientific community, completed the online survey. Challenges in recruiting children were identified due to “safety or efficacy concerns,” “difficulties about ethics and regulatory issues,” and “lack of targeted information and communication.” Challenges in recruiting pregnant and lactating women were primarily “ethics and regulatory requirements,” “safety issues,” and “lack of prioritization or interest.” “Lack of information and communication channels adapted to the specific target group,” along with “lack of prioritization,” were the main challenges in recruiting older participants. Provision of health-related incentives, including but not limited to access to new treatments and receiving expert medical care, seems to be the top-rated motivation to participate in vaccine clinical trials. ConclusionsThe main challenges in recruiting pregnant and lactating women and children in vaccine trials involve safety and efficacy concerns, as well as lengthy ethical and regulatory processes. For older adults, key issues include poor communication channels tailored to their needs, limited information, lack of prioritization, funding, infrastructure, and industry interest. Across all underrepresented groups, low awareness of and poor communication about research opportunities were major barriers. Additionally, mobility issues affected older adults, while lack of motivation and incentives affected children, and low health literacy and provider uncertainty impacted pregnant and lactating women. Improving communication infrastructure and enhancing communication strategies with clear, tailored messages to build trust and motivate participation are essential to improve inclusion in vaccine research.

Patienten mit hämatologischen und onkologischen Erkrankungen haben ein erhöhtes Risiko für schwere Verläufe und eine erhöhte Mortalität impfpräventabler Infektionen. Gleichzeitig weisen die Betroffenen eine gestörte Immunität auf. Art und Grad der Immundefizienz werden neben der Grunderkrankung und ihrer Therapie von Komorbiditäten bestimmt. Obwohl diese Patientengruppe regelhaft aus Zulassungsstudien neuer Vakzine ausgeschlossen wird, konnte in den vergangenen Jahren – insbesondere durch die COVID-19-Pandemie angeregt – eine robuste Datenbasis für Impfempfehlungen entwickelt werden. Wir hoffen, durch Fokussierung auf die wichtigsten Impfungen und pragmatische Empfehlungen die Umsetzung für klinisch Tätige zu erleichtern.

ABSTRACT To determine midostaurin and posaconazole plasma concentrations and investigate adverse events (AEs) resembling drug-drug interactions (DDI) when both drugs were administered concomitantly during induction chemotherapy for acute myeloid leukemia (AML). Patients with FLT3-mutated AML who received midostaurin and posaconazole concomitantly between May 2019 and December 2022 were included and followed up to March 2023. Twice-weekly trough levels for midostaurin and posaconazole were measured with validated liquid chromatography–tandem mass spectrometry methods. Potential DDIs were independently reviewed by two physicians and attributed using the Drug Interaction Probability Scale (DIPS). Population pharmacokinetics analysis was done via nonlinear mixed-effect modeling. In 29 patients, concentrations ranged from 0.6 to 24.5 mg/L for midostaurin and from <30 to 2,572 µg/L for posaconazole. A total of 375 AEs in 66 midostaurin cycles, with 280 AEs classified as grade ≥3, were recorded. Probable DDI with a DIPS score of ≥5 was attributed in 14/375 AEs; no highly probable AEs were registered. Eight AEs led to dose modification or discontinuation of midostaurin in seven patients. Clearance for midostaurin during co-administration with posaconazole was 0.52 L/h (95% CI, 0.42–0.62 L/h). A breakthrough fungal infection was recorded in eight patients (27.5%). DDI of midostaurin and posaconazole is clinically meaningful but infrequent. High inter- and intra-individual variabilities of midostaurin and posaconazole plasma exposure were observed. Midostaurin clearance was delayed during co-administration. Midostaurin therapeutic drug monitoring may serve for decision-making when DDI with CYP3A4 inhibitors is suspected.

