Clinical Microbiology and Infection

The emergence of vaccine covered serotypes causing invasive pneumococcal disease (IPD) is a serious concern worldwide. We investigated the unexpected rise of serotype 4 causing IPD primarily in non-vaccinated young adults after the COVID-19 pandemic that further spread to adults [≥] 65 years in recent years. For this purpose, we conducted a retrospective study of serotype 4 IPD cases (n=827) reported in Spain between 2009 and 2024. Whole-genome sequencing was performed to assess clonal lineages and phylogenetic relationships. Clinical and epidemiological data were compared between serotype 4 and all other serotypes causing IPD. Epidemiological and genomic analysis confirmed that the rise started as an abrupt cluster of IPD cases in Seville (Andalusia) in the year 2022 due to the ST15063 within GPSC12 lineage. This outbreak initially caused pneumonia episodes that required hospitalization in young individuals associated with high rates of tobacco smoking, alcohol, and inhaled drugs such as cannabis and cocaine, followed by a general distribution pattern throughout the country in the following years, affecting the elderly population. Experimental studies to evaluate potential underlying mechanisms confirmed that ST15063 serotype 4 strains displayed enhanced infection rates of human lung cells that significantly increased in the presence of cigarette smoke exposure and by influenza H3N2 virus coinfection, but not with H1N1. These findings highlight the need for targeted vaccination strategies not only against pneumococcus but also against respiratory viruses such as influenza, RSV and COVID-19 and demonstrate the importance of molecular surveillance to establish effective interventions in high-risk populations.

BackgroundThe strength and transparency of clinical trial evidence supporting drug approvals has become increasingly scrutinized, particularly considering the increased use of regulatory flexibility and expedited pathways. While U.S. Food and Drug Administration (FDA) standards have been extensively analyzed, evidence standards at the European Medicines Agency (EMA) remain less well-characterized. Thus, this study aims to systematically assess the design, quality, and outcomes of pivotal efficacy trials supporting EMA drug approvals between 2020 and 2023. MethodsWe conducted a cross-sectional analysis of new medicines and biosimilars receiving positive opinions from the EMAs Committee for Medicinal Products for Human Use (CHMP) and subsequent approval by the European Commission between January 2020 and December 2023. Data were extracted from European Public Assessment Reports (EPARs) and EMA medicine databases. Key variables included trial design features, primary endpoint type and achievement status, and justification for approval in cases of failed efficacy endpoints. ResultsBetween 2020 and 2023, 232 drugs were approved by the EMA for 281 indications. Of these, 205 (88.4%) were new active substances and 65 (28.0%) were granted orphan designation. Forty-six products (19.8%) were approved via a special regulatory program, most commonly Conditional Approval (26 products; 11.2%). Cancer was the leading therapeutic area, accounting for 61 approvals (26.3%). Approvals were supported by 393 pivotal clinical trials. Of these, 327 (83.2%) were randomized controlled trials (RCTs) and 218 (66.6% of RCTs) had a superiority design. A total of 232/393 trials (59.0%) relied on surrogate endpoints. Overall, 22 approvals (9.5%) were supported by at least one pivotal trial in which at least one primary endpoint was not met; in seven of these cases (31.8%), the failed trial was the sole pivotal trial. The most common rationale for approval despite null primary results was reliance on the totality of evidence, secondary endpoints, or clinical judgment (9 products; 40.9%). ConclusionsOur findings reveal substantial variability in the design and evidentiary strength of pivotal trials supporting EMA approvals between 2020 and 2023. While the majority of studies were RCTs, reliance on surrogate endpoints was common. That 10% of approvals were based on pivotal trials with null primary endpoints highlights the nuanced role of regulatory judgment in therapeutic evaluation. These findings prompt reflection on evolving evidence standards in drug regulation and underscore the need for transparency and consistent justifications.

