Background:Cancer registries are essential to monitor cancer incidence and survival to provide better quality cancer data for research. In Switzerland, the pediatric oncology units within pediatric hospitals actively report cancer cases, and the coding and registration team of the Childhood Cancer Registry (ChCR) enters data manually from medical files into the registry database. There are no automated data transfers or feedback loops between the pediatric oncology clinics and the ChCR. This ongoing process is time-consuming, inefficient, and a source of potential errors. Objective:SwissPedCancer aims to explore the options for automated data transfers from clinical data warehouses and feedback loops to make cancer registry processes more efficient. Methods:SwissPedCancer is a nested project within the national data stream initiative, the Swiss Pediatric Personalized Research Network (SwissPedHealth). Since September 2022, SwissPedHealth has developed and piloted structures to make routine clinical data from pediatric oncology clinics available for monitoring, benchmarking, and research in an interoperable, standardized, and quality-controlled way. SwissPedCancer expects to include approximately 2800 patients diagnosed with cancer before the age of 20 years between 2017 and 2023. The pediatric oncology clinics' data and the manually validated ChCR data will be delivered separately to a secure national computing network for health-related data (Biomedical Information Technology). We will compare these two data sources to assess completeness (case ascertainment), accuracy (validity), and timeliness of cancer registration in the ChCR. We will evaluate data on diagnosis, treatments, underlying genetic disease, remission, relapse, and late effects. SwissPedCancer will provide a framework for optimizing standardized and uniform data transfers between pediatric oncology clinics and the ChCR and for other registries within Switzerland. Results:The project was funded in September 2022 and received ethics exemption in October 2023. Data extraction from participating hospitals and the ChCR is expected to commence in January 2026. Study results are anticipated to be available in summer 2026. Conclusions:SwissPedCancer aims to reduce manual workload while improving the completeness, accuracy, timeliness, and comparability of childhood cancer data in Switzerland. The project will contribute to a robust, interoperable, and sustainable national infrastructure supporting high-quality cancer registration, timely analyses, and evidence-based decision-making.

OBJECTIVE: Anthropometric data are critical in paediatric care, routinely assessed during clinical visits, and available in electronic health records (EHRs). We describe the feasibility of extracting anthropometric data from heterogeneous EHR systems of Swiss childrens hospitals, evaluate their availability and quality, and assess the cohorts representativeness of the general population. METHODS: In this multicentre study (SwissPedGrowth), we retrospectively collected EHRs from patients <20 years who visited hospitals in Basel, Bern, Geneva, Lausanne, Luzern, St. Gallen, or Zurich between 2017-2023. Sociodemographic, administrative, and clinical information from EHRs were provided in a standardized way by a paediatric national data stream (SwissPedHealth), including the Swiss Neighbourhood Index of Socioeconomic Position (Swiss-SEP). We counted anthropometric recordings per visit to describe availability and used a self-developed and an existing (growthcleanr) algorithm to investigate data quality. To assess representativeness, we compared sociodemographic characteristics between SwissPedGrowth and the general paediatric population in Switzerland, computed standardized differences (effect size: 0.2 small, 0.5 medium, 0.8 large), and weighted the study population to reduce differences. RESULTS: We included 477,531 patients and 2,171,633 hospital visits; 54% boys, 71% Swiss, mean Swiss-SEP 65 (SD: 11), and median age at visit 6.3 [IQR: 2.3, 11.8] years. Height recordings were available for 20% of the visits, weights for 43%, and head circumferences for 5%, with better availability for inpatient stays than outpatient or emergency visits. Combining the self-developed and existing algorithm, 4% of heights and 3% of weights were flagged as outliers and 29% of heights and 31% of weights as carried forward from previous visits or same day duplicates. Sociodemographic differences between SwissPedGrowth and the general population were small or small-to-medium and disappeared after weighting. CONCLUSION: SwissPedGrowth demonstrates feasibility of extracting high-quality anthropometric data for paediatric growth research, but challenges regarding completeness and harmonization of EHR data across Swiss hospitals remain. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported through the grant NDS-2021-911 (SwissPedHealth) from the Swiss Personalized Health Network (SPHN) and the Strategic Focal Area Personalized Health and Related Technologies (PHRT) of the ETH Domain (Swiss Federal Institutes of Technology). The funders had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: SwissPedGrowth was approved by the cantonal ethics commission Bern (Kantonale Ethikkomission Bern 2023-00022) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data may be made available to investigators upon request by email to the corresponding author.

