Infectious Diseases and Therapy

Clesrovimab and nirsevimab are long-acting monoclonal antibodies used to prevent respiratory syncytial virus (RSV) disease in infants, but waning protection in the first year of life is incompletely characterised. We applied a published Bayesian inference framework to clesrovimab and pooled nirsevimab trial data to estimate time-varying efficacy against medically attended RSV lower respiratory tract infection (LRTI) and RSV-associated hospitalisation, accounting for differences in placebo-arm event timing between trials. Estimated clesrovimab efficacy declined from 60.7% (95% CrI: 46.3-72.6) shortly after dosing to 38.3% (8.6-52.9) at six months against medically attended RSV LRTI, and from 87.1% (71.2-96.2) to 49.6% (10.4-70.7) against RSV-associated hospitalisation. For nirsevimab, corresponding estimates declined from 86.9% (75.4-95.0) to 53.8% (27.4-69.7) against LRTI, and from 77.5% (52.6-91.8) to 49.7% (15.7-68.3) against hospitalisation. After accounting for differences in RSV exposure timing and LRTI endpoint definitions between trials, we found no evidence of a difference in efficacy or waning between clesrovimab and nirsevimab.

Introduction: Respiratory syncytial virus (RSV) causes significant disease in older and comorbid adults. Current UK vaccination recommendations restrict eligibility to adults [&ge;]75-years, 65-74-years with chronic respiratory disease or immunosuppression, and those in care homes, but evidence on clinical burden in adults <75-years with comorbidities is limited. This study assessed patient characteristics, healthcare resource utilisation (HCRU), and mortality in adults hospitalised with RSV in England. Methods: Population-based retrospective cohort study using linked Clinical Practice Research Datalink Aurum and Hospital Episode Statistics. Adults [&ge;]60-years hospitalised with RSV between October 2014-March 2019 were included. RSV episodes defined as 90-days post diagnosis. Case definitions were created using diagnosis codes related to confirmed RSV (RSV-specific) or acute lower respiratory tract infection where other causative pathogens were excluded (RSV-possible). All-cause HCRU (hospitalisations, critical care admissions, outpatient attendance, primary care consultations, and prescriptions) and case fatality rates were assessed. Results were stratified by age (60-74 and [&ge;]75-years), case definitions (RSV-specific, RSV-possible) and comorbidity profiles (chronic respiratory disease, immunocompromised, cardiovascular disease). Results: A total of 97,712 hospitalised episodes in those aged [&ge;]60-years were included in the analysis, where 785 (0.8%) were RSV-specific cases (n=338 aged 60-74-years, n=447 aged [&ge;]75-years). In RSV-specific cases, median (IQR) cumulative length of stay (LoS) for those [&ge;]75-years was 10.00 (6.00-22.00) days which was equivalent to or lower than each comorbidity sub-group in those aged 60-74-years, with longest LoS in those immunocompromised (11.50 [7.00-26.00] days). Critical care admissions were more often observed across comorbidity stratifications (13.85%-22.34%) compared to those [&ge;]75-years (5.03%). All-cause and RSV-related case fatality rates for RSV-specific cases were highest among those [&ge;]75-years (all-cause: 19.3%; RSV-related: 10.3%). Conclusion: HCRU within RSV episodes in those aged 60-74-years across comorbidity profiles was equal to or greater compared to those aged [&ge;]75-years. These findings highlight the need to prioritise consideration of comorbidity groups that could benefit from RSV vaccination. Key words: Respiratory syncytial virus; vaccine; chronic obstructive pulmonary disease; diabetes mellitus; immunocompromised; asthma; chronic kidney disease; cardiovascular disease; healthcare resource utilisation.

Long COVID (LC) is a broad label encompassing the heterogeneous long-term consequences of SARSCoV2 infection that persist for at least 3 months post-infection. Despite its substantial global burden, there is still a lack of reliable biomarkers or panels capable of distinguishing individuals with Long COVID from healthy individuals or from those who have recovered from acute COVID-19. We previously characterized a biomarker panel comparing 85 adults with WHO-defined Long COVID against 85 age- and sex-matched controls who had recovered within three months of acute COVID-19 in 2020, at between 12 and 24 months post-infection. That initial profile evaluated blood cell counts, coagulation status, routine SARS-CoV-2 serology, immune cell populations, and basic cytokine levels based on Luminex assays. We have enhanced our biomarker panel by incorporating more precise cytokine quantification using the high-precision ELLA automated immunoassay system. To assess potential ongoing peripheral systemic inflammation, we measured classical inflammatory markers in blood, including C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha), interleukin (IL)1beta, and IL6. In this manuscript, we present data that confirm age- and gender-matching between the LC and control group; and compared differences in cytokine levels and comorbidities.