IntroductionThe Japanese Ministry of Health, Labour, and Welfare proposed increased copayments for over-the-counter (OTC)-like drugs, with possible special consideration for certain chronic diseases, although the specific diseases to be included were not clarified as of January 2026. The costs attributable to OTC-like drugs indicated for chronic diseases in adults remain unclear. MethodsUsing the DeSC database (individual-level claims data) in fiscal year 2023, we estimated the average per-person annual costs of the study OTC-like drugs indicated for adults with representative chronic diseases. The estimates were stratified by sex and age. We also computed the national estimates of the numbers of adults with representative chronic diseases who would need OTC-like drugs and the costs attributable to these drugs by applying stratum-specific estimates from the DeSC database to national population counts and aggregated claims data from the National Database of Health Insurance Claims Open Data. The study OTC-like drugs included oral acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical anti-inflammatory patches, oral second-generation antihistamines, and heparinoid-containing topical preparations. ResultsThe average per-person annual costs were several hundred yen for acetaminophen and several thousand yen for the other drug categories, with marked variation by drug category, chronic disease, age, and sex. In the national estimates, the proportion of OTC-like drug users with representative chronic diseases was <10% in every disease-age-sex stratum; nevertheless, the maximum stratum-specific shares of total OTC-like drug costs attributable to these groups were high (up to 50-60% for osteoarthritis for acetaminophen/NSAIDs/patches and up to [~]60% for atopic dermatitis/asteatosis for heparinoids). ConclusionsThe average per-person annual costs for OTC-like drugs varied substantially across drug categories and patient subgroups. Indicated chronic diseases in adults may account for substantial OTC-like drug costs within some strata, despite representing a small fraction of users.

We genotyped 1189 multidrug-resistant Mycobacterium tuberculosis isolates identified during 2013-2022 in Argentina, through a mixed strategy using PCR-based methods and whole-genome sequencing. Epidemiological, geographic distribution and microbiological data were integrated. Most cases belonged to a cluster (75.7%). The proportion of orphan and clustered cases varied across regions. The Euro-American lineage4 was virtually predominant. The most important clusters, M, Ra, Rb and Callao2 strains, comprised 45.9% of the newly diagnosed cases, and their relative importance varied over time. A preliminary genomic analysis showed that several local transmission chains due to the Callao2 strain, imported from Peru, were active, including a superspreading event that occurred circa 2020. A good performance of the current second-line regimes can be expected for most of the cases. Heightening suspicion of drug-resistance and enhancing timely and active surveillance in specific risk groups could contribute to the tuberculosis management in Argentina, tackling transmission and resistance amplification. BiosketchBiochemist Federico Lorenzo is a professional of the Servicio de Micobacterias, Departamento de Bacteriologia, INEI, ANLIS "C. G. Malbran" and is specialized in the microbiological diagnosis of mycobacterial diseases using next-generation sequencing technologies. His research interests are drug-resistant tuberculosis, non-tuberculous mycobacteria and bioinformatic analysis applied to diagnostics. One-sentence summaryWe evaluated the genotypes associated with multidrug-resistant tuberculosis in Argentina, 2013-2022.

Background: Since September 2024, France has implemented a national reform allowing prescription-free access (PFA) to sexually transmitted infection (STI) screening in medical biological laboratories (MBLs). This study aims to characterize the populations undergoing STI testing according to their access modality and evaluate the probability of test positivity in relation to testing pathway, sex, and age groups. Methods: We conducted a cross-sectional analysis of all individuals screened for Chlamydia trachomatis, Gonorrhoea, human immunodeficiency virus (HIV), hepatitis B virus (HBV), and syphilis by treponemal-specific immunoassay (TSI) in Cerballiance MBLs between Mars 2025 and February 2026. Multivariable logistic regression models stratified by sex and adjusted for age and region assessed associations between screening modality and STI positivity. Results: Among 1,008,737 individuals included, 27.8% were under PFA and 72.2 under prescription-based access (PBA). PFA users were more frequently male (47.4% vs. 36.3%, p<0.001) and aged 20-39 years (34.0%, p<0.001). Overall positivity rates differed by modality: PFA was associated with higher detection of Chlamydia (4.6% vs. 3.6%). PBA group showed more positive cases of syphilis (3.4% vs. 1.2%), HBV (1.3% vs. 0.4%), and HIV infections (0.3% vs. 0.2%, all p<0.001). Co-infection and gonorrhoea proportions did not significantly differ between modalities. Conclusions: PFA substantially increased STI screening uptake, particularly among young adults and men, and enhanced detection of bacterial STIs. PBA remains essential for diagnosing viral and chronic infections. These findings highlight the complementary roles of both access strategies and support PFA screening as an effective public health intervention to broaden STI detection and reduce transmission.

