Journal of Infection

BackgroundRecurrent sore throat affects a small minority of adults but can cause substantial morbidity. Evidence to guide tonsillectomy eligibility in adults is limited, and current criteria are extrapolated from paediatric populations. We aimed to describe the epidemiology, management, and prognosis of adult sore throat in UK primary care. MethodsUsing CPRD Aurum (2010-2020 adults with a first coded episode of sore throat or tonsillitis were identified and matched to controls. Episode frequency, antibiotic use, ENT referral, and tonsillectomy were analysed. Predictors of recurrent episodes ([≥]3 in 365 days), referral, and tonsillectomy were assessed using time-to-event, multinomial logistic, and multilevel mixed-effects regression models. FindingsOf 4.45 million adults, 1.70 million (38.3%) had [≥]1 episode; most (61.5%) had only one, but 4.1% experienced [≥]3 within 1 year. Recurrent episodes were more common in younger females and those from more deprived areas. Only 21,869 patients (0.5% of the exposed cohort) underwent tonsillectomy, and just 25.7% of these met Paradise criteria at any time; conversely, only 13.9% of those meeting criteria underwent surgery. Patients who had a tonsillectomy tended to be younger, female, and from less deprived areas. Pre-tonsillectomy episode rates were unexpectedly low, but the data indicated that individuals with high baseline burden continue to experience elevated episode rates over several years. ConclusionsRecurrent sore throat is uncommon, but those affected face substantial disease burden. Current tonsillectomy patterns are poorly aligned with disease burden and show inequities by deprivation. Earlier identification of adults likely to develop recurrent episodes, and more timely surgical intervention, may improve patient outcomes and the cost-effectiveness of tonsillectomy.

ObjectivesDiagnosis of community-acquired Legionnaires disease (CALD) relies on microbiological testing. Routine testing in hospitalised CAP patients has low positivity rates. We externally validated a Legionella prediction score, assessed its applicability in routine care, and explored potential updates. MethodsWe analysed data from 196 CALD patients from 20 Swiss hospitals and 196 Legionella-negative CAP controls matched by date of diagnosis ({+/-}14 days; August 2022-March 2024). We assessed the availability of the original score predictors (fever, no/dry cough, hyponatremia, elevated CRP, elevated LDH, low platelet count) in routine care and the original scores discriminative performance. The dataset was split into development and validation cohorts to evaluate whether simplifying modifications improved predictive performance. ResultsThe original score showed 91% (95% CI: 86-96%) sensitivity and 35% (95% CI: 28-42%) specificity at a cut-off [&ge;]2; LDH was infrequently measured, and platelet count was a poor predictor. The simplified SwissLEGIO score (fever >38{degrees}C, sodium <133 mmol/L, CRP >180 mg/L, no/dry cough, prior {beta}-lactam therapy) maintained high sensitivity (88-92%) and showed improved specificity (46-58%) at cut-off [&ge;]2. ConclusionThe SwissLEGIO score is an easy-to-apply screening tool to rule out CALD in hospitalised CAP patients with scores <2 and may reduce testing by 36-52% at a CALD prevalence of 4%.

BackgroundElectronic prescribing registries are widely used for antimicrobial stewardship surveillance. Existing indicators predominantly measure structure or process, while validated outcome indicators remain rare. The present study evaluates how well rule-based measures capture clinically meaningful postdiagnostic antibiotic decision making in pediatric febrile urinary tract infection. MethodsWe conducted a retrospective, multicenter validation study including all empirically treated febrile UTI episodes across three Swedish pediatric emergency departments. Prescribing outcomes were classified using registry rules and compared with outcomes determined by clinician review and laboratory findings. Guidance Ratio (GR) and Discontinuation Ratio (DR) were calculated monthly and in aggregate for both clinically validated- and registry rule classifications. ResultsIn total, 909 febrile UTI episodes were included across all sites. The rule-based GR was 49%. GR increased consistently with stronger diagnostic evidence. Among the 431 episodes with clinician-adjudicated follow-up, 63% resulted in guided treatment; 28% discontinued treatment, and 9% lacked follow-up documentation. The rule-based algorithm showed a sensitivity of 0.78 and a specificity of 1.00 for identifying guided outcomes. Monthly rule-based GR tracked validated temporal patterns but underestimated absolute values. A calibration function substantially improved agreement. ConclusionsRule-based indicators captured overall prescribing patterns but underestimated the level of prescribing concordant with guidelines. Validation against clinician reviewed reference data enabled calibration and improved the interpretability of indicators based on registry data for antimicrobial stewardship.