Objectives The aim of this study is to evaluate existing evidence on the effectiveness of amoxicillin and amoxicillin-clavulanate for community-acquired pneumonia in children and adults.Design Systematic review and meta-analysis.Data sources PubMed, Cochrane Library, Web of Science and Ovid-MEDLINER were searched with no language restrictions through 16 July 2024.Eligibility criteria We included studies comparing the effectiveness of amoxicillin or amoxicillin-clavulanate versus other antibiotics or placebo.Data extraction and synthesis Only randomised controlled trials comparing amoxicillin or amoxicillin-clavulanate with another antibiotic or placebo with a primary outcome of clinical resolution or clinical failure were eligible for our review. We used random-effects and fixed-effects logistic regression models to estimate the pooled treatment effect size. Heterogeneity of the studies was evaluated using the τ statistic. We performed an unplanned frequentist random-effects network meta-analysis for the indirect comparison between amoxicillin and amoxicillin-clavulanate. The revised Cochrane risk of bias tool for randomised trials was used to assess and categorise studies into low risk of bias, some concerns or high risk of bias.Results We extracted data from 44 studies including 45 400 patients. We found no evidence of a differential effect on clinical resolution when comparing amoxicillin with other antibiotics (n=15 trials; pooled OR 0.88; 95% CI 0.56 to 1.38, where >1 favours amoxicillin) or amoxicillin-clavulanate with other antibiotics (n=17; OR 0.89; 95% CI 0.76 to 1.04). Similarly, evidence of difference in clinical failure between amoxicillin and other antibiotics was unclear and unable to rule out clinically important benefits or harms (n=8; OR 0.76; 95% CI 0.55 to 1.06, where <1 favours amoxicillin). We found no evidence of a differential effect on clinical resolution between adults treated with amoxicillin and amoxicillin-clavulanate (n=28; OR 1.04; 95% CI 0.64 to 1.70, where >1 favours amoxicillin-clavulanate). Sixty-three per cent and 29% of amoxicillin and amoxicillin-clavulanate studies, respectively, had low risk of bias according to the Cochrane risk of bias tool for randomised trials.Conclusions Current evidence is unclear as to whether amoxicillin or amoxicillin-clavulanate differs from other antibiotics, or from each other, in the treatment of community-acquired pneumonia, owing to the small number of trials and substantial heterogeneity in comparators used across study settings.PROSPERO registration number CRD42024568554.

Kangaroo Care (KC) is an evidence-based intervention, with greatest benefit when initiated early and provided for continuous periods, as recommended by the World Health Organization. However, uncertainty remains around KC operationalisation in research settings and how this may influence subsequent implementation in routine practice. We conducted a narrative synthesis of KC intervention characteristics reported in randomised controlled trials (RCTs), based on a prior systematic review and meta-analysis. We focused on elements relevant to implementation, including instructions for delivery, recommended equipment or environment, initiation timing, duration of skin-to-skin contact, and contraindications. Our synthesis shows that, even within RCTs, KC is frequently not delivered in line with WHO recommendations with respect to initiation timing, duration, and eligibility. This contributes to uncertainty in clinical target setting and reflects an implementation gap that mirrors challenges observed in routine care. Commonly reported barriers included infrastructural constraints, staffing and training requirements, and cultural factors influencing caregiver participation. These findings highlight that evidence of KC effectiveness alone is insufficient to ensure optimal delivery in practice. Implementation studies conducted in real-life settings are needed to determine whether observed benefits translate into routine care and to identify strategies that support timely initiation, sufficient duration, and sustained KC provision. IMPACT: Key intervention characteristics of Kangaroo Care (KC), such as instructions, environment, initiation timing, duration, and contraindications that are often insufficiently reported in randomised controlled trials, but critical for implementation. Even in RCTs, KC is frequently not delivered in accordance with WHO recommendations, highlighting uncertainty in clinical target setting and revealing an implementation gap that extends beyond routine clinical practice into research settings. By identifying recurring infrastructural, personnel, and cultural barriers across trials, this work informs the design of real-world effectiveness and implementation studies, including the ongoing NeoDeco effectiveness-implementation trial.

ABSTRACT BACKGROUND We used anthropometric data from electronic health records (EHRs) of Swiss children’s hospitals to evaluate growth references and estimate centile curves. METHODS We received EHRs extracted from seven Swiss children’s hospitals and analysed two samples: all children with a height, weight, body mass index (BMI), or head circumference recording, and a subsample restricted to children without diseases potentially affecting growth, weighted to represent the general population. We calculated mean z-scores based on the World Health Organization growth references adopted for Switzerland in 2011 (CH-WHO 2011) and current Swiss growth references (Swiss 2026). We estimated sex-specific centile curves in the subsample using generalised additive models for location, scale, and shape. RESULTS We included 213,868 children with height, 448,002 with weight, 209,244 with BMI, and 67,397 with head circumference recordings. Mean z-scores in the ‘all children’ sample were (CH- WHO 2011; Swiss 2026): height (0.10; -0.19), weight (0.16; -0.09), BMI (0.04; -0.07), head circumference (-0.28, -0.28); and in the subsample: height (0.34; 0.00), weight (0.27; 0.01), BMI (0.18; 0.05), and head circumference (0.04; 0.01). The 50 th height, weight, BMI, and head circumference centiles of girls and boys in the subsample closely followed those of Swiss 2026, with slightly wider 3 rd and 97 th centiles in infancy and adolescence. CONCLUSION Height, weight, BMI, and head circumference centiles aligned well with the Swiss 2026 growth references in Switzerland, demonstrating that hospital EHRs could contribute to future growth references.