BackgroundHigh-risk human papillomavirus (HR-HPV) infection is the necessary cause of cervical cancer, a leading cause of cancer mortality among women in sub-Saharan Africa. In Cameroon, there is a gap in synthetized evidence on HR-HPV epidemiology, limiting data-driven prevention strategies. This study provides the first comprehensive national synthesis of HR-HPV prevalence, genotype distribution, and HIV co-infection among HPV-infected individuals. MethodsA systematic review and meta-analysis were conducted following PRISMA guidelines and registered in PROSPERO (CRD420261282094). We systematically searched PubMed, Scopus, Web of Science, Embase, Cochrane Library, AJOL and local online publishers. Studies reporting the prevalence of HR-HPV among sexually active individuals were included. Pooled prevalence estimates were calculated using random-effects meta-analysis. Heterogeneity was assessed with I{superscript 2} statistics and explored through subgroup analyses. The methodological quality of included studies was evaluated using the Joanna Briggs Institute (JBI) critical appraisal tools. ResultsA total of 33 studies including 18,798 participants were included in this analysis. The overall pooled prevalence of HR-HPV was 28.95% (95% CI: 19.74-40.30; 33 studies; n = 18,798; I2 = 98.7%), with a notable decline from 53.34% before 2014 to 21.43% in 2021-2023. Prevalence varied substantially across populations, being highest among women with precancerous or cancerous lesions (90.69%; 95% CI: 78.48-96.30) and female sex workers (62.10%; 95% CI: 58.08-66.00) compared to women from the general population (21.09%; 95% CI: 15.16-28.55). Among HPV-positive women, HIV co-infection prevalence was 26.17% (95% CI: 13.48-44.65, 19 studies; n = 3,589; I2 = 97.9%), with higher rates in hospital-based studies (34.57%) compared to community-based studies (9.18%). Predominant HR-HPV genotypes included HPV16 (28.7%), HPV52 (23.6%), HPV6 6 (22.9%), HPV33 (22.8%), and HPV18 (20.2%). The pooled prevalence of abnormal cervical lesions among HPV-positive women was 35.15% (95% CI: 20.21-53.70; 12 studies; n = 2,186; I2 = 95.2%), comprising low-grade lesions (34.4%) and high-grade lesions (19.1%). ConclusionsHigh-risk human papillomavirus infection remains highly prevalent in Cameroon despite encouraging temporal declines. The substantial burden of HIV co-infection and circulation of multiple oncogenic genotypes underscore the need for integrated HPV-HIV prevention strategies, expanded screening, and consideration of broader-coverage vaccines to accelerate progress toward cervical cancer elimination targets.

ObjectivesTo quantify how urine sample type and polymicrobial context impact antimicrobial resistance (AMR) in urinary tract infections (UTIs), using routine diagnostics at scale. MethodsIn this retrospective, single-centre study, we analysed 188,687 urine cultures from the Institute of Medical Microbiology, University of Zurich, Switzerland (January 2015 to May 2023). We compared midstream urine (MU), indwelling catheter (IDC), and intermittent catheter (IMC) samples. Samples were classified as negative, bacteriuria, or UTI, by meeting a microbiological UTI threshold ([&ge;]105 CFU/mL). We compared sample types using covariate-adjusted regression and constrained ordination for community composition. In bimicrobial cultures, we assessed co-occurrence using adjusted pairwise odds ratios and degree-preserving permutation null models, supported by partner-choice analyses. AMR was modelled as acquired resistance (AR) and total resistance (TR: acquired + intrinsic) probabilities, with predictor contributions quantified using mutual information. ResultsAmong 186,819 MU, IMC, IDC samples, 56,867 met the UTI threshold. Catheter-associated UTIs (IDC and IMC) were ~60% more likely to be polymicrobial than MU samples. Community composition differed by sample type (p<0{middle dot}001). In IDC, Escherichia coli was less prevalent than in MU, but device-associated pathogens like Pseudomonas aeruginosa and Candida albicans were enriched. Most species-pairs showed no increased co-occurrence after adjusting for covariates, but a subset showed reproducible enrichment across methods (e.g., C. albicans-C. glabrata). Organism identity was the dominant determinant of AMR, with the highest mutual information across AR and TR. AR was higher in IDC for common uropathogens (e.g., E. coli). Co-isolation with hospital-associated partners (e.g., Enterococcus faecium) was associated with further AR increase. From 2015 to 2023, AR increased from ~48% to ~60%, with rising {beta}-lactam (+{beta}-lactamase inhibitor) resistance and declining fluoroquinolone resistance in Enterobacterales. ConclusionsSample type and co-isolated partners provide clinically actionable information beyond pathogen identity and could support more context-aware reporting and empiric prescribing.