Background: Monitoring Pseudomonas aeruginosa (P. aeruginosa) infection in people with cystic fibrosis (pwCF) is essential for early detection, targeted treatment, and prevention of chronification. Sputum culture is the current standard, yet many patients, particularly those receiving CFTR modulator therapy, struggle to expectorate sputum. Microbial aerosols from the respiratory tract offer a non-invasive alternative. This proof-of-principle study assessed the accuracy and feasibility of the AveloMask, a novel breath aerosol collection kit paired with qPCR detection. Methods: Adult pwCF and bronchiectasis patients attending routine monitoring visits and healthy controls were enrolled in a cross-sectional study. Participants wore the mask for 30 minutes, followed by 20 instructed coughs. Mask filters were tested with a triplex qPCR assay targeting P. aeruginosa specific ecfX and gyrB, and human RPP30 as an endogenous control. Accuracy was evaluated using a composite reference standard (sputum culture and PCR). Results: Of 25 patients enrolled, 23 were included in the analyses. Sensitivity was 12/19 (63.2%) for breath qPCR versus 15/19 (78.9%) for sputum culture. Breath qPCR missed 5 cases detected by sputum culture but detected 2 sputum culture-negative/qPCR-positive cases. Specificity of breath qPCR was 100% in 4 patients and 15 healthy controls. RPP30 was detected in all mask samples. AveloMask was perceived as easy to use, with many patients preferring it over sputum collection. Discussion: Mask-based breath collection demonstrated promising diagnostic accuracy for detection of P. aeruginosa. Breath sampling may complement or partially substitute sputum-based diagnostics, especially in patients unable to expectorate. Further studies are needed to define its clinical role.

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents [&le;]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days.

Background: Longer follow-up periods in clinical trials for S. aureus bacteremia (SAB) may capture unrelated deaths, adding random noise that risks biasing trial results towards the null. Objective: To evaluate the timing and infection-relatedness of deaths within a large SAB clinical trial platform. Design: Blinded duplicate adjudication of trial deaths using a modified 7-point Likert-Scale. A third reviewer settled disagreements. Setting: 37 Canadian hospitals participating in the S. aureus Network Adaptive Platform (SNAP) Trial. Participants: 1515 adult patients recruited to SNAP between February 2022 and May 2026. Measurements: Timing and relatedness of 90-day deaths categorized as at least possibly SAB-related not likely to be SAB-related. Optimal follow-up cut-off was determined using Youden's index and graphically. Results: 247 deaths occurred; 97 (39.3%) were adjudicated as at least possibly SAB-related and 150 (60.7%) as not likely related. For probably/definitely related deaths, interrater agreement was 85.0% (Gwet's AC 0.73, substantial); for at least possibly related, it was 77.3% (Gwet's AC 0.55, moderate). Median survival was significantly shorter for SAB-related deaths (12 vs. 30.5 days; difference: 19 days earlier, 95% CI: 12-26, p<0.0001). Nearly 80% of SAB-related deaths occurred by day 30, whereas 50% of unrelated deaths occurred between days 30 and 90. Youden's index optimized follow-up at 20.5 days. Limitations: Potential for cause of death misclassification and data limited to Canadian sites. Conclusion: Deaths considered attributable to SAB cluster rapidly within the first month, while later deaths are predominantly unrelated. A 30-day all-cause mortality window may be more appropriate than 90 days for primary mortality outcomes in trials evaluating acute SAB therapies with longer follow up reserved for metastatic infection and recurrence.