BackgroundSevere Fever with Thrombocytopenia Syndrome (SFTS) is an acute infectious disease with high mortality. This study aimed to develop a quantitative scoring system for grading SFTS severity using dynamic clinical data. MethodsA retrospective study included 547 confirmed SFTS patients from two hospitals. Clinical data were collected over a 14-day course (divided into four phases). Patients were grouped into survivors (n=451) and non-survivors (n=96). Statistical analyses, including Kaplan-Meier curves and log-rank tests, were performed. An external validation cohort of 44 new patients was used to validate the scoring system via C-statistic, calibration curves, and decision curve analysis (DCA). ResultsOf 547 patients, 96 (17.55%) were non-survivors. Multivariate logistic regression identified six independent prognostic factors across phases: age, platelet (PLT), aspartate aminotransferase (AST), and creatinine (Cr) (days 5-7); age, red blood cell distribution width (RDW), Cr, and lactate dehydrogenase (LDH) (days 8-10); Cr and LDH (days 11-14). A scoring system (0-11 points) was developed, stratifying patients into low (0-3), intermediate (4-7), and high (8-11) risk groups, with adverse outcome rates of 1.04%, 22.92%, and 76.04%, respectively. Kaplan-Meier curves showed significant prognostic differences (log-rank P<0.001). External validation (44 cases) confirmed excellent performance: AUC 0.810-0.952, good calibration (Hosmer-Lemeshow P>0.05), and net clinical benefit (DCA Eavg 0.068-0.098, Emax 0.422-0.559). ConclusionA dynamic SFTS severity scoring system was developed and validated. Internal and external validation confirmed its reliability and clinical utility, providing a simple, practical tool for timely assessment and early intervention.

Background Five-biomarker-defined hypervirulent Klebsiella pneumoniae (hvKp) causes invasive infections, but its burden in bloodstream infections versus classical K. pneumoniae (cKp) is unclear. Methods This retrospective cohort study at a tertiary hospital in Japan included K. pneumoniae bloodstream infection episodes from January 2022-December 2024. hvKp was defined by the presence of all 5 genotypic biomarkers (rmpA, rmpA2, iucA, iroB, and peg-344). The primary outcome was abscess complications, and secondary outcomes were length of stay and antibiotic duration. Whole-genome sequencing was performed for 164 isolates. Results Among the 207 episodes, 28 (14%) were of hvKp. Abscess complication occurred in 17 (61%) hvKp versus 23 (13%) cKp episodes (adjusted odds ratio 10.7; 95% CI, 4.36-26.2). Median length of stay in hvKp versus cKp was 28 versus 14 days (adjusted ratio 1.60; 95% CI, 1.18-2.16) and median antibiotic duration was 43 versus 14 days (adjusted ratio 2.13; 95% CI, 1.64-2.77). These associations were attenuated after adjusting for abscess-related complications. No significant difference in 30-day mortality was observed, although the study was underpowered. Multidrug resistance was less frequent in hvKp strains than in cKp strains (11% vs. 30%; P = .040). Among the sequenced hvKp episodes, abscess rates varied across lineages, from 9 of 10 in ST23 to 1 of 4 in ST412. Conclusions Five biomarker-defined hvKp strains delineated a bloodstream infection subgroup with frequent abscess complications and prolonged care. hvKp and cKp present distinct clinical challenges; diagnostic tools distinguishing these subgroups may aid abscess evaluation and source control.

BackgroundAn upsurge in Streptococcus pyogenes infections 2022-2023 highlighted potential benefits of point-of-care tests (POCT) to support clinical pathways, prevent outbreaks, and optimise antibiotic use. ObjectivesWe conducted a pilot research study in a west London paediatric emergency department (ED) to determine whether a molecular POCT had potential to alter management in children who were also having a conventional throat swab taken for culture. MethodsChildren <16 years presenting to ED who had a throat swab requested by a clinician were invited to have a second swab taken for research purposes only. Clinical management was unaffected by the research swab result, which was processed using a molecular POCT that was not approved for use in the host NHS Trust. ResultsPrevalence of streptococcal infection was low during the study (May 2023-June 2025); swab positivity in symptomatic children was 12.8% (6/47). Overall, 38/49 (77.6%) participants who had throat swabs received antibiotics. Of those children recommended to receive antibiotics, 29/38 (76.3%) had a negative POCT. Mean time to reporting of positive throat swab culture results was 3.67 days (range 3-5 days) leading to occasional delay in treatment, although POCT identified positive results within minutes. ConclusionAntibiotic use was frequent and could be avoided or stopped by use of a rule out POCT in over three-quarters of children in the ED, if suspicion of S. pyogenes is the main driver for prescribing. POCT were easy to process and produced immediate results compared with culture, in theory enabling timely decision-making and avoiding treatment delay.