Objectives: To assess the availability of key clinical trial registration data and compliance with legal reporting requirements for all Phase 2-4 drug trials registered on the new European Clinical Trial Information System (CTIS) registry. This study is the first ever assessment of data quality and legal compliance with reporting requirements on CTIS. Design: Cross-sectional observational study of CTIS registry data combined with manual review of results documents. Setting: Cohort of all 7,547 Phase II-IV clinical trials registered on CTIS as of November 2025. Main outcome measures: Number and proportion of missing data points in CTIS registration data. Proportion of completed clinical trials that are compliant with regulatory reporting requirements. Results: Trial registration data quality was high overall with more than 99% of expected data present. Of 234 clinical trials legally required to report results, fewer than half (49.6%) fully reported results within the required timeframe, 20 trials (8.5%) fully reported results late, and 98 trials (41.9%) failed to fully report results. Legal compliance was similar for adult trials (79/158) and paediatric trials (37/76). Conclusions: Sponsor compliance with legal reporting requirements is weak. Current efforts by European regulators to monitor and enforce compliance appear to be insufficient. New results reporting functions currently being set up by trial registries worldwide will require quality assurance processes. Trial registration: Study protocol prospectively registered on OSF: https://osf.io/sn4j2/overview

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.

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.

BackgroundNumerous studies reporting utility of microbial blood biomarkers for diagnosis and treatment monitoring of M. tuberculosis (Mtb) infection and tuberculosis disease have been conducted, but up-to-date systematic reviews and meta-analyses of these data are lacking. We aimed to evaluate diagnostic accuracy of microbial blood biomarkers for detection of tuberculosis disease and to characterise their responses to antimicrobial therapy. MethodsFor this aggregate data meta-analysis, we searched MEDLINE, EMBASE and Scopus from 1st January, 1990, to 22 October, 2025, using terms for "tuberculosis", "microbial biomarker", and "human blood" to identify studies in which participants underwent blood sampling for detection of cell-free Mtb DNA, cell-associated Mtb DNA, protein/peptide Mtb antigens and lipid/glycolipid Mtb antigens before {+/-} after initiation of antimicrobial therapy. For bivariate analyses we used hierarchical summary receiver operating characteristic (HSROC) models to calculate areas under HSROC curves (AUC) for each analyte class to evaluate diagnostic accuracy for tuberculosis disease. For longitudinal analyses, we calculated risk differences to evaluate changes in proportions of biomarker-positive individuals after vs. before initiation of antimicrobial therapy, and pooled them using random-effects meta-analysis. Findings137 eligible articles were identified in the search, of which 109 vs. 13 contributed data to bivariate vs. longitudinal analyses, respectively. For cell-free Mtb DNA targets, AUC was 0.87 (95% CI 0.84 to 0.89), with sensitivity 61.5% (51.0 to 71.0) and specificity 93.0% (88.1 to 96.1); 4,878 samples from 34 unique study/setting/biomarker combinations (investigations). For cell-associated Mtb DNA targets, AUC was 0.93 (0.90 to 0.95), with sensitivity 43.9% (29.4 to 59.4) and specificity 97.1% (94.5 to 98.5); 3,589 samples, 32 investigations. For protein/peptide targets, AUC was 0.94 (0.92 to 0.96), with sensitivity 78.9% (73.2 to 83.6) and specificity 92.9% (90.7 to 94.5%); 10,260 samples, 61 investigations. For lipid/glycolipid targets, AUC was 0.96 (0.94 to 0.97), with sensitivity 68.6% (54.1 to 80.3) and specificity 97.0% (94.0 to 98.5); 3,287 samples, 22 investigations. Pooled risk differences for proportions of individuals biomarker-positive after vs. before initiation of antimicrobial therapy were -0.44 (-0.89 to 0.01; 68 samples, 5 investigations) for cell-free Mtb DNA; -0.46 (-0.88 to -0.03; 89 samples, 5 investigations) for cell-associated Mtb DNA, and -0.24 (-0.75 to 0.28; 160 samples, 4 investigations) for protein/peptide antigens. No studies investigating responses of lipid/glycolipid antigens to antimicrobial therapy were identified. Heterogeneity was moderate (I2 25-50%) for the majority of studies. 