Despite an unremarkable clinical presentation an invasive bacterial infection (IBI; bloodstream infection or bacterial meningitis) is present in 1-4% of cases of fever without a source in neonates and young infants. Following the publication of the first international guidelines based on large registry studies (USA, Spain, UK), the 8th edition of the German Society for Pediatric Infectious Diseases (DGPI) Handbook proposes a standardized approach to risk stratification for this vulnerable patient group. The goal is the safe reduction of unnecessary diagnostics, antibiotic treatment and hospitalization. Specific decision algorithms based on clinical symptoms, age, urinalysis, viral testing and the biomarkers C-reactive protein (CRP), procalcitonin (PCT) and the number of neutrophils (ANC) enable under defined conditions a stepwise management strategy for well-appearing infants > 28 days old without lumbar puncture and antibiotic treatment and if necessary outpatient follow-up.

BACKGROUND:There are established guidelines for pediatric oncology patients with neutropenic fever. However, half of pediatric oncology patients present with non-neutropenic fever. For this group, no established guidelines exist. OBJECTIVE:In this scoping review, we have explored the outcomes of non-neutropenic fever in pediatric, adolescent, and young adult patients with cancer-directed treatment. The results of this scoping review should assist in the creation of a guideline for the management of non-neutropenic fever in this group of patients. METHODS:Multiple electronic databases and reference lists were searched (PubMed, MEDLINE CENTRAL, and Google (first 100 results only)). Included are retrospective and prospective cohort studies on the management and outcome of pediatric oncology patients with non-neutropenic fever that have been published after the year 2000. RESULTS:Seventeen studies with a total of 10.845 fever episodes were included, that address the treatment and outcome of patients with non-neutropenic fever. The rate of bacteremia was 1.6 - 14.4% (mean 5.8%). The mortality rate was low and due to non-bacterial causes. Across different studies, proposed risk factors for bacteremia were higher temperature, prolonged fever over 72 hours, ill-appearing patients, chills, hypotension, leukocytosis, infancy, and the presence of a Broivac/ Hickman catheter. Limitations to this study are the risk of bias and potential incomplete identification of relevant studies pertinent to the research questions asked. CONCLUSION:Due to significant heterogeneity, the published data so far are not sufficient to propose evidence-based guidelines for pediatric oncology patients with non-neutropenic fever. Prospective, multicenter registries based on uniform definitions are needed. No funding was received for this manuscript.

Invasive fungal diseases (IFDs) cause high morbidity and mortality in children with cancer and hematopoietic cell transplantation (HCT). While international guidelines exist for prevention, diagnosis, and treatment, pediatric-specific evidence remains limited and practices vary. Geographic distribution of the 62 participating pediatric oncology centers First-line and first-line alternative antifungal treatment for candidemia and invasive pulmonary aspergillosis in 62 pediatric oncology centers In Jun-Sep 2024, we surveyed 72 pediatric oncology centers in Germany, Austria, and Switzerland (German Society for Paediatric Oncology and Haematology) using a questionnaire covering center volume, ID expertise, diagnostic tools, prophylaxis protocols, therapeutic drug monitoring (TDM), and treatment pathways for aspergillosis and candidemia. Data were analyzed descriptively; associations between center size, ID resources, and IFD incidence were tested via Mann–Whitney U and linear regression. Sixty-two centers (86% response) participated: 51 DE, 5 AT, 6 CH (Figure 1). Median new oncology cases in 2023 was 56 (IQR 40–75); 55% managed HCT. Proven or probable IFDs were reported by 89% of centers at a median incidence of 4.6% (IQR 3.0–5.9%). A pediatric ID specialist was available in 58% of centers (100% CH, 51% DE, 40% AT); 58% offered formal ID consultation (24% 24/7). Larger centers more often had ID specialists (p=0.008) and maintained antifungal SOPs (p=0.02). All centers performed culture and histopathology; galactomannan testing in 94%, β-D-glucan in 53%, PCR in 86%. In-house TDM for voriconazole was available in 52%, less frequently for posaconazole and isavuconazole. Prophylaxis strategies varied, with liposomal amphotericin B (AMB) used most frequently across risk groups. AMB was the preferred first-line therapy for invasive pulmonary aspergillosis (71% of centers) and candidemia (45%), followed by voriconazole and echinocandin, retrospectively (Figure 2). Heterogeneity exists in IFD management across pediatric oncology centers in the DACH region, influenced by center size and ID resource availability. Gaps include inconsistent SOPs, limited 24/7 ID support, and incomplete access to TDM. Strengthening oncology–ID collaborations, standardizing SOPs, and enhancing antifungal stewardship -potentially via digital platforms- may harmonize care and improve outcomes for children at risk of IFD. Oliver A. Cornely, Prof. Dr., Al-Jazeera Pharmaceuticals/Hikma: Honoraria|Basilea: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Board Member|Cidara: Grant/Research Support|Elion: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|Grupo Biotoscana/United Medical/Knight: Honoraria|Melinta: Advisor/Consultant|Melinta: Board Member|MSD: Honoraria|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Mundipharma: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pulmocide: Board Member|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria Andreas H. Groll, MD, Basilea: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck, Sharp & Dohme: Advisor/Consultant|Mundipharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Honoraria