FluSurvey is a participatory surveillance system used to monitor trends in influenza and other respiratory viruses through weekly symptom surveys among the UK population. We aimed to characterise the wider impact of "influenza-like illnesses" (ILI) among FluSurvey participants and assess correlations of ILI with other established influenza surveillance systems. We included data reported by FluSurvey participants over the 2023-24 and 2024-25 winter seasons. Using weekly symptoms surveys, we derived ILI episodes and estimated the proportion reporting healthcare service use, medication use, impact on daily life, absenteeism and use of tests. We applied existing methodologies (omitting first report and weighting to the age-sex structure of England) and assessed cross-correlations of weekly FluSurvey ILI rates with the national surveillance of GP ILI consultations, influenza hospital admissions, and influenza PCR test positivity at time lags of up to +/- 2 weeks. There were 3057 participants over two winter seasons (N2023-24=2540, 63% female, mean age 60 years; N2024-25=2273, 64% female, mean age 61 years). Of 1868 ILI episodes, only a minority contacted healthcare services (14%, most frequently visiting the GP). A large proportion of episodes reported medication use (89%), impact on daily life (75%) and missing school or work (47%). Notable differences in testing behaviour were apparent by season, with fewer reporting use of tests in 2024-25. FluSurvey ILI rates were strongly correlated with other influenza surveillance, predominantly leading GP ILI consultations (max r=0.73), coinciding with influenza hospital admissions (max r=0.88) and lagging influenza test positivity (max r=0.88). The majority of ILI reported to FluSurvey do not contact healthcare due to symptoms but experienced wider impacts on daily life. FluSurvey ILI corresponds well with other national influenza surveillance and provides broader context on community illness, supplementing the monitoring of influenza activity for public health response.

BackgroundAntibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. MethodsWe conducted a retrospective analysis of antibiotic importation records from the Tanzania Medicines and Medical Devices Authority for 2010-2016. Systemic antibiotics for human use imported via oral or parenteral routes were included. Unit prices (USD per smallest unit of measure) were summarized using the median and interquartile range (IQR). Prices were compared by route of administration, supplier country, and product naming practice (INN-named versus brand-named) using Mann-Whitney U and Kruskal-Wallis tests with false discovery rate adjustment. ResultsOf the 14,301 records, 10,894 (76.2%) met the inclusion criteria. Oral antibiotics predominated (89.6%). Although the median oral antibiotic prices declined over time, substantial price dispersion persisted across all study years. Parenteral antibiotics were consistently more expensive (USD 0.755-3.370) and more variable than oral antibiotics. Importation was concentrated in a few medicines, with amoxicillin-clavulanate (16.7%) and amoxicillin (11.4%) accounting for over one-quarter of records, and in a few supplier countries, with India representing 44.9% of the records. Significant price differences between INN-named and branded products were observed for amoxicillin (adjusted p<0.001) and ciprofloxacin (adjusted p=0.018), whereas prices differed significantly by supplier country across major medicines (adjusted p<0.05). Across medicines and years, wide within-product price distributions indicate persistent market segmentation rather than price convergence. ConclusionsAntibiotic import prices in Tanzania exhibit systematic and reproducible variations associated with formulation type, supplier origin, and product naming practices. The findings indicate that procurement structure and supplier participation strongly influence pricing in the import-dependent pharmaceutical market. Monitoring import-level prices can serve as an upstream indicator of market conditions and support evidence-informed procurement, pricing regulations, and antimicrobial stewardship policies in LMIC settings.