98/109 and 11/13 studies contributing data to bivariate vs. longitudinal analyses, respectively, were assessed as being at high risk of bias. InterpretationMolecular and biochemical microbial blood biomarkers exhibit similar accuracy for detection of tuberculosis disease, with specificity consistently exceeding sensitivity. Cell-associated Mtb DNA biomarkers exhibited a statistically significant response to antimicrobial therapy, with similar trends observed for cell-free Mtb DNA and protein/peptide antigens. These findings should be interpreted cautiously in the light of high risk of bias for many of the primary studies contributing data. Higher quality studies are needed to evaluate this emerging class of tuberculosis biomarkers. FundingBarts Charity, The Medical College of Saint Bartholomews Hospital Trust, Wellcome HARP Doctoral Fellowship Scheme. RESEARCH IN CONTEXT Evidence before this studyThe World Health Organisation (WHO) has identified high-priority biomarker needs for screening, diagnosis, evaluating likelihood of disease progression and treatment monitoring for tuberculosis. Numerous studies reporting utility of microbial blood biomarkers for diagnosis and treatment monitoring of M. tuberculosis (Mtb) infection and tuberculosis disease have been conducted, but up-to-date systematic reviews and meta-analyses of these data are lacking. We performed a systematic search of MEDLINE, EMBASE and Scopus from 1st January, 1990, to 22 October, 2025, using terms for "tuberculosis", "microbial biomarker", and "human blood" to identify studies in which participants underwent blood sampling for detection of cell-free Mtb DNA, cell-associated Mtb DNA, protein/peptide Mtb antigens and lipid/glycolipid Mtb antigens before {+/-} after initiation of antimicrobial therapy. Multiple studies have investigated utility of microbial blood biomarkers for detection of tuberculosis disease and monitoring responses to antimicrobial therapy, but only three relevant systematic reviews have been conducted to date, of which two (2007, 2021) report on detection of cell-free Mtb DNA, and one (2011) reports on antigen detection tests. Numerous primary studies have been published since these meta-analyses were conducted, but up-to-date syntheses incorporating the latest data for all classes of microbial blood biomarker for tuberculosis are lacking. Added value of this studyTo our knowledge, this study is the most comprehensive systematic review and meta-analysis of data from studies of microbial blood biomarkers of Mtb infection and tuberculosis disease conducted to date. It is also the first meta-analysis to synthesise data from studies investigating detection of cell-associated Mtb DNA in blood. Bivariate analysis of data from 109 studies revealed AUC values of 0.87 to 0.96 for the four microbial biomarker classes investigated, with sensitivity vs. specificity ranging from 43.9% to 80.2% vs. 87.9% to 97.1%, respectively. Cell-associated Mtb DNA biomarkers exhibited a statistically significant response to antimicrobial therapy, with similar trends observed for cell-free Mtb DNA and protein/peptide antigens. However, most primary studies were assessed as being at high risk of bias. Implications of all the available evidenceMolecular and biochemical microbial blood biomarkers exhibit similar accuracy for detection of tuberculosis disease, with specificity consistently exceeding sensitivity. Cell-associated Mtb DNA biomarkers exhibited a statistically significant response to antimicrobial therapy, with similar trends observed for cell-free Mtb DNA and protein/peptide antigens. These findings should be interpreted cautiously in the light of high risk of bias for many of the primary studies contributing data. Higher quality studies are needed to evaluate this emerging class of tuberculosis biomarkers.

