Infection

IntroductionRespiratory Syncytial Virus (RSV) is a major cause of morbidity in older adults. With the emergence of the coronavirus disease 2019 (COVID-19) and the subsequent changes in respiratory viral circulation, it is crucial to reassess RSV-associated healthcare burden in adults. This study assessed RSV-associated healthcare burden in adults in six European countries before and during the COVID-19 pandemic. MethodsWe conducted a retrospective analysis using national hospital admissions data from Denmark, England, Finland, the Netherlands, Scotland, and regional surveillance data from the Valencia region (Spain). We included patients aged [≥]18 years hospitalised for respiratory tract infections (RTIs) from 2016 to 2023. We assessed RSV-coded and laboratory-confirmed hospitalisations, intensive care unit (ICU) admissions, in-hospital length of stay (LOS), and mortality. ResultsRSV-associated hospitalisations significantly reduced during the 2020/2021 season across all countries, coinciding with strict COVID-19 preventive measures, but resurged in subsequent seasons. We observed the highest hospitalisation rates in adults aged [≥]85 years. RSV-coded hospitalisations were found to underestimate the true burden when compared with laboratory-confirmed cases. Underestimation factors ranged from 1.1 to 4.3 times across countries. No significant differences were observed in LOS or ICU admission rates for RSV-associated hospitalisations compared to RTIs. DiscussionOur findings underscore the complex epidemiology of RSV in older adults. The differences between RSV-coded and laboratory-confirmed cases highlight the critical need for improved surveillance and diagnostic practices to better assess the true burden. Our findings could be vital for guiding public health strategies, particularly with the recent introduction of RSV vaccines for older adults.

BackgroundRespiratory syncytial virus (RSV) infections cause an estimated 22-50 million episodes of acute lower respiratory infections (ALRI) every year in children younger than 5 years. To date, no overall estimate of RSV-associated hospitalisations in children under 5 years has been published for the European Union (EU). Through statistical modelling, we estimated the RSV hospitalisation burden in children under 5 years of age in EU countries and Norway, by age group and country. MethodsWe collated national RSV-associated hospitalisation estimates calculated using linear regression models in children under 5 years via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands and Scotland during 2006-2018. A systematic literature review was conducted to collect additional estimates. Using the multiple imputation and nearest neighbour matching extrapolation methods, we estimated RSV-associated hospitalisation rates in all EU countries. ResultsAdditional estimates for Spain and France were found in the literature and added to the analysis. We estimated that an average of 245,244 (95%CI 224,688-265,799) hospital admissions with a respiratory infection per year were associated with RSV in children under the age of 5, with most cases occurring among children aged less than 1 year (75%). Infants aged less than 2 months represented the most affected group (71.6 per 1,000 children; 95%CI: 66.6-76.6). The hospitalisation rates varied widely across countries: for example, estimated rates in the 0-2 months age group ranged from 47.4 (37.5-57.3) per 1,000 in the Netherlands to 98.3 (88.5-108.1) per 1,000 in France. ConclusionTo our knowledge, this is the first attempt to estimate the overall RSV hospitalisation burden in children under the age of 5 years in the EU. Our findings will help support decisions regarding prevention efforts, and they will also represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunisation programs in Europe.

BackgroundRespiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in older adults that can result in hospitalisations and death. Estimating RSV- associated hospitalisation is critical for planning RSV-related healthcare needs for the ageing population across Europe. MethodsWe gathered national RSV-associated hospitalisation estimates from the REspiratory Syncytial virus Consortium in EUrope (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006 to 2017. We extrapolated these estimates to 28 EU countries using nearest-neighbour matching, multiple imputations, and two sets of 10 indicators. ResultsOn average, 158 229 (95%CI: 140 865-175 592) RSV-associated hospitalisations occur annually among adults in the EU (above 18 years); 92% of these hospitalisations occur in adults over 65 years. Among 75-84 years old, the annual average is estimated at 74 519 (95%CI: 69 923-79 115) at a rate of 2.24 (95%CI: 2.10-2.38) per 1000 adults. Among adults aged [≥]85 years, the annual average is estimated at 37 904 (95%CI: 32 444-43 363) at a rate of 2.99 (95%CI: 2.56-3.42). ConclusionOur estimates of RSV-associated hospitalisations in older adults are the first analysis integrating available data to provide estimates of the disease burden in this population across the EU. Importantly, for a condition which was considered in the past to be primarily a disease of young children, the average annual hospitalisation estimate in adults was lower but of a similar magnitude to the estimate in young children aged 0-4 years: 158 229 (95%CI: 140 865-175 592) versus 245 244 (95%CI: 224 688 -265 799).