BACKGROUND:Candida infections are a leading cause of invasive fungal disease (IFD), especially among critically ill and immunocompromised patients. Despite available pathogen-directed antifungal therapies, outcomes remain unsatisfactory with high associated morbidity and mortality rates. Increasing recognition of immune dysregulation of the host, including immunoparalysis and impaired antifungal effector responses, has driven interest in immunotherapeutic strategies as adjuncts to conventional treatment. OBJECTIVES:To provide a comprehensive overview of emerging immunotherapeutic approaches for invasive Candida infections and evaluate their mechanistic rationale, current evidence, and potential for clinical translation. SOURCES:Relevant literature was identified through a focused search of PubMed/MEDLINE, Embase, and ClinicalTrials.gov, supplemented by the authors' personal collection of key studies and reference screening. CONTENT:Immunotherapeutic strategies targeting invasive Candida infections encompass both non-cellular and cellular approaches. Cytokine-based therapies, including interferon-gamma and granulocyte/macrophage colony-stimulating factors, aim to restore impaired innate immunity and have demonstrated preliminary clinical benefits in selected populations. Immune checkpoint inhibitors represent a novel strategy to reverse T-cell exhaustion, supported by preclinical data but with limited clinical evidence to date in IFD. Cellular therapies, such as granulocyte transfusions, adoptive T-cell transfer, and engineered CAR T and CAR NK cells, offer innovative means to augment antifungal immunity, though their use remains largely preclinical. Preventive and therapeutic strategies involving vaccines and monoclonal antibodies are advancing, with several candidates showing promising immunogenicity and antifungal activity in preclinical and early clinical studies. IMPLICATIONS:Immunotherapy has the potential to transform the management of invasive candidiasis by complementing antifungal therapy with host-directed interventions. Successful clinical translation will require real-time biomarker-driven patient stratification and rigorous safety evaluations to account for the heterogeneity of patients according to their immune status. Future research should prioritize adaptive, mechanism-based trial designs to enable precision immunotherapy and improve outcomes in high-risk populations.

Abstract Invasive fungal diseases (IFD) pose a major health challenge in Latin America and the Caribbean (LAC), particularly in vulnerable populations. A cross-sectional, survey is distributed between April 2023 and May 2025 to institutions involved in IFD diagnosis or care across LAC. The questionnaire evaluates diagnostic tools, antifungal availability, and therapeutic drug monitoring (TDM). A total of 619 institutions from 23 countries across LAC participate. Candida spp. (92%) and Aspergillus spp. (54%) are most frequently reported as major fungal threats. Culture (90%) is widely available, whereas access to galactomannan (41%), β-D-glucan (29%), and molecular testing (23%) is considerably lower. Availability of antifungals, including liposomal amphotericin B (38%), echinocandins (51%), voriconazole (57%) or posaconazole (33%) is significantly higher in countries with GDP per capita >US$ 10,000, in transplant centres, and in institutions managing people living with HIV. Therapeutic drug monitoring is available in only 36% of centres. Major diagnostic and treatment gaps persist in low-income countries, particularly in access to tools for identifying endemic mycoses. Substantial disparities exist in IFD diagnostic and treatment capacity across LAC, primarily driven by national income and institutional complexity. Strengthening laboratory infrastructure, antifungal access, and integration of fungal disease management into public health systems is urgently needed.

The Infectious Diseases Working Party (AGIHO) was established in 1996 as one of the subgroups of the German Society of Hematology and Medical Oncology (DGHO). Marking its 30th anniversary this year, the AGIHO reflects on a period of significant achievement and growth. Beyond its core mission of developing evidence-based clinical practice guidelines for the prevention, diagnosis, and management of infections in patients with cancer, the AGIHO has evolved into a vital platform for clinical trials, collaborative research, and postgraduate medical education. To ensure long-term sustainability and foster emerging talent, “Young AGIHO” was launched in 2023. This initiative aims to strengthen networking among early career physicians specializing in hematology and oncology with a strong focus on infectious diseases. The working party has also expanded its geographical footprint by integrating colleagues from Austria and Switzerland, thereby enhancing its international presence. Through the publication of guidelines in high-ranking international journals, AGIHO visibility has increased significantly. Representatives of the working party now serve as experts for scientific and health policy committees both nationally and internationally. As one of the DGHO's largest and most active subgroups, the AGIHO is ideally positioned to address future challenges in the field.