THE GOOD, THE BAD, THE UGLY IN BACTERIAL COLONIZATION After leaving the uterus, a neonate immediately encounters a vast world of microbes and begins developing its own microbiota on all exposed body sites and surfaces. Bacterial colonization on the body surface after birth is characterized by a great diversity of microorganisms in which "good" bacteria (eg, Staphylococcus epidermidis, etc) prevent "bad" bacteria (eg, Staphylococcus aureus (S. aureus)) from taking a foothold and potentially going on to cause infection ("the ugly") (of course, this dichotomy does not sufficiently reflect the complex reality of the colonization—infection continuum and pathogenic potential is not exclusively determined by the bacterium itself, but results from a complex array of pathogen–host interactions). Newborns pick up bacteria from the mother, other family members, environment and even pets with infants born at term being readily prepared for microbial interactions. But what happens in preterm neonates with their numerous limitations to adequately incorporate even "good" bacteria into their microbiota and to limit the uncontrolled systemic spread of "bad" bacteria? THE RULES OF COLONIZATION: THE CASE OF S. AUREUS Low birthweight and very preterm neonates, particularly with repeated or prolonged antibiotic administration and long hospital stays, have a higher risk for colonization (and infection) with S. aureus. In a monocentric study with mainly preterm neonates in a non-outbreak setting in Germany, 23% became colonized at some point with S. aureus during their neonatal intensive care unit (NICU) stay.1 Of note, the rate of colonized babies was higher among preterm (26.2%) than in term neonates (8.8%), albeit the latter only composed a small proportion of study participants. Thus, the results may not be representative of healthy term babies, and epidemiology may vary depending on geographical backgrounds. Overall, it took a median of 17 days (interquartile range 11–37 days) to first detection of S. aureus in this study. Low birth weight and longer length of hospital stay were independently associated with higher rates of colonization.1 Similarly, a recent systematic review and meta-analysis for methicillin-resistant Staphylococcus aureus (MRSA) showed that very preterm neonates (gestational age <32 weeks) and very-low birth weight infants (<1500 g) are an important risk group for MRSA colonization.2 There are at least 3 transmission pathways for bacterial colonization in neonatal care: transmission via parents, via healthcare workers (HCWs) and via the patient environment. First, in a study investigating S. aureus transmission between parents and their infants in an intensive care setting, 74 of 190 infants (38.9%) were colonized with S. aureus by 90 days. Furthermore, 42 of 74 (56.8%) had a strain concordant with the parental baseline strain, indicating transmission via the parents.3 Second, HCWs contribute to S. aureus transmission in the NICU setting, as outbreak reports show,4 while data for the nonoutbreak setting are limited and colonization rates among HCWs are rarely assessed. Nevertheless, the NICU setting with its long hospitalization duration and the intimate contact between HCW and neonate in patient care facilitates HCW-to-patient transmissions (no "yuck factor"). Third, transmission via the patient environment is another pathway for bacterial colonization in hospitalized neonates as S. aureus is easily transmitted via hands, surfaces, and fomites. Considering these different pathways of transmission, preventing colonization with S. aureus in neonates usually entails several multimodal strategies, including general infection prevention/control (IPC) interventions (hand hygiene, contact precautions, patient isolation), environmental interventions (cleaning, dedicated equipment), HCW-targeted interventions (staff cohorting or screening), active surveillance and patient decolonization.5 WHO SHOULD BE DECOLONIZED? Given multiple sources of colonization and disregarding indirect environmental sources, it is unclear who might be the most optimal target for decolonization. Parental decolonization may be the most effective measure (to prevent colonization with the parental strain, but not all S. aureus strains), especially in the context of increasing delivery of family-centered care. A randomized controlled trial investigating the effect of parental S. aureus decolonization on transmission of S. aureus to their infants showed that only 13 of 89 neonates (14.6%) were colonized with a concordant S. aureus strain [risk difference, −14.1% (95% confidence interval (CI): −30.8% to −3.9%)], compared with 29 of 101 neonates (28.7%), in which parents did not apply decolonization measures (intranasal mupirocin and 2% chlorhexidine-impregnated cloths for 5 days).3 In an outbreak setting, identifying a colonized source, for example, among front-line clinical staff, with a targeted screening and decolonization strategy may also prove successful.4 DECOLONIZE BOTH MSSA AND MRSA? Much of the evidence generated by transmission and IPC studies regarding colonization/decolonization traditionally centered on MRSA. However, regarding its pathogenic potential itself and infection rates, MSSA is a comparable risk factor for consecutive infection, morbidity and mortality in neonates.6 Consequently, most recent IPC guidelines cover both pathogens in their recommendations.5 CAN NEONATES BE DECOLONIZED AT ALL? Strategies to permanently decolonize especially preterm neonates from MRSA, but also MSSA, show great variability, poor success and lack a solid evidence base,7 especially as a stand-alone IPC measure. A common