Background The COVID-19 pandemic has caused significant global mortality. Despite declining infection rates, new variants of SARS-CoV-2 continue to emerge, necessitating new prevention strategies. Objective This study aimed to evaluate the effect of four over-the-counter (OTC) antiseptic mouthwash/gargling solutions in the U.S., compared with a distilled water control, on SARS-CoV-2 viral load across multiple oral and oropharyngeal sample types. Methods This pilot single-center randomized controlled clinical trial enrolled adults in the San Francisco Bay Area, California, who tested positive for COVID-19. Participants were randomized to distilled water, chlorine dioxide, hydrogen peroxide, cetylpyridinium chloride, and essential oils. Participants were instructed to rinse and gargle four times daily for four weeks using standardized instructions to ensure protocol adherence. Samples were collected on Days 1, 7, and 28 and analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The primary outcome was the change in SARS-CoV-2 viral load from baseline to Day 28, assessed using cycle threshold (Ct) values. Secondary outcomes included self-reported clinical symptoms and hospitalization. Results Forty-nine participants completed the study. No mouthwash demonstrated a statistically significant reduction in SARS-CoV-2 viral load over time. Cetylpyridinium chloride showed a transient increase in Ct values on Day 7 that was not sustained on Day 28. At baseline, throat swab samples had the lowest Ct values across all sample types. Due to limited subgroup sample sizes for secondary outcome measures, no statistical or moderator analyses were conducted. Conclusion Further large-scale randomized trials are needed before recommending antiseptic mouthwashes for SARS-CoV-2 prevention or management.

This study describes two population under age two 1) who received an RSV immunization and 2) experienced RSV-associated hospitalizations since 2018. Results show low uptake of the RSV immunization. RSV-associated hospitalizations exhibited earlier and higher peaks in the 2021/22 and 2022/23 seasons compared to previous years.

BackgroundTo describe whether SARS-CoV-2 viral loads (VLs) and cycle thresholds (CTs) vary by sample type, disease severity and symptoms duration. MethodsSystematic searches were conducted in MEDLINE, EMBASE, BioRxiv and MedRxiv. Studies reporting individual SARS-CoV-2 VLs and/or CT values from biological samples. Paired reviewers independently screened potentially eligible articles. CT values and VLs distributions were described by sample type, disease severity and time from symptom onset. Differences between groups were examined using Kruskal-Wallis and Dunn s tests (post-hoc test). The risk of bias was assessed using the Joanna Briggs Critical Appraisal Tools. Results14 studies reported CT values, 8 VLs and 2 CTs and VLs, resulting in 432 VL and 873 CT data points. VLs were higher in saliva and sputum (medians 4.7x108 and 6.5x104 genomes per ml, respectively) than in nasopharyngeal and oropharyngeal swabs (medians 1.7x102 and 4.8x103). Combined naso/oropharyngeal swabs had lower CT values (i.e. higher VLs) than single site samples (p=<0.0001). CT values were also lower in asymptomatic individuals and patients with severe COVID-19 (median CT 30 for both) than among patients with moderate and mild symptoms (31.4 and 31.3, respectively). Stool samples were reported positive for a longer period than other specimens. ConclusionVLs are higher in saliva and sputum and in individuals who are asymptomatic of with severe COVID-19. Diagnostic testing strategies should consider that VLs vary by sample type, disease severity and time since symptoms onset. SummaryThis systematic review found a higher viral load in saliva and sputum than in nasopharyngeal swabs, in asymptomatic individuals and patients with severe COVID-19. Diagnostic testing strategies should consider the type of sample, disease severity and the time since symptoms onset.

BackgroundRespiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into clinical practice. MethodsFeasibility, performance and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service for patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory intensive care units (ICU) at Guys & St Thomas NHS foundation Trust, London. ResultsRMg was performed on 128 samples from 87 patients during the first 15-weeks providing same-day results for 110 samples (86%) with median turnaround time of 6.7hrs (IQR 6.1-7.5 hrs). RMg was 92% sensitive and 82% specific for clinically-relevant pathogens compared with routine testing. 48% of RMg results informed antimicrobial prescribing changes (22% escalation; 26% de-escalation) with escalation based on speciation in 20/24 cases and detection of acquired-resistance genes in 4/24 cases. Fastidious or unexpected organisms were reported in 21 samples including anaerobes (n=12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus and Legionella pneumophila ST1326, which was subsequently isolated from the bed-side water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A) and Aspergillus fumigatus with multiple treatments and public-health impacts. ConclusionsRMg provides frequent diverse benefits for treatment, infection control and public health. The combination of rapid comprehensive results, alongside revealing and characterising a hidden burden of infections makes the case for expediting routine service implementation.

Ongoing surveillance is essential to inform policy decisions and monitor serotype replacement following pneumococcal conjugate vaccination (PCV) deployment. We report serotype and disease severity trends in this retrospective cohort of hospitalised adults in Bristol-Bath, 2006-22. Of 1686 invasive pneumococcal disease (IPD) cases, 1501 (89.0%) had known serotype. We also identified 2033/3719 cases of non-IPD. IPD declined sharply during the early COVID-19 pandemic. Over 2022 it gradually returned to pre-pandemic levels. Disease severity also changed throughout this period: CURB65 severity and inpatient mortality decreased whilst ICU admissions increased. PCV7 and PCV13-serotype IPD decreased from 2006-09 to 2021-22. However, significant residual PCV13-serotype IPD remains, representing 21.7% [15.5-29.6] of 2021-22 cases, highlighting that significant adult PCV-serotype disease still occurs despite 17-years of paediatric PCV usage in the UK. We found increased proportions of serotype 3 and 8 IPD, whilst 19F and 19A re-emerged. In 2020-22, 68.2% IPD cases were potentially covered by PCV20. Article SummaryWe observed significant serotype shifts but perseverance and re-emergence of some serotypes covered by PCVs over this 17-year retrospective study, which found considerable adult pneumococcal disease attributable to PCV-serotypes despite high uptake of paediatric PCV.

As COVID-19 testing is rolled out increasingly widely, the use of a range of alternative testing methods will be beneficial in ensuring testing systems are resilient and adaptable to different clinical and public health scenarios. Here, we compare and discuss the diagnostic performance of a range of different molecular assays designed to detect the presence of SARS-CoV-2 infection in people with suspected COVID-19. Using findings from a systematic review of 103 studies, we categorised COVID-19 molecular assays into 12 different test classes, covering point-of-care tests, various alternative RT-PCR protocols, and alternative methods such as isothermal amplification. We carried out meta-analyses to estimate the diagnostic accuracy and clinical utility of each test class. We also estimated the positive and negative predictive values of all diagnostic test classes across a range of prevalence rates. Using previously validated RT-PCR assays as a reference standard, 11 out of 12 classes showed a summary sensitivity estimate of at least 92% and a specificity estimate of at least 99%. Several diagnostic test classes were estimated to have positive predictive values of 100% throughout the investigated prevalence spectrum, whilst estimated negative predictive values were more variable and sensitive to disease prevalence. We also report the results of clinical utility models that can be used to determine the information gained from a positive and negative test result in each class, and whether each test is more suitable for confirmation or exclusion of disease. Our analysis suggests that several tests exist that are suitable alternatives to standard RT-PCR and we discuss scenarios in which these could be most beneficial, such as where time to test result is critical or, where resources are constrained. However, we also highlight methodological concerns with the design and conduct of many included studies, and also the existence of likely publication bias for some test classes. Our results should be interpreted with these shortcomings in mind. Furthermore, our conclusions on test performance are limited to their use in symptomatic populations: we did not identify sufficient suitable data to allow analysis of testing in asymptomatic populations.