Abstract In pediatric cancer patients, platinum-induced sensory hearing loss (SHL) manifests in bilateral, symmetrical loss of outer hair cells and starts at a frequency range up to 10 kHz. Hearing loss has a significant impact on education, social integration and personality development in childhood cancer survivors. Early reliable detection of hearing loss may prompt attending oncologists to change chemotherapy if a less ototoxic therapeutic alternative is available. Pediatric cancer patients (2–19 years) receiving cisplatin-, carboplatin- or vincristine-containing regimens were eligible. Ultra-high frequency pure tone audiometry (PTA) and ultra-high frequency DPOAE measurements (up to 16 kHz) were compared. A total of 153 examinations were performed in 83 consecutive patients. While only 60 PTAs yielded reliable results, 153 DPOAE examinations up to 16 kHz were informative. Significant findings were observed between 10 and 16 kHz in both PTA and DPOAE assessments. In the cisplatin group, we found a significant reduction in DPOAE levels from 13 to 16 kHz, as well as a significant increase in DPOAE levels at 2.5 kHz and 3 kHz. Treatment with VCR and carboplatin did not result in substantial SHL. Hearing measurements up to 16 kHz can reveal an early ototoxic effect. In pediatric cancer patients, DPOAE measurement (up to 16 kHz) is more feasible and reliable (compared to PTA) and can detect SHL in ultra-high frequencies (10–16 kHz) at an earlier time point.

Francisella tularensis, the causative agent of tularemia, poses a challenge for diagnosis and treatment due to its diverse clinical presentations and low incidence. Hence, the awareness among clinicians is comparatively low. This study reports the clinical characteristics, diagnostic approaches, and treatment outcomes of tularemia cases at one tertiary center in Germany over a 12-yearperiod.This retrospective monocentric case series considered all tularemia cases diagnosed at Saarland University Medical Center in Homburg, Germany between January 2013 and December 2024. Cases were identified from electronic medical records, and the certainty of tularemia was graded as definite, probable and possible infection, based on results of serology, polymerase chain reaction (PCR) assays, or blood cultures. Clinical data were extracted from patient records and supplemented by follow-up information from the clinicians.We identified 14 tularemia cases, including 6 definite as well as 3 probable and 5 possible cases. The clinical presentation was highly variable, with the (ulcero-)glandular form being the most common entity (10/14). Invasive diagnostics or surgery were required in eleven out of 14 patients. Initial misdiagnosis was common, leading to delayed diagnosis and multiple courses of ineffective antibiotics. Definite treatment included fluoroquinolones or doxycycline, and led to resolution of symptoms in most patients.The varied clinical manifestations of tularemia, from classic (ulcero-)glandular forms to severe and atypical presentations illustrate its diagnostic and clinical complexity. Enhanced awareness and early consideration are crucial, especially in endemic areas or patients with anamnestic environmental exposures.