trunk is the application of nasal mupirocin ointment8 (sometimes also applied to the umbilicus and wounds, see 9) with or without whole body washing with antiseptics active against S. aureus (chlorhexidine gluconate10 or octenidine dihydrochloride 0.1%11) on several consecutive days with varying recommendations for duration. This has some practical challenges related to neonates being obligate nose-breathers and avoidance of hypothermia. The effectiveness and duration of decolonization may be limited by the ubiquitous sources and pathways for recolonization outlined above and the occurrence of infections before colonized neonates are being identified as carriers, leaving decolonization as a reactive and short-term intervention with limited success (compare 8,9). DECOLONIZATION OF BACTERIA OTHER THAN S. AUREUS Skin decolonization with different antiseptics has been investigated in preterm and term neonates to reduce bacterial skin colonization density (and possible consecutive healthcare-associated infections) of bacteria other than S. aureus.12 Another strategy, selective digestive decontamination in critically ill children including neonates, has been discussed in the literature to reduce nosocomial infections caused by microorganisms residing in the oral cavity and gastrointestinal tract.13,14 However, this strategy has not been established as a standard IPC strategy given concerns around short- and long-term side effects of the applied antibiotics and issues around antibiotic resistance and microbiota alterations. NEW FRONTIERS Failure rates in decolonization and high recolonization rates with S. aureus have led to innovative clinical trials investigating maternal/parental skin-to-skin contact ("kangaroo care," "bonding") as an intervention. In a recent study, the decolonization rate in MRSA colonized newborns was increased in the interventional, skin-to-skin group (risk ratio = 2.27; 95% CI: 1.27–4.07; P = 0.003) with a low number needed to treat of 4.0 (95% CI: 2.2–9.4).15 A European-wide cluster-randomized controlled trial ("NeoIPC/NeoDeco", NCT05993442) is currently testing "optimized kangaroo care" as IPC intervention to reduce severe neonatal infection and resistant bacterial colonization. Similarly, microbiota transfer of nonparental bacterial skin strains also seems a potentially promising strategy to use the mechanism of "bacterial interference," suppressing colonization with "bad" bacteria16 and increasing skin microbiota balance towards diversity. However, evidence is currently lacking on what species this bacterial "cocktail" should include and in what concentrations and composition. Furthermore, it is unclear which neonates at what time during their NICU stay would benefit the most and under which circrumstances this approach outweighs the potential risks of systemic infections and uncontrolled spread.16 Overall, this changing view on colonization/decolonization in hospitalized neonates entails a paradigm shift from conceptualizing the skin of neonates as an area where bacteria causative of dysbiosis need to be eliminated—toward an understanding of balancing the neonatal bacterial skin microbiota by adding conducive bacteria and increasing the degree of diversity (Fig. 1) (see also 16). In other fields of clinical microbiology, this concept has been termed as "microbial management" which entails strategies to modulate and curate diverse microbial environments.17 Hospitalized neonates in the NICU are unusual in that they initially have a limited microbiota of their own and are therefore at risk of acquiring a hospital-based microbiota, which differs greatly from the microbiota of newborns co-admitted with mothers on the postnatal ward and promptly discharged home.FIGURE 1.: "Decolonization" vs. "balancing colonization" paradigms in hospitalized neonates.At least 2 paradigms can be identified in the literature as to whether "bad" bacteria need to be eliminated on the skin of hospitalized neonates ("decolonization paradigm"), or whether the skin microbiota needs to be balanced by introducing "good" bacteria ("balancing colonization paradigm"). Decolonizing may take place as application of antiseptic/antibacterial substances resulting in a less diverse population of bacteria ("bacterial diversity") on the neonate's skin. The "balancing colonization" approach may entail "kangaroo care" and results in a higher degree of bacterial diversity on the neonate's skin. Created in BioRender. Bielicki, J. (2025) https://BioRender.com/t18v567Further research is needed to determine the strengths and limitations of parental and nonparental bacterial transfer, for example, via kangaroo care, to micromanage the neonatal skin microbiota toward a diverse and healthy composition with protective features against infections and potentially reducing detrimental bacterial colonization. Even in settings with low prevalence of multidrug-resistant organisms, the microbiota of NICU-hospitalized infants are likely to substantially diverge from what would be considered healthy. Interventions based on the concept of "microbial management" rather than aiming at decolonization may therefore be the most promising and relevant to many high-risk infants globally and deserve to be studied further. Furthermore, baseline surveillance data of multidrug-resistant organism rates is country-specific, differ greatly between different world regions and may limit clinically meaningful application of microbial management strategies in neonates or might entail a greater need for screening and monitoring. ACKNOWLEDGMENTS The authors thank Steffen Engelhart for the critical discussion during manuscript drafting.