Infections caused by carbapenem-producing Enterobacterales (CPEs) are a persistent and growing threat in healthcare settings. Yet, current infection prevention and control (IPC) surveillance methods, which largely rely on the spatial and temporal proximity of patients, often misattribute or miss infection transmission events. Here, we develop and retrospectively evaluate an integrated methodology that combines analyses of ward-level patient movement data and whole-genome sequencing (WGS) data analyses, providing measures of bacterial and plasmid similarity. Specifically, we evaluate this methodology across two datasets: a CPE outbreak of diverse carbapenem types (103 genomes, January 2021 to March 2021) and an Imipenem-Hydrolysing beta-lactamase-positive CPE outbreak (82 genomes, June 2016 to October 2019), using standard clinical criteria and conservative genomic thresholds to quantify how often current IPC surveillance methods correctly identify genomically confirmed transmission events. Findings show that, across 3,423 patient contact-genome pairs, current IPC surveillance methods detected only 20.5% of genomically confirmed transmission events whilst maintaining 98.5% specificity, with missed events arising from temporal, spatial, and cross-species, mechanistic blindspots. In contrast, WGS-enabled IPC surveillance methods provided a 25 to 47-day earlier detection window and, in a linked economic evaluation, delivered annualised savings of up to GBP 3.6 million, as well as a return on investment exceeding 2-fold in 7 of 8 cost scenarios. By operationalising high-throughput WGS data analysis with clinically relevant patient movement data, we evidence that it may be possible to disrupt and thereby mitigate the effects of AMR-driven CPE outbreaks, supporting investigations into the adoption of WGS-enabled IPC surveillance as a standard-of-care tool.

Lancefield group C/G streptococci (GCS/GGS) are increasingly recognised as significant human pathogens that cause a disease spectrum similar to Streptococcus pyogenes. Despite their high clinical burden in the UK, their genomic diversity remains poorly understood. We performed whole-genome sequencing (WGS) on a prospective collection of 109 consecutive GCS/GGS isolates from all infection types in Sheffield, UK, over five months in 2020. Streptococcus dysgalactiae subsp. equisimilis (SDSE) accounted for 104 isolates, while five were identified as Streptococcus canis. The SDSE population was highly diverse, comprising 15 genomic clusters and 38 unique emm-ST combinations. We identified the presence of the ST20/stG62647 international lineage (24% of isolates), a cluster globally associated with severe invasive disease. Antimicrobial resistance genes were prevalent (49%), predominantly linked to mobile genetic elements carrying tetracycline and macrolide resistance. Furthermore, a variation in the penicillin-binding protein PBP2X (P601L) was linked to reduced penicillin sensitivity (MIC 0.03 mg/L). There were few or no genetic changes in isolates obtained from the same patient, even when they were collected 8-10 weeks apart, indicating long-term persistence within a host. The unexpected detection of S. canis in human infections and the high diversity of SDSE, persistence and virulence-associated regions underscore the need for enhanced national genomic surveillance to track emerging virulent and antibiotic-resistant SDSE lineages. Impact statementLancefield group C and G streptococci, most often the species Streptococcus dysgalactiae subsp. equisimilis (SDSE), are an increasingly significant human pathogen, often mirroring the severity of infections caused by Lancefield group A Streptococcus (S. pyogenes). Despite its clinical importance, we know little about the population of SDSE circulating in the UK. This study provides the first comprehensive genomic analysis of SDSE isolates from a single UK region, identifying a highly diverse population comprising 15 distinct genomic clusters but with evidence of long-term persistence within a single host. Notably, we confirm the presence of the international stG62647/ST20 lineage in the UK, which is globally associated with severe invasive disease. Our findings also reveal a high prevalence of antimicrobial resistance genes ([~]49%), primarily linked to mobile genetic elements, and the presence of a specific variation in the penicillin-binding protein PBP2X that reduces penicillin sensitivity. Additionally, the unexpected detection of S. canis in human infections rather than animals highlights a need for monitoring. By defining the UKs SDSE population structure and its resistance landscape, this research underscores the critical need for enhanced national genomic surveillance to track emerging high-virulence and antibiotic-resistant lineages Data summarySequence files for isolates from Sheffield used for this study have been uploaded to the sequence read archive with project accession number PRJNA1333937 and accession numbers provided in Supplementary Dataset 1. The completed genome for SDE096 been deposited on GenBank with the accession number JBSXMJ000000000.