Background: Invasive pulmonary aspergillosis (IPA) is a serious infection in critically ill patients. Galactomannan detection in endotracheal aspirates (ETA) has emerged as a promising non-invasive diagnostic method. This study evaluates the supportive diagnostic value of ETA galactomannan in ICU patients suspected to have IPA. Methods: We conducted a prospective observational cohort study over two years, enrolling 120 patients in the medicine ICU at a tertiary care centre in India (January 2022 to October 2023). Patients aged over 14 years on mechanical ventilation for >48 hours meeting the entry criteria of the BM-AspICU algorithm were included. ETA galactomannan was measured and correlated with IPA classification. Results: Of 120 patients, 37% (n=44) had probable IPA and 63% (n=76) were classified as colonisers or possible IPA. The optimal ETA galactomannan cut-off was 1.097, yielding sensitivity 72.73% (95% CI 57.2 - 85.0%), specificity 84.2% (95% CI 74.4 - 90.7%), PLR 4.86, NLR 0.35, and AUC 0.844 Conclusion: ETA galactomannan supports IPA diagnosis with favourable sensitivity and specificity. However, given the limitations of clinical scoring-based reference standards and the potential plateau in colonizer reduction at higher cut-offs, it should be integrated into a comprehensive diagnostic approach incorporating clinical, radiological, and microbiological criteria.

Objective: Treatment of acute COVID-19 with anti-viral and immunomodulator medications demonstrates a reduced risk of long-term outcomes. To date, remdesivir, an intravenous (IV) antiviral that prevents RNA transcription, has not been evaluated in people with Long COVID (LC). This study assessed the feasibility of a five-day IV remdesivir intervention for individuals with LC. Methods: Seventy-three participants aged [&ge;]18 years with a confirmed LC diagnosis were recruited across two sites in the United Kingdom to receive a five-day course of IV remdesivir. Primary feasibility outcomes included recruitment, treatment completion, acceptability, and safety. Exploratory patient-reported (e.g. Fatigue Assessment Scale [FAS]) and clinical outcomes (e.g. 6-minute walk test [6MWT]) were also collected. Results: Of 106 individuals screened, 73 were enrolled and 71 (97%) completed the 5-day IV remdesivir regimen. Follow-up assessments were completed by 70 participants (96%), with high completion rates observed across clinical assessments, patient-reported outcomes and symptom tracking. No severe adverse reactions were reported. Improvements were also observed in several exploratory patient-reported and clinical outcomes. Conclusion: We demonstrated the feasibility and acceptability of administering IV remdesivir in people with LC. Analysis of secondary outcomes suggests therapeutic promise, but rigorous evaluation in large-scale randomised controlled trials is essential to determine the true efficacy and clinical utility of intravenous remdesivir in this population.

Seasonal influenza remains a major cause of morbidity and mortality worldwide. Although neuraminidase inhibitors improve outcomes, influenza-related deaths persist. We evaluated the impact of early aspirin (ASA) and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use on outcomes in adults hospitalized with influenza. This retrospective study included adults admitted to the University of Minnesota Medical Center from 2016 to 2018. Continuous variables were summarized as medians with interquartile ranges (IQRs) and categorical variables as counts and percentages. Group comparisons used Wilcoxon rank-sum, Chi-square, or Fishers exact tests. Analyses included case-control comparisons, assessments by vaccination status, and subgroup analyses by early ASA or NSAID use. Among 2,816 patients, 320 had laboratory-confirmed influenza, with vaccination less common among cases. Unvaccinated patients had higher rates of intensive care unit (ICU) admission (23.6% vs. 11.1%; P = 0.003) and ventilatory support (15.0% vs. 6.1%; P = 0.009). In vaccinated patients, early ASA use was associated with older age and higher in-hospital mortality, whereas early NSAID use was associated with no in-hospital deaths, better one- and three-year survival (P < 0.001), and fewer, though not statistically significant, cardiovascular complications. In unvaccinated patients, ASA use was associated with lower three-year survival (59.1% vs. 79.2%; P = 0.013), while NSAID use was associated with fewer ICU admissions and no cardiovascular or renal complications. In both vaccinated and unvaccinated adults hospitalized with influenza, early NSAID use was associated with improved survival and fewer complications, whereas ASA use was associated with worse outcomes.