Human papillomavirus (HPV) testing is the primary method for cervical cancer screening, and a negative HPV test is associated with a very low subsequent risk of invasive cancer. Nevertheless, a small number of cervical cancers are diagnosed following an HPV-negative testing result, posing challenges within HPV-based screening pathways. Using nationwide Swedish registry data of HPV testing, we identified women diagnosed with invasive cervical cancer between 2019 and 2024 and reconstructed HPV testing histories from the National Cervical Screening Registry (NKCx). The most recent HPV test prior to diagnosis was defined as the index test, and longitudinal HPV testing trajectories were classified among women with an HPV-negative index test. Of 3,000 women diagnosed with invasive cancer, 243 (8.1%) had an HPV-negative index test. These women were older at diagnosis and more frequently diagnosed at advanced stages compared with women with an HPV-positive index test. Most HPV-negative index tests (66.3%) were performed in the peri-diagnostic period (+/- 30 days). Among women with an HPV-negative index test, 52.7% (128/243) had no prior HPV testing recorded, while the remainder had consistently HPV-negative histories (33.3%, 83/243) or evidence of prior HPV positivity before the index negative test (14%, 32/243). Possible recurrent HPV positivity following an intervening negative test was rare (0.4%, 1/243). HPV-negative screening results preceding invasive cancer reflect heterogeneous screening histories and cannot be explained solely by test failure. Findings highlighting the importance of reaching women earlier in screening programs and show that fluctuating HPV detectability is rare.

Objectives: To identifiy risk factors for antimicrobial resistance (AMR) in seven pathogen-antimicrobial combinations in patients with cancer and cancer survivors. Methods: Using data from patients with recent or past cancer diagnostic codes in Oxfordshire, UK, we examined associations between 22 potential risk-factors and AMR in blood culture isolates, collected between 1-April-2015 and 31-March-2025. Results: Among 5,975 bacteraemias in 4,365 adults, we analysed 3,141 (52.6%) due to Enterobacterales and 620 (10.4%) due to Enterococcus faecalis/faecium in 2,752 patients. Fourteen risk-factors for antimicrobial-resistant bacteraemia were identified, varying across pathogen-antimicrobial combinations. Compared with no previous antimicrobial susceptibility test result, prior resistance to the same antibiotic in any culture in the last year was strongly associated with AMR across all pathogen-antimicrobial combinations (all p<=0.001). Prior antibiotic exposure and younger age were also positively associated with AMR in four and five combinations, respectively. Cancer type showed modest effects; lymphoid/haematopoietic malignancies were associated with higher odds (vs colorectal cancer) of trimethoprim-sulfamethoxazole-resistant Enterobacterales (aOR=2.07 95%CI 1.40-3.06) and vancomycin-resistant Enterococcus bacteraemia (aOR=6.68, 1.21-36.91). Conclusions: Previous resistance was the greatest risk factor for bacteraemia with AMR in cancer patients and survivors, with prior antibiotic exposure and age also contributing. Lymphoid/haematopoietic malignancies increased risk of resistance to specific antimicrobials. Keywords: antimicrobial resistance, bacteraemia, cancer, risk factors