ObjectiveUrine cultures are frequently requested at an early stage in primary care and outpatient settings, often without a comprehensive clinical assessment. This practice increases healthcare costs and laboratory workload and may lead to misleading results due to asymptomatic bacteriuria and specimen contamination. This study aimed to evaluate whether routinely reported microscopic urinary leukocyte findings can predict urine culture positivity under real-world clinical conditions. The distribution of isolated microorganisms and the frequency of mixed or contaminated growth were assessed. MethodsThis retrospective, laboratory-based diagnostic accuracy study included all urine samples sent for culture over a one-year period at a tertiary care hospital, provided concurrent microscopic urinalysis was available. No additional clinical exclusion criteria were applied to reflect the routine practice. Leukocyte findings were reported semi-quantitatively and analyzed both categorically and as approximate numerical values. The urine culture results were classified as positive, negative, or mixed/contaminated growth. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. ResultsA total of 8,478 urine samples were analyzed in this study. Urine culture positivity was detected in 2,666 (31.4%) samples, whereas 5, 812 (68.6%) showed no growth. Culture positivity increased significantly with higher leukocyte levels (p < 0.001), ranging from 13.1% in the lowest category to 83.1% in samples with abundant leukocytes. ROC analysis demonstrated an acceptable discriminative performance (AUC = 0.747). The Youden index identified an optimal threshold of approximately 5.5 leukocytes per high-power field, with a sensitivity of 60.4% and a specificity of 77.8%. Mixed or contaminated growth was the most common finding among culture-positive samples (43.5%), followed by Escherichia coli (29.5%). ConclusionMicroscopic urinary leukocyte findings were significantly associated with urine culture positivity and demonstrated acceptable predictive performance in real-world clinical practice settings. Although leukocyte microscopy alone is not diagnostic, it may support more selective urine culture ordering, reduce contamination, and contribute to rational diagnosis and antimicrobial management in primary care.

ObjectivesTo identify and validate plasma host-response protein biomarkers that improve discrimination of bacterial infection in febrile infants [&le;]90 days of age, and to assess whether novel biomarkers add value beyond established markers. MethodsSub-study of the prospective multicentre Febrile Infant Diagnostic Assessment and Outcome (FIDO) cohort. Novel biomarkers were identified through plasma proteomic profiling (Olink(R)) and combined with biomarkers and signatures from the literature for verification using Luminex and ELISA platforms. Diagnostic performance of novel biomarkers, established markers (CRP, PCT), and multi-protein signatures was evaluated. ResultsProteomic profiling of 110 samples identified 174 proteins differentially expressed between bacterial and viral infections, revealing distinct pathogen-specific immune signatures. Verification in the full cohort (n=445) demonstrated PCT had the highest individual accuracy for invasive bacterial infection (IBI) (AUC 0.89). Combining PCT with novel biomarkers, particularly lipocalin-2 (LCN2), improved discrimination (AUC 0.96). Diagnostic performance for the combined IBI/urinary tract infection (UTI) outcome was consistently lower (AUC <0.8). ConclusionsFebrile infants demonstrate biologically coherent host-response signatures that can be leveraged diagnostically. A PCT-LCN2 combination showed excellent accuracy for identifying IBI and may support future biomarker-guided diagnostic strategies, while reliable discrimination of UTI remains challenging.

ObjectiveTo evaluate the diagnostic performance of FeverPAIN and Centor with point-of-care test (POCT) results for Group A Streptococcus (GAS) among children and adults presenting with sore throat in community pharmacies. MethodsCross-sectional analysis of patients aged six years and over with sore throat presenting to community pharmacies across Wales delivering the Sore Throat Test and Treat (STTT) service from November 2018 to September 2024. Patients who scored FeverPAIN [&ge;]2 or Centor [&ge;]3 and were able to undergo POCT were eligible for analysis. We described GAS positivity by age group and assessed diagnostic performance of FeverPAIN at the National Institute for Health and Care Excellence (NICE) antibiotic threshold ([&ge;]4), reporting sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). We estimated potential overtreatment and undertreatment if antibiotics were supplied based on FeverPAIN alone. ResultsAmong 73,617 eligible patients, 37.0% (n=27,220) tested POCT-positive for GAS. Positivity was highest in children aged 6-10 years (47.0%: 5,339/11,371). FeverPAIN was used in 92.5% (n=68,099) of assessments. At the NICE-recommended threshold for antibiotic treatment (FeverPAIN [&ge;]4), sensitivity was 55.0% (95% CI: 54.4-55.6%) and specificity 77.0% (95% CI: 76.6-77.4%). PPV was 57.6% (95% CI: 57.0-58.2%) and NPV 75.1% (95% CI: 74.7-75.5%). Overall AUROC was 0.70 (95% CI: 0.70-0.71), with the lowest AUROC of 0.69 (95% CI: 0.68-0.70) observed among children aged 6-10 years. Using FeverPAIN alone would undertreat 44% and overtreat 23% of patients based on POCT results. ConclusionsFeverPAIN alone showed limited diagnostic performance for identifying GAS, with more pronounced discordance observed among children. Incorporating POCTs within community pharmacy sore throat pathways may support more targeted antibiotic prescribing. Our findings support a re-evaluation of the role of POCTs within community pharmacy sore throat pathways.