S, I AND R CATEGORIES FOR INTERPRETATION OF SUSCEPTIBILITY TESTING RESULTS In addition to its work on standardizing and improving the validity of methods for antimicrobial susceptibility testing (AST), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) issues yearly updates on its guidance to interpret the results of these tests. Interpretation of test results generally falls into 3 categories. In 2019, EUCAST updated the definitions for the 3 categories as follows: S: Susceptible, standard dosing regimen: a microorganism is categorized as "Susceptible, standard dosing regimen," when there is a high likelihood of therapeutic success using a standard dosing regimen of the agent. I: Susceptible, increased exposure: A microorganism is categorized as "Susceptible, Increased exposure" when there is a high likelihood of therapeutic success if exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection. R: Resistant: A microorganism is categorized as "Resistant" when there is a high likelihood of therapeutic failure even when there is increased exposure. Exposure in the "I" category was defined as "a function of how the mode of administration, dose, dosing interval, infusion time, as well as distribution and excretion of the antimicrobial agent will influence the infecting organism at the site of infection."1 Similar definitions were not adopted by the other globally leading institution offering AST guidelines [the Clinical and Laboratory Standards Institute (CLSI)] although CLSI introduced the "susceptible dose-dependent" subcategory of "I" otherwise defined as "intermediate" in 2014.2 Currently, "I" may, therefore, be read as "intermediate," according to CLSI, or as "susceptible, increased exposure," according to EUCAST, and it is becoming arguably more important for clinicians to understand which testing and interpretation standards their laboratory uses. CLSI's "I" category still subsumes a variety of scenarios in which the susceptibility of a tested microorganism may remain uncertain due to drug levels at the site of infection, or due to difficulties in interpreting test results—generally results in the "area of technical uncertainty.2" Due to this uncertainty, the conservative approach clinicians generally adopt when approaching the CLSI "intermediate" category is to regard it as likely resistant to the tested antibiotic agent. With the 2019 introduction of the "susceptible, increased exposure" category, EUCAST requires a change of this approach to now regarding isolates tested as "I" for a certain antibiotic agent as susceptible to it, with the additional consideration that the antibiotic necessarily needs to achieve sufficient exposure. Guidance as to how dosing of an antibiotic is considered to influence this is published by EUCAST for adults,3 with a parallel dosing table for children currently being in development.4 TRANSLATION OF TEST RESULTS INTO SUSCEPTIBILITY CATEGORIES: CLINICAL BREAKPOINTS Both EUCAST and CLSI publish tables of clinical breakpoints that offer guidance on how test results translate into the categories above. Broadly, breakpoints are thresholds for either minimum inhibitory concentrations (MICs) or growth-free zone diameters that separate results falling into different categories. Breakpoint setting makes use of various factors, including distribution of test results in previously documented isolates of bacteria, experiences (mainly findings from clinical studies) about outcomes of patients infected with bacteria with different AST test results and expected drug levels at the site of infection. The integration of these factors results in specific breakpoints for the combination of 1 bacterial species or group (eg, Enterobacteriaceae) and 1 antibacterial agent. Breakpoints may be set differently according to the site of infection, but they do not take into consideration if an isolate has been obtained from a pediatric or adult patient. EUCAST's updated definition means that the previously common sequence of interpretations moving from "S" via "I" to "R" with gradually increasing MICs or decreasing zone diameters no longer applies. For each combination of bacterium and agent, susceptible will either be "S" or "I," depending on whether exposure and, by consequence, dosing are heightened concerns. AST results for Pseudomonas aeruginosa (as a common example) isolates not showing unusually high MICs to any antibiotic will now, nonetheless, show "I" for most reported agents, indicating that these agents should always be given at high doses when treating Pseudomonas spp. Consequently, there is only 1 breakpoint separating "R" from either "S" or "I." SHOULD "S," "I" AND "R" BREAKPOINTS EQUALLY BE APPLIED TO ISOLATES FROM PEDIATRIC PATIENTS? The meaning of the AST results applying the EUCAST "S," "I" and "R" categories is not affected by the host from whom the bacterium was isolated. An alternative antibiotic can be selected if an isolate has been tested as "R," or dosing can be increased above the standard if an isolate is reported as "I." Seeing that EUCAST uses the same breakpoints for isolates from adults and children, the relevant question is if these are transferrable across patient age groups. Regarding the contributing factors for breakpoint setting, this would require (1) the circulating bacterial populations in both patient populations to be similar, (2) outcomes of patients infected with bacteria with similar AST results also to be similar and (3) expected drug levels at the site of infection to be similar. The pool of bacterial isolates that is available to describe the distribution of antibiotic concentrations able to inhibit growth (MIC) and, thereby, determine which MICs will be regarded as elevated is not equally representative for different patient age groups. The contribution of different age groups depends both on how commonly an age group is sampled and on how prevalent bacteria are in this age group. As an example, Escherichia coli is commonly found in urinary tract infections in elderly patients and adult women. Even when restricting the pool to bloodstream isolates, population-based studies suggest that about 20× and 200× more E. coli isolates will be derived from people over 75 alone than from infants under the age of 1 year and adolescents between 10 and 14 years, respectively.5 Isolates of E. coli from pediatric patients only make a very minor contribution to the previously tested bacterial population. Using 1 overall distribution of MICs to determine where elevated MICs start relies on the assumption that bacterial populations in different patient groups are all part of a single homogenous bacterial population colonizing and infecting humans. While this may be true for some bacterial species, heavily age-dependent patterns of interpersonal close contacts make it seem possible that age group-specific subpopulations may arise and be maintained.6 While patient outcome by MIC is not a frequently used endpoint in clinical studies, a limited number of studies in pediatric patients have shown an increase in adverse outcomes with higher MICs below the clinical breakpoint, that is, when the isolate would still have been classified within the "S" category.7 Although this may be indicative of the breakpoint not being appropriate for children, similar findings for Gram-negative bacteria have been reported in adults.8 This illustrates that independent of age, the category of "susceptible" still requires careful patient monitoring, especially in the treatment of more critical infections. Antibiotic drug levels at the site of infection are a function of dosing (dose and dosing interval), mode of administration (eg, oral, i.m., i.v. push, intermittent or continuous i.v. infusion) and physiologically determined pharmacokinetic processes. All of these differ substantially between pediatric and adult patients but also between age groups within the pediatric and adult populations. Currently, the breakpoint setting process is not based on common pediatric dosing regimens of antibiotics and does not take different pharmacokinetics in children and neonates into account. Maturation, and body weight and composition result in different distribution and clearance of antibiotics at different pediatric ages.9 Moreover, existing pediatric dosing recommendations for antibiotics differ widely.10 EUCAST's "I" category places a heavy focus on adequate dosing. At the same time, dosing is the main concern regarding the applicability of current clinical breakpoints for pediatric patients. In the absence of harmonized dosing recommendations for pediatrics, and of consideration of these and pediatric pharmacokinetics in breakpoint setting, the "I" category poses a challenge for the selection of an appropriate dosing strategy for the patient in question. CONCLUSIONS AND RECOMMENDATIONS While the "S," "I" and "R" categories are generally applicable to pediatrics, appropriate dosing is the main concern, especially where constellations of "susceptible, increased exposure" (EUCAST's "new I") are targeted. Dosing toward the upper end of accepted ranges should be considered where dose-dependent toxicity is of limited concern. Especially for beta-lactam antibiotics, shorter dosing intervals or extended infusion times may be necessary when managing difficult-to-treat infections. More pharmacokinetic studies will be necessary, especially in neonates and critically ill children, to reduce uncertainty regarding adequate dosing. In line with the definitions, both "susceptible" categories (S and I) only indicate a high probability of success and do not guarantee it. Especially in critical infections, close monitoring of possible treatment failure is advisable.