BackgroundStudies on long COVID differ in the selection of symptoms used to define the condition. We aimed to assess to what extent symptom selection impacts prevalence estimates of long COVID. MethodsIn a prospective cohort of patients who experienced mild to critical coronavirus disease 2019 (COVID-19), we used longitudinal data on the presence of 20 different symptoms to evaluate changes in the prevalence of long COVID over time when altering symptom selection. ResultsChanging symptom selection resulted in wide variation in long COVID prevalence, even within the same study population. Long COVID prevalence at 12 months since illness onset ranged from 39.6% (95%CI=33.4-46.2) when using a limited selection of symptoms to 80.6% (95%CI=74.8-85.4) when considering any reported symptom to be relevant. ConclusionsComparing the occurrence of long COVID is already complex due to heterogeneity in study design and population. Disparate symptom selection may further hamper comparison of long COVID estimates between populations. Harmonised data collection tools could be one means to achieve greater reproducibility and comparability of results.

IntroductionThe Dutch recommendation on infection prevention and control (IPC) staffing in acute care hospitals from 2007 is outdated due to evolving hospital care, including shorter admissions, more complex and day-care procedures, more vulnerable patients, increasing antimicrobial resistance, and enhanced regulatory demands. Therefore, an updated staffing norm for IPC is needed. MethodsMinimum weekly hours required for IPC activities was determined by Delphi method across three model hospitals: academic, large non-academic, and small non-academic. Four questionnaire rounds were conducted among IPC practitioners (IPCP) and clinical microbiologists (CM). Staffing needs per role and hospital type were calculated. After three rounds a core expert team focus group formulated a new full time equivalent (FTE) norm which was proposed in the final round. ResultsFor academic hospitals, 100% consensus was achieved for a minimum of 0.15 FTE CM and 1.23 FTE IPCP per 5000 annual hospital admissions, plus 0.05 FTE CM and 0.41 FTE IPCP per 5000 annual day admissions, respectively. For non-academic hospitals, 92% supported the proposed norm for CM (same values), and 89% agreed with the proposed norm for IPCP: 1.10 FTE per 5000 hospital admissions and 0.37 FTE per 5000 day admissions. ConclusionA new consensus-based staffing norm, endorsed by most Dutch IPC professionals, recommends an increase in IPCP. This reflects increased demands on IPC teams and suggests diversification of professionals working in IPC teams, not accounted for in the previous norm. This minimum norm is needed to effectively protect patients and healthcare workers from infections.