Background Infections are highly relevant for neonatal mortality and long-term morbidities in survivors. Therefore, it is an urgent need to optimize and evaluate infection prevention and control (IPC) strategies. Several infection outbreaks in German neonatal intensive care units (NICUs) required rapid responses by hospitals and improved future preparedness. As a consequence, German authorities recommended weekly colonization screening on NICUs. This screening aims to detect multidrug-resistant organisms (MDRO) and bacteria with high transmissibility. According to these guidelines, infants colonized with multiresistant gram-negative (MRGN) bacteria with in-vitro resistance to piperacillin and cephalosporins (2MRGN) should be cared wearing non-sterile gloves and gowns in addition to standard hygiene precautions. Whether these extended IPC measures have an individual benefit for infants or contribute to the prevention of infection outbreaks has not yet been scientifically proven. This study aims to evaluate the effect of hand desinfection as compared to hand desinfection + gloves and gowns (barrier care) for the care of 2MRGN colonized infants in NICUs on infection and transmission rates through a multicenter, cluster randomized controlled trial (BALTIC study, Ba rrier protection to l ower t ransmission and i nfection rates with Gram-negative 2-MRGN in preterm c hildren). Methods 12 participating NICUs were randomly allocated to two trial arms: receiving the intervention “standard precautions with a special focus on hand desinfection” or control (standard precautions “plus” barrier care) for the care of 2MRGN positive infants. Cross over was performed after 12 months for another 12 months per site. Primary outcome was the rate of healthcare-associated (HA) Gram-negative bloodstream infections. Secondary outcomes included transmission rate with screening relevant bacteria, overall rate of clinical and culture-proven infections, number of antibiotic cycles and desinfectant use. Regular trainings and hygiene audits are standardized co-interventions. Benchmarking results According to our single center data, 9.3% of NICU-treated infants are colonized with 2MRGN during their hospital stay. BALTIC randomized the first center in October 2020 and finished data collection including close-out monitoring in January 2024. Data analysis will be completed in May 2025. Conclusions BALTIC should contribute to better evidence on the effectiveness of hand desinfection and extended barrier precautions in critically ill newborns. Further benefits include comprehensive multi-center data collection on MDRO colonization dynamics, an improved awareness on IPC strategies and establishment of network platforms including antimicrobial stewardship programs.

Background: The rise of antimicrobial resistance as leading infection-related cause of death will necessitate trans-sectoral efforts on a global level. While many antimicrobial stewardship (AMS) incentives target healthcare workers, addressing undergraduates offers new and hitherto neglected opportunities. Methods: We describe the pilot phase of a novel undergraduate elective (“stewards for future”, SFF) for medical students at the Saarland University, Germany, between 2021 and 2023. We focused on knowledge and attitudes relevant to AMS. To allow for full immersion, we applied case-based learning, problem-based learning, and peer teaching in a small group teaching format spanning 15 hours, including AMS ward rounds. We obtained students’ pre- and post-course self-assessment regarding AMS topics using 5-point Likert scales modified from the previously published ASSURE elective, as well as their subjective experience using the German short intrinsic motivation inventory. Results: Over four terms, 23 undergraduate medical students from the clinical phase participated in the elective. Participants reported an increase in their ability to explain the concept of AMS (mean and standard deviation, pre 3.26±0.94 vs. post 4.74±0.44, p<0.0001), their confidence in choosing the appropriate antibiotic (pre 2.22±0.78 vs. post 3.57±0.58, p<0.0001), their ability to judge potential drug side effects (pre 2.09±0.72 vs. post 3.43±0.71, p<0.0001), their confidence in communicating with colleagues about antibiotics (pre 2.30±0.86 vs. post 3.52±0.83, p<0.0001), their understanding of diagnostics as an AMS tool (pre 4.22±0.41 vs. post 4.91±0.28, p<0.0001), and their ability to evaluate the roles of all AMS team members including their own (pre 2.52±0.77 vs. post 4.13±0.68, p<0.0001). Participants reported having enjoyed the course (4.6±0.5), while they were moderately satisfied with their performance (3.8±1.0). Pressure and anxiety levels were reported to be low (1.8±0.9 and 2.0±1.0 each). Conclusions: Student participants of the elective SFF reported increased competencies relevant to AMS, while enjoying the course format. Sustainability and scalability will ultimately depend on the implementation into the core curriculum.