Background and Aims The optimal treatment for first episodes and first recurrences of Clostridioides difficile infections (CDI) is unknown and there is emerging evidence for pulse and taper (P-T) regimens. Therefore, we sought to estimate the relative efficacy of treatment options. Methods MEDLINE and CENTRAL were searched from database inception to May 21, 2025 and unpublished conference abstracts were searched from recent infectious disease conferences. RCTs on the treatment of first episodes or first recurrences of CDI comparing fixed-dose or P-T regimens of fidaxomicin or vancomycin were included. The primary and secondary outcomes were 40- and 56-day CDI recurrence, respectively. A random-effects network meta-analysis on the risk ratio (RR) scale was conducted using a standard regimen (10-14 days) of vancomycin as the comparator. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results 8 RCTs were included comprising a total of 2181 patients. For 40-day recurrence, fidaxomicin P-T had the highest probability of ranking best (RR=0.10, 95%Confidence Interval [95%CI]=0.10-0.49, SUCRA=1.00), followed by vancomycin P-T (RR=0.49, 95%CI=0.32-0.76, SUCRA=0.61), fixed-dose fidaxomicin (RR=0.61, 95%CI=0.49-0.76, SUCRA=0.39), and, finally, fixed-dose of vancomycin (SUCRA=0.00). The treatments ranked in the same order for 56-day recurrence, though only 3 RCTs reported on this timepoint. Conclusion Vancomycin P-T, fidaxomicin P-T, and fixed-dose fidaxomicin were all superior to a fixed-dose vancomycin. Head-to-head comparative effectiveness RCTs are needed to quantify their relative effect sizes of and impact on long-term prevention of recurrent CDI.

Objectives: Large language models (LLMs) are increasingly used in medicine, but evaluation is often on multiple choice questions and management of common conditions. Infectious diseases (ID) can present complex scenarios that require considerations beyond guideline-based responses. We assessed LLM performance in these situations including with ID-specific criteria to consider infection control or antimicrobial stewardship (AMS). Methods: We evaluated four LLMs (Claude 3.5 Sonnet, GPT-4o, GPT-o1, and a local instance of Llama 3.1 8B) in October 2024, on five complex ID vignettes. The LLM responses were each evaluated for 18 items by two board-certified ID clinicians and pairwise comparisons were performed between LLMs. Results: There was no significant difference between performance of GPT-o1, GPT-4o and Claude Sonnet on general medical criteria, and were comparable with respect to how often they provided an unsafe response (GPT-o1 30%, GPT-4o 40%, Claude 37%) and contained a critical omission (GPT-o1 27%, GPT-4o 43%, Claude 47%). Llama 3.1 8B had significantly decreased performance for most criteria. On ID-specific criteria, GPT-o1 outperformed other models and all models significantly outperformed Llama for interpreting microbiology results, AMS principles, appropriate antimicrobial spectrum and infection control considerations. Performance was poor in secondary prevention and management of risk factors. Conclusions: On complex ID scenarios, LLM responses were variable. The open-source, smaller Llama 3.1 8B model performed poorly and large, non-reasoning models varied, but more than 30% of responses containing a risk of harm or critical omission. These findings suggest caution is required when deploying these models in ID domains without specialist oversight.

Background Bloodstream infections are a major cause of mortality, yet the primary testing method, blood cultures, have low positivity (<10%) and turnaround times of 24 - 48 hours. Many are taken from patients at low risk of infection, while some bloodstream infections are diagnosed late or missed entirely. We aimed to develop and externally validate machine learning models to improve targeting of blood culture testing. Methods In this retrospective cohort study, we used routinely collected clinical and laboratory data available around culture collection from a large multi-site NHS trust (Oxford University Hospitals; Infections in Oxfordshire Research Database), between 1 January 2016 and 17 March 2025. All blood cultures taken from adults and children were included. XGBoost models were trained to predict pathogenic blood culture positivity using a temporal split (training before 1 January 2024; held-out test thereafter). External validation used emergency department data (between 1st May 2019 and 30th April 2024) from University College London Hospitals. An additional analysis examined blood culture reallocation towards the highest-risk untested admissions. Findings 294,064 cultures were included (positivity 5.6%). In the temporal hold-out test set (n=46,339), AUROC (Area Under the Receiver Operating Characteristic) was 0.853 (95% CI 0.846 - 0.860), rising to 0.876 in emergency department patients, and the model was well calibrated (slope 1.046). In external validation (n=37,326), AUROC was 0.847 (95% CI 0.839 - 0.856) with preserved calibration. In a simulated resource-neutral reallocation, replacing the 10,000 lowest-risk sent cultures with the highest-risk untested emergency admissions yielded 627 additional positive cultures (28.3% relative increase in yield). Performance was reduced when restricted to data available at the point of culture collection (AUROC 0.769, 95% CI 0.760 - 0.779). Interpretation An externally validated, well calibrated machine learning model built from broadly available, routinely collected data could improve blood culture yield without increasing testing volume, supporting resource-neutral diagnostic stewardship across NHS sites.