Objective. To evaluate the diagnostic and prognostic significance of C reactive protein (CRP) level dynamics within the first five days after surgery for the early detection of surgical site infections (SSI) and to identify independent risk factors, taking into account regional specifics of surgical management (types of surgeries, duration of procedures), as well as the local hospital microbial landscape. Materials and Methods. A single-center retrospective cohort analysis of data from 127 patients who underwent surgical procedures between 2022 and 2024 was conducted. CRP levels on postoperative days 1, 3, and 5 were assessed, and delta values were calculated. Descriptive statistics, ROC analysis, and multivariate logistic regression were used to identify predictors of SSI. Results. Patients with SSI lacked the physiological decrease in CRP levels by day 5. The most informative indicator was the CRP level on day 3: a threshold of >106 mg/L was associated with a high risk of SSI (AUC=0.76; sensitivity 85%, specificity 63%). Independent predictors of SSI included surgery duration (OR=1.015 per 1 min; p<0.001) and the increase in CRP between days 3 and 5 (delta CRP3-5: OR=1.027; p=0.023). A combined model (clinical parameters + CRP) demonstrated the highest predictive ability (AUC=0.79). Conclusion. Monitoring CRP dynamics, particularly on days 3 and 5, is a highly informative and accessible method for the early diagnosis of SSI. A CRP threshold of >100 mg/L on day 3 and its subsequent increase should serve as a trigger for in-depth diagnostic investigation and rationalization of antimicrobial therapy. Keywords: C reactive protein, postoperative complications, surgical site infection, antibiotic therapy, predictive factors, diagnosis

Streptococcus pneumoniae is the leading cause of empyema and pneumonia in children, and monitoring of effectiveness of polyvalent pneumococcal vaccines has been essential for controlling invasive pneumococcal disease (IPD) in children and elderly adults. Conventional serotyping of pneumococci has relied on Quellung reaction following laboratory culture, however more recently whole genome sequencing (WGS) has been implemented in many reference laboratories to enhance traditional typing. Pleural fluid samples from cases with empyema are often culture negative, limiting the utility of WGS and requiring polymerase chain reaction (PCR) or 16S rRNA sequencing to detect S. pneumoniae. These molecular methods have limited sensitivity and capacity to characterise pneumococcus in clinical samples, especially in specimens with a low pathogen abundance. This study applied capture-based enrichment (tNGS) to identify and characterise S. pneumoniae directly from pleural fluid samples. A total of 51 pleural fluid samples were subjected to tNGS with a custom probe panel, for 39 known positive fluids collected from IPD cases between 2018-2025 in New South Wales, Australia. tNGS results were benchmarked against molecular-based serotyping. Our tNGS achieved 100% sensitivity and specificity in detecting S. pneumoniae. Serotyping results were concordant with PCR and 95% (37/39) of S. pneumoniae PCR positive pleural fluid cases could be serotyped using tNGS. Standard molecular methods however could only determine serotype in 56% (22/39) of samples. This tNGS enabled 39% improvement in ability to directly identify and serotype IPD-associated serotypes of S. pneumoniae in difficult-to-culture pleural fluids can significantly enhance laboratory surveillance of IPD as well as our understanding of vaccine effectiveness.