Bacterial infections are still a main cause of death in children younger than 5 years, yet few age-appropriate antibiotic formulations exist, which limits treatment options and compromises quality of care. In 2023, theWorld Health Organization (WHO) published its first list of priority paediatric antibiotic formulations to guide research and development for age-appropriate antibiotic formulations. Both azithromycin and nitrofurantoin are on this list. Currently, no dispersible tablets are approved or available for these drugs and existing liquid forms are poorly palatable and/or contain excipients of safety concern. To support the development of age-appropriate formulations for these two antibiotics, we produced target product profiles using WHO's methods. For azithromycin, the optimum age-appropriate formulation and dose is scored 100 mg dispersible tablets or an orodispersible 50 mg multiparticulate formulation, with dispersible 50 mg tablets as the minimum requirement. For nitrofurantoin, the optimum age-appropriate formulation is an orodispersible multiparticulate formulation or scored dispersible tablets, with dispersible tablets as the minimum requirement. Based on the WHO recommended dosage of4 mg/kg per day for children for nitrofurantoin, the optimum unit dose is 5 mg. If scoring is feasible, a 10 mg unit dose should be developed for dosing flexibility across paediatric age groups.These profiles aim to support regulatory authorities, pharmaceutical developers, health programmes and other stakeholders in advancing safer, effective and child-appropriate antibiotic formulations.