Introduction: RSV vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least 2 RSV seasons following vaccination. No data have been published on real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination. This study evaluates bivalent RSVpreF VE against RSV-related lower respiratory tract disease (LRTD) hospitalizations/ED visits throughout 3 seasons after vaccination. Methods: This retrospective test-negative case-control evaluates bivalent RSVpreF VE among adults aged >/= 60 years at Kaiser Permanente Southern California with LRTD over 3 RSV seasons (11/24/20230-4/18/2026). Cases were RSV-positive without coinfection. Controls were negative for RSV, hMPV, influenza, SARS-CoV-2, and positive for a non-vaccine preventable disease pathogen. Exposure was bivalent RSVpreF (Abrysvo) receipt >/= 21 days before LRTD. Adjusted VE was estimated using odds ratios from multivariable logistic regression or generalized estimating equations. Results: Overall, adjusted VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI:68-87), 70% (95% CI:53-81), and 51% (95% CI:-12-78) in the first, second, and third season after vaccination, respectively. Among non-immunocompromised individuals, adjusted VE against RSV-related LRTD was 87% (95% CI:75-94), 76% (95% CI:55-87), and 58% (95% CI:-21-86) in the first, second, and third season after vaccination, respectively. Adjusted VE across the 3 combined seasons was 73% (95% CI: 64-80) overall and 80% (95% CI: 69-87) among non-immunocompromised individuals. Conclusion: These results suggest Bivalent RSVpreF provides protection against RSV-related LRTD outcomes for at least three seasons after vaccination in this population of older adults with a prevalence of comorbidities. This suggests RSV vaccination results in substantial individual and public health benefit.

Background: A maternal vaccine (MV) and a long-lasting monoclonal antibody (la-mAB) have been licensed to protect children against RSV. Given the swift waning of their protection, we evaluated the added benefit of seasonal la-mAB administration for children born to vaccinated mothers shortly after the RSV season in Germany. Methods: We fitted an age- and birth season-structured catalytic model to cross-sectional seroprevalence data of RSV antibodies using a Bayesian framework to estimate the timing of RSV infections in children <5. We then estimated the incidence of severe outcomes in the absence of immunisation in children <1. Finally, we estimated the impact of the MV and of additional la-mAB administration, accounting for the waning of protection. Results: We estimate that children would, on average, be 7 months old (mo) at their first infection, those born in the autumn being the youngest at first infection (4 mo). Together with the children born in the winter, they account for 46% of all RSV hospitalisations and 62% of RSV ICU admissions in unimmunised <1 yo. MV would prevent a total of 776 (473-1,122) hospitalisations per 100,000 vaccinees and 73 (51-94) ICU admissions per 100,000 vaccinees, predominantly among autumn-born children. The summer birth cohort would benefit most from additional la-mAB administration, preventing an additional 46% (10-63) of ICU admissions compared to MV alone, corresponding to an additional 25 (4-45) ICU admissions prevented per 100,000 immunised children. Conclusion: Compared to MV alone, the impact of MV+la-mAB on RSV hospitalisations and ICU admissions would likely be modest.

Importance: OPAT is an underutilized strategy in low- and middle-income countries (LMICs). Addressing the knowledge gaps among frontline physicians through structured interventions is vital for optimizing hospital bed utilization and antimicrobial stewardship. Objective: To assess whether a structured multidisciplinary care bundle is associated with improved patient enrollment and clinical care quality in an OPAT program in India. Design, Setting, and Participants: This pre-post quality improvement study was conducted in the Department of General Medicine at a tertiary care referral hospital in Rishikesh, India. Data from patient encounters during a 6-month pre-intervention period (December 1, 2023 to May 31, 2024) were compared with encounters during a 6-month post-implementation period (January 1, 2025 to June 31, 2025). Participants included all postgraduate residents serving as frontline clinical practitioners. Interventions: A structured OPAT bundle comprising a formalized educational curriculum (interactive didactic sessions and bedside practical training), standardized eligibility screening, and a coordinated telephonic monitoring protocol (from June 1, 2024 to December 31, 2024). Main Outcomes and Measures: The primary outcome was the change in the number of eligible patients enrolled in OPAT. Secondary outcomes included clinical process quality indicators (counseling, IV access arrangement, and monitoring compliance), 30-day rehospitalization rates, and therapy-related complications. Results: A total of 20 preintervention patient encounters were compared with 39 postintervention encounters, with similar baseline characteristics between groups (mean age, 37 vs 40 years; male gender, 65% vs 69.2%). Prior to implementation, only 33.3% (20 of 60) of eligible patients received OPAT, whereas 100% (39 of 39) of eligible patients were enrolled following the intervention (p < 0.001). Key clinical processes reached 100% compliance post implementation, including patient counseling (40% vs 100%; p < 0.001), pre-discharge IV access (40% vs 100%; p < 0.001), and daily telephonic monitoring (10% vs 100%; p < 0.001). Safety outcomes remained stable, with no significant differences in readmission rates (5.0% vs 0%; p = 0.34) or drug-related complications. Conclusions and Relevance: This quality improvement study provides evidence that a structured package of OPAT bundle interventions is associated with a transition to universal enrollment of eligible patients and perfect adherence to safety indicators. These results suggest that standardizing the outpatient transition through physician education and coordinated monitoring is a feasible and effective strategy for optimizing hospital resource utilization in LMICs.