Objectives: Optimising parenteral antimicrobial use is central to antimicrobial resistance (AMR) control, yet its appropriateness is difficult to assess. We aimed to develop a quantitative indicator to evaluate the appropriateness of parenteral antimicrobial therapy in hospitalised patients with bloodstream infections. Methods: We developed the Susceptibility-Spectrum Discrepancy Index (S2DI), reflecting the discrepancy between antimicrobial susceptibility of blood culture isolates and the spectrum width of prescribed agents. Using a database from 67 National Hospital Organization hospitals in Japan, we identified patients with Staphylococcus aureus or Escherichia coli bacteraemia from 2017 to 2023. An expert panel of 10 infectious disease physicians independently ranked antimicrobial susceptibility (A) and spectrum width of commonly used agents (B). S2DI was defined as B minus A on day 7 after treatment initiation, with values closer to zero indicating more appropriate therapy. S2DI was calculated for individual cases, aggregated at the hospital level, and analysed using linear mixed-effects models with hospital-level random effects. Results: A total of 4,505 S. aureus and 9,563 E. coli bacteraemia cases were included. Median S2DI was 1 (IQR 0-1) for S. aureus and 2 (IQR 0-3) for E. coli. For both pathogens, later calendar years were significantly associated with more favourable S2DI, suggesting gradual improvement in antimicrobial use. In E. coli bacteraemia, female sex and younger age were also associated with more appropriate therapy. Conclusions: Although variation across hospitals persists, appropriateness of parenteral antimicrobial use has improved over time. S2DI is a simple metric that may support optimisation of antimicrobial use.

Introduction Data on bloodstream infections (BSI) indicate a growth in incidence over time. This analysis utilised national data from England and the best available United States (US) evidence to predict BSI incidence over the years 2025 to 2029. The analysis utilised evidence on the cost-effectiveness of molecular rapid diagnostic tests (mRDT) to estimate the cost and mortality associated with BSI, and the potential for increased use of mRDT to save lives. Methods Data on BSI incidence by age group and sex for England in 2017 and the US (Minnesota) for 2003 to 2005 were combined with demographic projections over the years 2025 to 2029 to estimate the number of BSIs. Published costs and mortality associated with BSI, according to the method of identification of the pathogen, were used to estimate the lives saved and the cost impact of widespread use of mRDT in England and the US. Results BSI cases in England and the US are predicted to total 1.02 million and 6.24 million over the years 2025 to 2029, associated costs are GBP14.6 million and $221 million, respectively. Expanding the use of mRDT would save 2,219 and 7,554 lives in England and the US, respectively, over a 5-year period and would reduce healthcare expenditure in both countries. Conclusion There is a compelling argument to increase the uptake of mRDT to improve patient outcomes. This analysis demonstrates that expanded mRDT adoption can significantly reduce BSI burden, saving over 9,700 lives and decreasing healthcare expenditure in both countries.

BackgroundThe epidemiology of suspected pediatric meningoencephalitis has shifted in the era of conjugate vaccines and multiplex PCR diagnostics, with viral pathogens now predominating over bacterial causes. Updated epidemiologic data are essential to adapt diagnostic and therapeutic algorithms to current clinical practice. MethodsThis retrospective single-center study included children and adolescents <18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary-care pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire(R) FilmArray(R) Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric group comparisons, receiver operating characteristic analyses. ResultsAmong 1,198 included children, definite bacterial meningitis was diagnosed in 13 (1.1%), definite viral meningitis in 80 (6.7%), aseptic meningitis of unknown etiology in 131 (11.0%), confirmed/probable encephalitis in 53 (4.4%), and possible encephalitis in 34 (2.8%). Bacterial meningitis accounted for 5.8% of all meningitis cases. A causative pathogen was identified in all bacterial meningitis cases, most commonly Streptococcus pneumoniae (n = 7). Enterovirus (n = 52) and parechovirus (n = 9) predominated in viral meningitis, whereas an infectious etiology was identified in only 13 of 53 confirmed/probable encephalitis cases. The Bacterial Meningitis Score showed a sensitivity of 80.0% and a specificity of 57.6%. The recently published UK-ChiMES-pre- and post-lumbar puncture scores demonstrated sensitivities of 84.6% and 76.9% and specificities of 86.3% and 92.7%, respectively. DiscussionBacterial meningitis was rare in this contemporary cohort, while viral and etiologically unresolved infections predominated despite routine multiplex PCR diagnostics. Clinical prediction scores supported risk stratification, with the UK-ChiMES-pre-lumbar puncture score showing the most favorable balance between sensitivity and specificity and potential to guide diagnostic decisions and antiinfective therapy.