Background: Children (6–24 kg) with lower respiratory tract infections were prospectively recruited in emergency departments to high or low doses of oral amoxicillin. We identified children who met the criteria for medium and high risks of sepsis, as per the UK’s National Institute for Health and Care Excellence (NICE). Of those able to be discharged with oral antibiotics; 54% (318/591) had high-risk sepsis criteria. NICE sepsis guidance is poorly specific, with implications for antimicrobial resistance and iatrogenic patient harm. Methods: Children (6–24 kg) with lower respiratory tract infections were prospectively recruited in emergency departments to high or low doses of oral amoxicillin. Results: Of those able to be discharged with oral antibiotics, 54% (318/591) had high-risk sepsis criteria as per the UK’s NICE. Conclusions: NICE sepsis guidance is poorly specific, with implications for antimicrobial resistance and iatrogenic patient harm.

K. oxytoca generally has a benign susceptibility profile and low virulence but can cause invasive infections in vulnerable populations, like preterm infants. We aim to describe how whole-genome sequencing (WGS) was used to inform management of a prolonged K. oxytoca outbreak on a neonatal intensive care unit (NICU) and implications for outbreak response involving similar organisms. We retrospectively reviewed outbreak-associated clinical and environmental isolates from a Swiss NICU. WGS was used to track evolution of resistance and highlighted multiple concurrent outbreaks. WGS was performed using a MiSeq or NextSeq 500 Illumina sequencer. The resulting genome sequences were analysed using Ridom SeqSphere. The current report conforms to ORION reporting guidelines. Of 152 Klebsiella spp. patient-derived isolates, 83 were genotyped using WGS, along with six environmental isolates. This confirmed two outbreak waves (November 2021-February 2022, ST18 wildtype; July 2022-June 2023, main cluster ST18 KI β-lactamase hyperproducer), with multiple genotypically connected clusters during the second wave. Confirmed sepsis (K. oxytoca ST18 wildtype) occurred in four preterm or low birthweight infants. Twins presented a genotypically identical ST with a different susceptibility phenotype (ST18 wildtype vs. K1 OXY-hyperproducer). WGS combined with epidemiological investigation and environmental sampling identified an environmental source. There was a second outbreak wave after source removal, presumably due to the prolonged presence of colonised infants with typically long NICU stays and insufficient standard infection prevention and control measures to prevent transmission. WGS use in NICU outbreaks involving low-virulence bacteria can support identification and removal of potentiating environmental sources. These measures, however, will often be insufficient to contain the outbreak, and ongoing WGS surveillance of ubiquitous species may uncover multiple concurrent outbreaks, presumably driven by continuing transfer-transmission between different sources and infants in the NICU. Maximising standard infection prevention and control (IPC) measures is appropriate in this context.

The emergence of SARS-CoV-2 and the implementation of non-pharmaceutical interventions (NPIs) profoundly disrupted the transmission dynamics of respiratory viruses, altering their epidemiology and seasonality. However, comprehensive long-term data on these shifts and their post-pandemic implications remain limited. This study analyzed syndromic multiplex panel testing data from 83'823 respiratory specimens collected from 56,519 patients with respiratory tract infections (RTIs) at two tertiary care centers in northwestern Switzerland to systematically assess changes in respiratory virus circulation, seasonality, age distribution, and disease burden across pre-pandemic (2010-2019), pandemic (2019-2022), and post-pandemic (2022-2024) periods. Pre-pandemic, influenza virus (IV), respiratory syncytial virus (RSV), human coronavirus (HCoV), human metapneumovirus (hMPV), and human parainfluenza virus (HPIV) followed distinct seasonal patterns. During the pandemic, SARS-CoV-2 replaced these viruses, leading to a 70-90% decline in their activity (p < 0.001), while rhinovirus/enterovirus and adenovirus were less affected. After NPIs were lifted, substantial off-season activity with markedly higher case numbers and more hospitalizations, especially among pediatric patients, occurred for IV-A/B, RSV, and atypical bacteria. In post pandemic years, virus-specific seasonality is rebounding, with patterns resembling those seen pre-pandemic. However, higher case numbers, increased hospitalizations, and sustained shifts in age distribution persist. The COVID-19 panemic significantly impacted the etiology, seasonality, and age distribution of RTIs. As NPIs were eased, susceptibility to RTIs, particularly among pediatric patients, increased, resulting in more hospitalizations. While post-pandemic periods show a return to pre-pandemic activity patterns, ongoing monitoring is essential to anticipate shifts in respiratory virus dynamics as immunity levels and virus characteristics evolve.