Respiratory syncytial virus (RSV) contributes to substantial morbidity and mortality in young children each year. In 2023, two new prevention products were licensed and recommended in the United States (US), including a prefusion F protein subunit vaccine (RSVpreF) administered during pregnancy and a long-acting monoclonal antibody (mAb) administered in infants. Although post-licensure real-world studies support the effectiveness of RSVpreF vaccine during pregnancy, existing studies have been conducted in settings where only RSVpreF vaccine is available. The real-world effectiveness of RSVpreF vaccine in settings where both RSVpreF vaccine and mAbs are available is not yet well understood. The goal of this study is to estimate the real-world effectiveness of the RSVpreF vaccine against severe infant RSV by applying causal mediation analysis with receipt of mAbs as a mediating variable. Using a national cohort of mother-infant dyads with the Optum Labs Data Warehouse (OLDW), we will model vaccine and mAb effects in a longitudinal cohort spanning the 2023-24, 2024-25, and 2025-26 RSV seasons. Results will be used to better understand the total effect of RSVpreF vaccination when it is used as one component within a hybrid infant RSV prevention program.

Background: Localized skin and soft tissue infections may need systemic antibacterials, but local inflammation can delay symptom recovery. We evaluated whether topical fresh Taraxacum mongolicum wet dressing added to ceftriaxone was associated with short-term benefit in selected clinically stable adults. Methods: In this single-center, assessor-blinded, three-arm randomized trial, 180 adults aged 18-74 years were randomized 1:1:1 to topical T. mongolicum plus intravenous ceftriaxone, topical T. mongolicum alone, or ceftriaxone alone for 7 days. The primary outcome was day-7 clinical response assessed by blinded independent assessors using prespecified global clinical improvement criteria. Analyses followed the intention-to-treat principle; sensitivity analyses assessed robustness. Results: Day-7 clinical response rates were 91.67% (55/60), 76.67% (46/60), and 68.33% (41/60) in the combined, T. mongolicum, and ceftriaxone groups, respectively (overall P = 0.006). Compared with ceftriaxone alone, combined therapy had a higher response rate (risk difference, 23.3 percentage points; 95% CI, 9.6 to 37.0; risk ratio, 1.34; 95% CI, 1.11 to 1.62). Sensitivity analyses were directionally consistent. Secondary outcomes and bacterial clearance favored the combined group. No serious adverse events were reported. Conclusions: In selected clinically stable adults with localized skin and soft tissue infections, adjunctive topical fresh T. mongolicum plus ceftriaxone was associated with improved short-term outcomes compared with ceftriaxone alone. Findings require cautious interpretation because this was a single-center, partially blinded trial without a placebo dressing control. The dressing should not replace antibiotics, drainage, or urgent care when indicated. Trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR2026000549.