BackgroundWith the introduction of metagenomics in clinical diagnostics unfolding and the expanding role of pathogen genomics in national surveillance, the stage is set for its launch into public health surveillance. This report pilots the use of metagenomics for nationwide sentinel general practitioner (GP) monitoring and genomic characterisation of both anticipated and emerging respiratory viruses in primary care. MethodsThis prospective pilot study included a selection of 93 patients with acute respiratory illness in GP practices participating in nationwide sentinel virological surveillance during winter 2024-2025. Specimens underwent parallel metagenomic testing using probes targeting human and animal viruses. The primary outcome was detection and in-depth genomic characterisation of viruses covered by standard screening and those outside the scope of standard methods. FindingsMetagenomic surveillance detected viruses in 95% of the specimens, including latent ones. Overall, 83% of specimens were positive by standard PCR-based screening. For viruses targeted by routine PCR, metagenomics showed a sensitivity of 94% (95%CI 86-97), specificity of 100% (95%CI 99-100), positive predictive value of 96% (95%CI 89-99), and negative predictive value of 100% (95%CI 99-100), with median genome coverage of more than 99% (95%CI 23-100%). Metagenomic data enabled instant full genomic characterisation of circulating viruses targeted by current amplicon-based surveillance, including influenza viruses, SARS-CoV-2, and respiratory syncytial viruses (RSV), as well as less frequently targeted viruses such as human metapneumoviruses (hMPV), betacoronaviruses OC43 and HKU1, and non-targeted viruses such as adenoviruses. The data facilitated characterisation of a reassortant H3N2 influenza virus, potential vaccine escape mutants, markers of susceptibility to influenza antiviral drugs and RSV monoclonal antibodies, and a human H1N2 swine influenza virus infection, demonstrating comprehensive and robust performance regardless of the circulating viruses. InterpretationIn this pilot study, metagenomic data enhanced standard typing through its broad scope and simultaneous detection and genome characterisation, enabling drug and vaccine resistance monitoring. These capabilities support the potential of metagenomics to expand current diagnostic approaches and gradual integration into public health surveillance. FundingThe Netherlands Organisation for Health Research and Development (ZonMw), and Ministry of Health, Welfare and Sport (VWS). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo identify studies using metagenomics for screening of patients with infectious diseases, we searched PubMed using the following search terms in the title/abstract: (metagenomic OR metagenomics OR mNGS) AND (prospective OR trial OR RCT). The results were filtered for prospective studies involving humans and written in English. The search was performed on December 10, 2025. The search results showed an exponential growth of prospective clinical studies on metagenomics, from only a few publications in 2021 to over 90 reports up to end-2025. The typical setting was diagnostic testing in hospitalised patients, and the primary focus of clinical performance assessment was detection as a dichotomous outcome rather than full genome characterisation. Around 80% of all prospective studies were observational: while sampling was prospective, metagenomic results were not reported in real-time as part of the study. One prospective study focused on respiratory metagenomic testing of outpatients in a public health setting. The study explored the use of untargeted metagenomics in Swiss outpatients, comparing COVID-19 pre-pandemic and pandemic periods, with retrospective reporting. This comparative study was limited to detection while the untargeted metagenomic approach did not demonstrate full genome characterisation. A recent News report in this journal announced the launch of the UK metagenomic Surveillance Collaboration and Analyses Programme (mSCAPE) for winter 2025-26, leveraging clinical metagenomic data from diagnostic laboratories in hospitalised patients for surveillance purposes. To our knowledge, no pilot results from this initiative have been reported to date. Added value of this studyThese data represent the first on the performance and feasibility of metagenomic surveillance integrated within the existing nationwide primary care sentinel GP infrastructure for genomic virological surveillance of acute respiratory infections. By performing viral detection and providing simultaneous full genome consensus sequences, typing of all circulating respiratory pathogens, as well as antiviral reduced susceptibility and antibody escape mutation analyses, could be performed directly. Prospective inclusion and metagenomic analyses were conducted in parallel with standard analyses and reporting to GPs and national and international stake holders. Although the metagenomic data delayed virus detection reporting compared to the standard approach, it outperformed standard surveillance sequencing by enabling full genome characterisation of all circulating viral pathogens, highlighting its potential in sentinel GP surveillance of acute respiratory infections. Implications of all the available evidenceEvidence is emerging that metagenomic approaches are effective and feasible for implementation not only in the clinical diagnostic setting but also for genomic characterisation in outpatient public health settings.

