Ulrich von Both

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. These patients often experience severe, recurrent lower respiratory tract infections (LRTIs). These infections, of both viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Based on expert consensus and newly available data, we have updated the previous 2024 clinical recommendations on the management of LRTIs in children and adolescents with SNI in Germany. This update now also addresses multidrug-resistant organism colonization, respiratory support, discharge planning, and prophylactic strategies. The recommendations emphasize comprehensive multidisciplinary care, antimicrobial stewardship, and a stepwise, risk-stratified approach to antibiotic therapy. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, secretion management, and respiratory as well as cough support. In suspected bacterial LRTIs, antibiotic treatment (ABT) should be guided by clinical severity, previous microbiological findings, and treatment response, with an aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam reserved for selected high-risk patients. Ongoing management includes regular reassessment, adjustment of ABT based on pathogen identification, and optimization of supportive care. Conclusion : The updated recommendations provide a practical, multidisciplinary framework for the inpatient management of LRTIs in children and adolescents with SNI, combining optimized supportive care with antimicrobial stewardship and a stepwise, risk-stratified approach to antibiotic treatment. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTI) • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population • The frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens What is New: • Compared with the 2024 recommendations, this update provides more detailed guidance on secretion management and respiratory and cough support, introduces explicit discharge criteria, and expands decision-making for patients colonized with multidrug-resistant organisms. The antibiotic strategy has been further specified regarding broad-spectrum antibiotic therapy, while preventive recommendations have been expanded and updated.

Background: Mycoplasma pneumoniae (MPP) infections occur regularly every 1 to 3 years. A wave of infections was anticipated around late 2022 to early 2023. However, our data revealed a delayed onset, with a notable increase in cases in 2023/24. This study describes pediatric MPP detections during this resurgence and explores clinical differences between MPP mono-detection and MPP with rhinovirus/enterovirus (RV/EV) co-detection. Methods: We retrospectively analyzed PCR-confirmed MPP detections in children aged 0–17 years presenting to a tertiary pediatric hospital between 2017 and 2024. Cases from 2017 to 2022 were used as descriptive historical background data (G1, n = 10), while the main analysis focused on the 2023/24 cohort (G2, n = 87). Within this cohort, children with MPP mono-detection were compared with those with MPP plus RV/EV co-detection. Group comparisons were performed using chi-square or Fisher’s exact test and t-test or Mann–Whitney U test, as appropriate. Results: Ten sporadic MPP detections occurred between 2017 and 2022, compared with 87 detections in 2023/24, indicating a marked increase in hospital presentations. Because of the small historical group, comparisons with 2023/24 were interpreted descriptively. In the 2023/24 cohort, RV/EV was the most frequent viral co-detection. Compared with children with MPP mono-detection, children with MPP plus RV/EV co-detection were more often male, were less frequently febrile, and showed lower inflammatory parameters, including lower rates of elevated CRP and higher rates of leukopenia and neutropenia. Conclusion: In 2023/24, Mycoplasma pneumoniae infections surged dramatically, accompanied by an unprecedented rise in Rhino/Enterovirus coinfections especially in young, male patients. While these findings highlight a potentially important phenotypic pattern, further prospective studies are needed to clarify causality, temporal sequence, and distinct underlying mechanisms.

Transcriptomic analyses reveal the status of cells, tissues, or organisms, across states of health and disease. RNA velocity adds a temporal dimension to single cell analyses, predicting future transcriptomic and phenotypic states, based on the current spliced and unspliced mRNA of each cell. We hypothesized that RNA velocity could be adapted to predict future clinical state of individuals with acute and chronic illnesses, using their whole-blood transcriptomes. We developed VeloCD, a method for quantitative prediction of transitions in clinical state from a single time-point RNA sample. This predicts transcriptomic trajectories and future infection status in influenza A and SARS-CoV-2 controlled human infection studies, which are consistent with trajectories in naturally acquired infections. In HIV-TB coinfected individuals, VeloCD predicts the onset of immune reconstitution inflammatory syndrome. In individuals receiving biological therapy for inflammatory bowel disease, whole blood RNA velocity after the first dose of treatment indicates whether remission will be achieved by the end of the treatment course. In a multinational observational study of acutely unwell febrile children, VeloCD predicts those with greatest medical care requirements. Our results demonstrate proof-of-concept for the use of RNA velocity to predict trajectories of human diseases.