Background Otitis media is a leading cause of childhood morbidity and presents a significant healthcare burden worldwide. Streptococcus pneumoniae is a major aetiological agent of OM, and the introduction of pneumococcal conjugate vaccines into the Malaysian National Immunisation Programme in 2020 would have altered pneumococcal carriage and serotype distribution. This study aimed to determine pneumococcal carriage, serotype distribution, and associated risk factors among children with OM in the early post-PCV era in Peninsular Malaysia. Methods and Findings A total of 360 children with OM were recruited from hospitals on the east and west coasts of Peninsular Malaysia between 2023 and 2025. Nasopharyngeal and middle ear fluid samples were collected for Spn isolation by culture, followed by serotyping using multiplex PCR. Sociodemographic, environmental, and medical history data were analysed for associations with pneumococcal carriage using chi-square, Fishers exact tests, and logistic regression. Pneumococcal carriage was detected in 26.7% of children in either NP or MEF samples, with carriage rates of 25.6% and 1.9% in NP and MEF samples, respectively. The most prevalent serotypes were 23A, 15B/15C, non-typable strains, 19F, and 11A/11D. Daycare attendance (p = 0.012, aOR [95% CI]: 2.177 [1.186 - 3.995] and residence in rural areas (p = 0.019, aOR [95% CI]: 2.476 [1.159 - 5.292] were significantly associated with pneumococcal carriage. The main limitation of the study was the reliance on self-reported questionnaire data, which may have introduced recall bias and reporting errors. Conclusions The predominance of non-vaccine serotypes and non-typable Spn indicates ongoing serotype replacement and the emergence of phase-variant strains in the early post-PCV era. Continued surveillance is essential to monitor these changes and inform the development of next-generation pneumococcal vaccines. This study was registered under clinical trial registration number NCT05429541.

Objectives: Capturing adequate blood volume for blood cultures is critical for accurate detection of bloodstream infections. Pediatric volume targets vary by age and weight, whereas adult targets are standardized. The BD BACTEC FXI Culture System (FXI) contains an integrated calibrated load cell capable of automatically reporting blood volume measurements for each vial loaded onto the system. This study evaluated the accuracy of the FXI's blood volume measurements in simulated pediatric and adult patients. Methods: Mock pediatric and adult blood draws were performed, using bagged whole blood, to replicate real-world collection protocols. Syringe-collected blood volumes ranged from 2.0 to 15.0 mL for pediatric patients, depending on mock patient weight, and were fixed at 40.0 mL for adults. Samples were inoculated into BD BACTEC Peds Plus/F, Plus Aerobic/F, and Lytic/10 Anaerobic/F Culture Vials, with a target volume of 2.0 to 10.0 mL per bottle. Reference blood volumes were determined gravimetrically using manually obtained pre- and post-inoculation weights with a blood-specific gravity of 1.055 g/mL and were compared to the automatically measured, gravimetric-based blood volumes reported by the BACTEC FXI Culture System. Results: Automated volume estimates were accurate to a mean error of -0.03 mL per bottle (SD, 0.40 mL; n=168; 95% CI, -0.09 mL, 0.03 mL) and -0.08 mL (SD, 0.79 mL; n=72; 95% CI, -0.26 mL, 0.10 mL) when assessing total volume collected per patient. Conclusions: Our findings demonstrate that the automated system can quantify blood volumes in BACTEC culture vials and support blood volume monitoring for pediatric and adult collections. The gravimetric approach is also amenable to full automation for efficient and accurate blood volume determination.

Rationale. Guidelines disagree on antibacterial treatment for adults with community-acquired pneumonia and a positive respiratory viral test, particularly hospitalized patients and outpatients with comorbidities. Objectives. To estimate associations between antibacterial treatment selected for community-acquired pneumonia and outcomes in adults with virus-positive, imaging-evaluated nonsevere pneumonia. Methods. We conducted a retrospective multicenter study using Epic Cosmos data from 2016-2025. Hospitalized patients treated empirically by 24 hours were compared by continuation during hours 24-48; outpatients were compared by prescription at emergency-department discharge. Analyses were stratified by guideline-defined comorbidity and used propensity-score overlap weighting with source-cluster bootstrap confidence intervals. Exploratory analyses assessed respiratory virus, antiviral treatment, antibacterial class, and outpatient timing. Measurements and Main Results. The cohort included 376,320 adults: 275,604 inpatients and 100,716 outpatients. Inpatients who continued treatment had higher 30-day adverse-event risk without guideline comorbidity (adjusted risk difference, 1.70 percentage points; 95% confidence interval, 0.80-2.39) and with guideline comorbidity (2.56; 1.88-3.14), and longer post-landmark stay (adjusted mean ratios, 1.14 and 1.08). Exploratory class-specific analyses showed the largest adverse-event and mortality associations with broad therapy targeting resistant staphylococci or Pseudomonas; macrolide-containing and other atypical coverage showed no consistent adverse signal. Outpatient prescribing was associated with lower risks, but care-transition and residual confounding remained. Conclusions. Continued inpatient therapy after the empiric period showed no evidence of benefit and was associated with worse observed outcomes. Outpatient associations favored prescribing but remained vulnerable to care-transition and residual confounding.