BackgroundRSV is a leading cause of ARI, including CAP, in older adults, but available data often substantially underestimate incidence. We estimated RSV-related ARI hospitalization incidence from a prospective CAP study and adjusted for undiagnosed RSV infections due to use of nasopharyngeal/nasal swab testing only. MethodsWe conducted active, population-based surveillance of adult CAP hospitalizations in Thuringia (Germany) between 2021-2023. Participant nasopharyngeal/nasal swabs were RSV-tested by multiplex nucleic acid amplification testing. To estimate RSV-related CAP incidence, age-group specific proportions of RSV positivity among tested patients were applied to all-cause CAP incidence. To adjust for underdiagnosis due to nasopharyngeal/nasal swab sampling only and the percentage of ARI with pneumonia diagnoses, we used data from a large, prospective, multispecimen study assessing impact of collecting multiple specimens (nasopharyngeal/nasal swab, saliva, paired serology, and sputum) among 3,669 adults hospitalized for ARI. ResultsAmong 1,040 enrolled adults ([&ge;]18 years) with radiologically confirmed CAP, 38 tested RSV-positive via nasopharyngeal/nasal swab (3.7%). The percentage positive increased to 7.8% after adjusting for higher RSV detection with multiple specimens compared to nasopharyngeal/nasal swab only. Adjusted RSV-related CAP hospitalization rates were 4.7 (95%CI 1.5-11.2) and 109.1 (95%CI 89.6-131.6) per 100,000 adults aged 18-59 and [&ge;]60 years, respectively. Adjusted incidences of RSV-related ARI were 18.4 (95%CI 11.0-28.9) and 377.6 (95%CI 340.5-417.7) per 100,000 adults aged 18-59 and [&ge;]60 years, respectively. Among RSV-positive CAP hospitalizations, 12.1% of patients aged [&ge;]65 years died within 30 days, with no deaths in those aged 18-64 years. Cardiovascular events occurred in 11.1% of patients aged 18-64 and 36.4% of those aged [&ge;]65 years. ConclusionsOlder adults in Germany face a high burden of RSV-related ARI hospitalizations, including CAP, underscoring RSV vaccinations potential utility for this population. KEY PUBLIC HEALTH MESSAGEO_ST_ABSWhat did you want to address in this study and why?C_ST_ABSHospital administrative data significantly underestimate respiratory syncytial virus (RSV) incidence due to infrequent testing and lower sensitivity of single nasopharyngeal/nasal swab testing among adults. No prospective incidence studies are available for Germany and most other European countries. We aimed to estimate RSV-related acute respiratory infection (ARI) hospitalization incidence from a prospective community-acquired pneumonia (CAP) study and adjust for undiagnosed RSV infections due to limited testing and use of nasopharyngeal/nasal swab testing only. Detailed data on RSV disease burden are crucial for developing vaccination policies. What have we learnt from this study?Adjusted annual incidence of RSV-related ARI rates were 18.4 (95% CI 11.0-28.9) and 377.6 (95% CI 340.5-417.7) per 100,000 population for adults 18-59 and [&ge;]60 years, respectively. Among RSV-positive CAP hospitalizations, 12.1% of patients aged [&ge;]65 years died within 30 days, with no deaths in those aged 18-64 years. Cardiovascular events occurred in 11.1% of patients aged 18-64 and 36.4% of those aged [&ge;]65 years. What are the implications of your findings for public health?Our findings are similar to recent time-series incidence results from Germany (236-363/100,000 for adults [&ge;]60 years) and underscore the substantial burden of RSV among adults, particularly the high rate of cardiovascular events contributes to a probably underestimated burden of RSV disease.

BackgroundPenicillin allergy labels are common and are often inaccurate. These labels can lead to unnecessary use of second-line non-beta-lactam antibiotics, and worse clinical outcomes. ObjectivesWe measured the impact of the introducing of a standardized proactive penicillin allergy de-labelling program with oral amoxicillin challenge on subsequent antibiotic use. MethodsWe performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses across two penicillin de-labelling intervention periods. Outcomes included data including penicillin allergy label and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics as well as multivariate regression analyses were performed. ResultsA total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention group sustained penicillin allergy label at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs 15 [7.7%], p= 0.04) and for only those patients who received antibiotics (28/46 [60.9%] vs. 15/40 [37.5%], p=0.097). In a multivariate analysis, the intervention was found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95% CU 1.29-5.02) and in those prescribed at least one antibiotic (OR 2.44, 95% CI 1.00-6.15). There were no differences in overall antibiotic prescribing by intervention and non-intervention group during admission (113 [64.9%] vs. 112 [57.7%]) or within 6-months (46 [26.4%] vs. 40 [20.6%]). No drug related adverse events were reported. ConclusionsProactive penicillin allergy de-labelling for inpatients was associated with a reduced number of penicillin allergy labels and increased utilization of beta-lactam vs. other antibiotics in the subsequent 6-months. Capsule SummaryA proactive systematic approach to antibiotic allergy de-labelling for inpatients with penicillin allergy label results in an increased number of patients de-labelled at hospital discharge and increased beta-lactam use in the subsequent 6 months.