Recent advancements in nanomechanical microcantilever biosensors open new possibilities for clinical applications, permitting precise analysis of molecular interactions. The technology enables tracking gene expression, molecular conformational changes, antibody binding and antibiotic resistance. In particular, hybridization of DNA or RNA extracted from biopsies and whole blood from patients has led to significant advancements in diagnostics of critical medical conditions, e.g., cancer, bacteraemia and sepsis, utilizing rapid, sensitive, and label-free detection. Direct diagnosis from patient samples is a decisive advantage over competitive methods circumventing elaborate and time-consuming purification, amplification and cultivation procedures prior to analysis. Here, recent developments are presented from simple DNA hybridization of synthesized oligonucleotides to RNA material obtained from patients’ blood samples, highlighting technological advancements in diagnostic applications, such as detection of pathogens and disease biomarkers. We envisage our method to be a significant input to rapid, early and sensitive diagnosis directly from patients’ blood without requirements for amplification or cultivation. This would represent a paradigm shift in diagnostics, as no competing method currently exists.

Adverse event (AE) collection is a key part of evidence generation in clinical trials and an integral element of safety reporting. AE assessment and documentation is particularly challenging in neonates who are a heterogeneous population with high rates of co-morbidities. Neonatal research is finally gaining the attention of regulators regarding drug development and the need for optimal dosing specific to this population. However, further efforts are necessary to ensure that adverse events (AEs) are adequately collected, allowing for the generation of essential safety data. It is also crucial that the methodology used aligns with the intended trial outcomes to minimise the burden on trial sites. In resource-constrained settings, where pharmacovigilance implementation can be particularly challenging, a pragmatic approach to safety reporting is even more important given the significant public health need for effective drugs. This commentary reflects on some of the challenges and potential areas of improvement in safety reporting that could be addressed in future neonatal-focused trials.

We report on the implementation of electronic hand hygiene monitoring with visual nudges for positive reinforcement of staff hand hygiene adherence in a Swiss third-level neonatal intensive care unit. The weekly average hand hygiene level, though suboptimal, increased from 21% to 41%, being highest with an active nudging function.

BACKGROUND AND AIMS: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study. METHODS: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30–35 weeks and a post-natal age of 0–14 days (“subpopulation of clinical concern”), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough <5 mg/l) dosages in most neonates. RESULTS: In the subpopulation of clinical concern, Ctrough <5 mg/l was predicted in 59% versus 79–99% of cases in all other subpopulations following the current recommendations. Elevated Ctrough values were associated with a post-natal age of less than seven days. Simulations showed that extending the dosing interval to ≥36 h in the subpopulation of clinical concern increased the frequency of a desirable Ctrough below 5 mg/l to >80%. CONCLUSION: Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K. pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K. pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K. pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

In clinical settings with no commonly accepted standard-of-care, multiple treatment regimens are potentially useful, but some treatments may not be appropriate for some patients. A personalized randomized controlled trial (PRACTical) design has been proposed for this setting. For a network of treatments, each patient is randomized only among treatments which are appropriate for them. The aim is to produce treatment rankings that can inform clinical decisions about treatment choices for individual patients. Here we propose methods for determining sample size in a PRACTical design, since standard power-based methods are not applicable. We derive a sample size by evaluating information gained from trials of varying sizes. For a binary outcome, we quantify how many adverse outcomes would be prevented by choosing the top-ranked treatment for each patient based on trial results rather than choosing a random treatment from the appropriate personalized randomization list. In simulations, we evaluate three performance measures: mean reduction in adverse outcomes using sample information, proportion of simulated patients for whom the top-ranked treatment performed as well or almost as well as the best appropriate treatment, and proportion of simulated trials in which the top-ranked treatment performed better than a randomly chosen treatment. We apply the methods to a trial evaluating eight different combination antibiotic regimens for neonatal sepsis (NeoSep1), in which a PRACTical design addresses varying patterns of antibiotic choice based on disease characteristics and resistance. Our proposed approach produces results that are more relevant to complex decision making by clinicians and policy makers.