Background: CD276 has been proposed as a candidate gene associated with the biological characteristics of meningioma, but its predictive position and interpretive significance within a transcriptomic classifier have not yet been clearly established. Accordingly, this study aimed to evaluate CD276 stepwise across internal model development, external validation, calibration, decision-analytic assessment, feature stability, and robustness analyses using public transcriptomic cohorts. Methods: The analyses in this study were organized into two interconnected notebooks. In Notebook A, we reconstructed the internal training cohort (GSE183653), evaluated the CD276 single-gene signal, and then developed a transcriptome-wide multigene classifier. We also performed permutation importance, bootstrap confidence interval, label permutation test, repeated cross-validation, CD276 ablation, and internal calibration analyses. In Notebook B, we reproduced the external validation cohort (GSE136661) in a fixed common-gene space, applied train-only recalibration and train-only threshold transfer, and extended the interpretation through decision curve analysis, stability analysis, enrichment analysis, and one-factor-at-a-time robustness analysis. Results: The internal training cohort consisted of 185 samples and 58,830 genes, of which 25 were WHO grade III cases. CD276 expression showed a significant association with WHO grade, but the internal discrimination of the CD276-only baseline was limited (ROC-AUC 0.628, average precision 0.323, balanced accuracy 0.540). In contrast, the initial transcriptome-wide model showed ROC-AUC 0.834 and PR-AUC 0.509, and under 5-fold cross-validation, the canonical fulltranscriptome model and the CD276-forced 5,001-feature branch showed mean ROC-AUC/PR-AUC of 0.854/0.564 and 0.855/0.606, respectively, outperforming the CD276-only baseline at 0.644/0.391. CD276 was not included in the initial 5,000-feature filtered set and ranked 900th among 5,001 features even in the forcibly included 5,001-feature branch. In paired ablation analysis, the performance difference attributable to inclusion of CD276 was effectively close to zero (delta ROCAUC 0.000062, delta PR-AUC 0.000056). Internal calibration analysis showed an overconfident probability pattern (Brier score 0.10501, intercept -1.421392, slope 0.413241). In external validation, the fixed multigene pipeline achieved ROC-AUC 0.928 and PR-AUC 0.335. Train-only recalibration improved calibration metrics while preserving discrimination, and decision curve analysis showed threshold-dependent but limited external utility. Stability analysis showed overlap between core-stable genes and high-impact genes, but CD276 was not supported as a dominant stable core feature and remained in the target-of-interest tier. In robustness analysis, some perturbations preserved the primary interpretation, whereas others revealed transform sensitivity or an alternative high-performing feature-space solution. Conclusions: CD276 is a gene of interest associated with meningioma grade, but it was difficult to interpret it as a strong standalone predictor or a dominant stable classifier feature. In this study, the main basis of predictive performance lay not in CD276 alone but in a broader multigene transcriptomic structure, and probability output needed to be interpreted conservatively with calibration taken into account. These findings position CD276 not as a direct single-gene classifier but as a biologymotivated target-of-interest that should be interpreted within a broader transcriptomic program.

ObjectiveTo quantify the seasonal burden of acute respiratory viral infections among healthcare workers (HCWs), characterize virologic etiologies, and identify predictors of symptomatic illness and sick leave. MethodsWe conducted a prospective cohort study of HCWs during winter 2024-2025, with weekly surveys capturing acute respiratory infections (ARI) and sick leave. Nasal-throat multiplex PCR swabs were self-collected during symptomatic episodes. Incidence rate ratios (IRRs) for symptomatic episodes and sick days were estimated using Poisson regression; presenteeism was assessed among febrile episodes. ResultsAmong 655 HCWs, 400 (61.1%) reported [&ge;]1 symptomatic episode. Over 70,861 person-days, incidence rates were 1.34 symptomatic episodes and 0.82 sick days per 100 person-days. Among PCR-confirmed episodes (n=112), rhinovirus (45.5%) and influenza (23.2%) predominated. Female sex was associated with higher rates of symptomatic episodes (IRR 1.38, 95% CI 1.11-1.72) and sick days (IRR 2.55, 95% CI 1.62-4.00), while age >56 years was associated with lower rates of both. During febrile episodes, 38.8% (95% CI 31.5%-46.6%) reported working despite fever. ConclusionsARIs were common among HCWs and frequently resulted in sick leave, yet febrile presenteeism remained substantial, underscoring the need for strengthened respiratory virus prevention and occupational health policies.