Surveillance of acute lower respiratory tract disease (aLRTD) is fundamental for understanding population health burden and healthcare needs. COVID-19 altered the epidemiology of respiratory infections, but post-pandemic aLRTD incidence and severity remain underexplored in the UK. We conducted a prospective cohort study of adults ([&ge;]18 years) admitted to two Bristol hospitals (August 2020-July 2024) with symptoms or a diagnosis of pneumonia, non-pneumonic lower respiratory tract infection (NP-LRTI), or no evidence of LRTI. Of 457,112 hospitalizations, 44,792 (9.8%) were due to aLRTD: 48.2% pneumonia, 35.2% NP-LRTI, and 16.7% no LRTI. Incidence peaked in 2021-22 (14.4/1,000 person-years) due to COVID-19 before stabilizing around 13.6. SARS-CoV-2 pneumonia declined; non-COVID pneumonia remained stable. Mortality risk was lower for NP-LRTI (HR 0.32) and no LRTI (HR 0.43) compared to pneumonia. Older age and comorbidities increased mortality. Non-COVID infections persisted despite interventions, emphasizing the need for surveillance and vaccination in public health planning.

Perioperative anaphylaxis (POA) is a severe complication with a low incidence and diverse risk factors. Its low incidence makes a detailed survey of POA challenging. Recent large-scale surveys in Japan have focused on identifying the causative agents using the basophil activation test. Only facilities, such as university hospitals, that can dispatch samples for this test participate, which may introduce bias. We surveyed the incidence of POA primarily in secondary hospitals, such as the Saiseikai hospitals, throughout Japan. We targeted data collection for the year 2021. Thirty-five facilities answered (Supplementary 1, 2); we excluded 1 reporting no surgeries. In total, 70,523 surgeries were performed, with POA diagnosed in 7 cases. For diagnosis, the skin test was used in 3 cases and quantification of histamine and tryptase in 1 case. In 3 cases, diagnosis was based on the time to onset of POA after drug use. Multiple tests are important to ensure patient safety. However, in this survey, no hospital performed in vitro tests to identify the cause. This is major limitation, however, as many hospitals do not have experimental laboratories, we believe that this study, which focuses on secondary care institutions, contributes to the literature significantly by presenting the current situation in clinical practice.

BackgroundLower respiratory tract infections (LRTIs) remain a major cause of morbidity and mortality among hospitalized patients.1 However, isolating organisms from respiratory samples often leads to diagnostic uncertainty due to the coexistence of colonizers, commensals, and contaminants.2 To address this challenge, this study employed a structured, stepwise exploratory model to differentiate true pathogens from non-pathogens in aerobic respiratory cultures and Multiplex PCR (Biofire(R) FilmArray) results. MethodsThis prospective, longitudinal time-bound study was conducted over three months (August- October 2024) at a tertiary care center in northern India. Adult patients ([&ge;] 18 years) with positive lower respiratory tract samples (aerobic culture or Multiplex PCR (Biofire(R) FilmArray) were enrolled. Each isolate was independently classified by the treating clinician, microbiologist, and study investigator using a six-step clinical-pathological algorithm that incorporated clinical signs, Sequential Organ Failure Assessment (SOFA) score trends, alternative infection sources, host factors, and outcome data. The final classification was determined by the investigator. Outcomes, including treatment response and mortality at 28 days, were compared across pathogen and non-pathogen groups. FindingsOf the 145 included cases, 131 (90{middle dot}3%) were classified as pathogens and 14 (9{middle dot}7%) as non-pathogens. Cohens Kappa between investigator and microbiologist classifications was 0{middle dot}28, indicating fair agreement. Among pathogen cases, 68 (51{middle dot}9%) responded to treatment, while 63 (48{middle dot}1%) did not respond to treatment in the pathogenic group. In contrast, 12 of 14 non-pathogen cases (85{middle dot}7%) were not treated, with favourable outcomes in most, and only one unrelated death (7{middle dot}1%). InterpretationThe structured clinico -microbiological model strongly correlates with treatment outcomes, making it useful for differentiating infection from colonization. Crucially, microbiological detection alone doesnt determine pathogenicity. Integrating clinical, laboratory, and outcome data is essential for rational antibiotic use and effective antimicrobial stewardship. FundingNone

BackgroundThe COVID-19 pandemic caused by the SARS-CoV-2 virus greatly affected healthcare workers and healthcare systems. It also challenged schools and universities worldwide negatively affecting in-person education. We conducted this study is to assess the evolution of SARs-CoV-2 virulence over the course of the pandemic. MethodsA combined cohort of affiliates from the University of Navarra, two hospitals in Spain, and one healthcare system in the Greater Boston area was followed prospectively from March 8th, 2020, to January 31st, 2022 for diagnosis with COVID-19 by PCR testing and related sequelae. Follow-up time was divided into four periods according to distinct waves of infection during the pandemic. Severity of COVID-19 was measured by case-hospitalization rate. Descriptive statistics and multivariable-adjusted statistics using the Poisson mixed-effects regression model were applied. ResultsFor the last two periods of the study (January 1st to December 15th, 2021 and December 16th, 2021 to January 31st, 2022) and relative to the first period (March 8th to May 31st, 2020), the incidence rate ratios (IRRs) of hospitalization were 0.08 (95% CI, 0.03-0.17) and 0.03 (95% CI, 0.01-0.15), respectively. InterpretationThe virulence of COVID-19 and immunity of our populations evolved over time, resulting in a decrease in case severity. We found the case-hospitalization rate decreased more than 90% in our cohort despite an increase in incidence.

BackgroundThere are financial relationships between healthcare professionals and pharmaceutical companies, and these relationships have historically caused conflicts of interest and unduly influenced patient care. However, little was known about such relationship and its effect in clinical practice among specialists in respiratory medicine. MethodsBased on the retrospective analysis of payment data made available by all 92 pharmaceutical companies in Japan, this study evaluated the magnitude and trend of financial relationships between all board-certified Japanese respiratory specialists and pharmaceutical companies between 2016 and 2019. Magnitude and prevalence of payments for specialists were analyzed descriptively. The payment trends were assessed using the generalized estimating equations for the payment per specialist and the prevalence of specialists with payments. ResultsAmong all 7,114 respiratory specialists certified as of August, 2021, 4,413 (62.0%) received a total of USD($) 53,547,391 and 74,195 cases from 72 (78.3%) pharmaceutical companies between 2016 and 2019. The mean{+/-}SD and median (interquartile range) four-year combined payment values per specialist were $12,134{+/-}$34,045 and $2,210 ($715{square}$8,178) respectively. At maximum, one specialist received $495,332 personal payments over the four years. Both payments per specialist and prevalence of specialists with payments significantly increased during the four-year period, with 7.8% (95% CI: 5.5{square}9.8; p<0.001) in payments and 1.5% (95% CI: 0.61% {square}2.4%; p = 0.001) in prevalence of specialists with payments, respectively. ConclusionMajority of respiratory specialists had increasingly received substantial personal payments from pharmaceutical companies for the reimbursement of lecturing, consulting, and writing between 2016 and 2019. These increasing financial relationships with pharmaceutical companies might cause conflicts of interest among respiratory physicians.

ObjectiveThis study utilizes small-sample periodontitis data to exploratively investigate causal relationships between the oral microbiome and periodontitis in East Asian populations. We aimed to identify specific oral microbial taxa that may drive disease pathogenesis. Given the exploratory nature of the dataset, findings should be interpreted as hypothesis-generating. MethodsWe performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics for tongue dorsum and salivary microbiomes alongside periodontitis data in East Asian populations. Primary causal estimates were derived using the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode methods. To ensure robustness, we assessed heterogeneity using Cochrans Q test, evaluated horizontal pleiotropy via the MR-Egger intercept and MR-PRESSO tests, and applied Steiger filtering to rule out reverse causality. ResultsWe identified 60 species-level microbial taxa causally associated with periodontitis, comprising 29 negative and 31 positive associations. These taxa were predominantly enriched within the genera Campylobacter, Pauljensenia, Solobacterium, and Streptococcus. ConclusionThis study provides tentative evidence for causal links between specific species-level oral microbial taxa and periodontitis, highlighting potential targets for prevention and therapeutic intervention.