ImportanceRecent reports have highlighted an intense influenza activity related to the circulation of the influenza A(H3N2) subclade k variant. There is no data available on the impact of the emergence of H3N2 subclade k on the severity of the 2025-2026 epidemic or on the clinical phenotype of patients requiring admission to the intensive care unit (ICU). ObjectiveTo compare the clinical presentation, hospital mortality and virological characteristics of patients with laboratory-confirmed influenza infection included in French intensive care units during the 2025-2026 epidemic season with those of patients admitted during the 2024-2025 season. We also aimed at measuring the impact of the A(H3N2) subtype on hospital mortality during the 2025-2026 season. DesignProspective, multicenter, observational SEVARVIR cohort study including patients admitted during the 2024-2025 and 2025-2025 influenza seasons. SettingForty-two French ICUs ParticipantsAdult patients with laboratory-confirmed influenza infection Interventionsnone Main Outcomes and MeasuresThe primary outcome measure was in-hospital mortality. ResultsPatients admitted in intensive care units for influenza in 2024-2025 (n=360) and 2025-2026 (n=325) were included in the French nationwide prospective multicentre SEVARVIR study. There was no significant difference in day-28 mortality between the seasons (12.7%, n=45/355 vs 16.5% n=28/170; p=0.28). In the 2025-26 season, 49% had the A(H1N1) subtype and 51% the A(H3N2) subtype (k subclade: 77%). The univariable Cox analysis revealed that patients infected with A(H3N2) viruses were at greater risk of death over time. Multivariable Cox analysis revealed that during the 2025-2026 season, age (adjusted hazard ratio, aHR=1.05 [1.00;1.11]; p=0.046) and the clinical frailty scale (aHR=1.82 [1.26;2.72]; p=0.001) were associated with an increased risk of death. The A(H3N2) subtype was not associated with an increased risk of death (aHR=1.13 [0.32;4.51]; p=0.85). Phylogenetic analyses from our ICU cohort together with 300 contextual sequences from community-acquired influenza cases collected during the same period showed no clustering according to severity. Conclusions and RelevanceThis French national prospective observational study, found that the emergence of the influenza A(H3N2) subclade K was associated with an increased risk of death in univariable but not multivariable analysis, adjusting for host-related factors. Trial RegistrationNCT051625 Key PointsQuestion: What impact did the 2025-26 influenza epidemic and the A(H3N2) variant have on the mortality of patients admitted to intensive care units? Findings: In this prospective, nationwide cohort study of 685 patients admitted to intensive care units with severe influenza during the 2024-25 or 2025-26 seasons, no difference in hospital mortality was observed between the two seasons. Patients infected with the A(H3N2) virus, 77% of which corresponded to clade k, were at higher risk of death in univariable but not in multivariable analysis after adjusting for age and clinical frailty scale. Meaning: Patients in intensive care units with severe A(H3N2) infection during the 2025/2026 season were not at higher risk of death after adjusting for confounding variables.

Introduction Improved diagnostics are needed for people at risk of tuberculosis, especially adolescents. Tongue swab (TS) molecular testing has emerged as a promising strategy for tuberculosis diagnosis. We evaluated diagnostic accuracy and acceptability of Xpert MTB/RIF Ultra (Xpert) using TS samples for tuberculosis detection among adolescents. Methods We conducted a cross-sectional diagnostic accuracy study with consecutive recruitment in Vietnam. Adolescents aged 10-19 who were recommended to undergo investigation for tuberculosis and had not received tuberculosis treatment in the past years were eligible. Participants provided TS and sputum samples and completed a structured survey regarding sampling experiences. TS was tested on Xpert, with sputum tested on Xpert and liquid culture. We utilised a composite reference standard of a positive result on sputum Xpert or sputum culture to define disease status. Sensitivity, specificity, and diagnostic yield were calculated for TS Xpert. Results From July to December 2025, we enrolled 225 adolescents from Can Tho and An Giang provinces in southern Vietnam. Fewer than half (96/225, 43%) the participants exhibited a tuberculosis -like symptom, and the majority (157/225, 70%) were close contacts of a person recently diagnosed with tuberculosis. TS were collected from all adolescents, while 116 (52%) could provide mucopurulent sputum. Tuberculosis prevalence was relatively low (12/225, 5.3%). TS Xpert sensitivity (90% CI) and specificity (90% CI) were 58.3% (35.6, 78.0) and 99.5% (97.9, 99.9), respectively. Diagnostic yield among all diagnosed was 58.3% (7/12). TS sampling was highly acceptable to adolescents; the short time and simplicity of collecting TS were considered favourably. Conclusions The sensitivity and diagnostic yield of TS Xpert was relatively low among adolescents recommended for tuberculosis investigation, which includes asymptomatic individuals who may not provide high quality sputum. Specificity was excellent, and everyone could provide a TS. TS high acceptability indicates it remains a promising sample for diagnostic algorithms.

The objective of this study was to re-analyse the molecular phylogeny and/or the morphology of all species, which have been attributed to the so-far mono-generic fungal family Ambisporaceae. The genus Ambispora has been well-known for its spore bi-morphy described even from single spore clusters. Triple-walled spores are differentiated on sporiferous saccules, while mono-walled spores are formed on simple subtending hyphae. New phylogenetic analyses reveal dissimilarities of [&ge;]10% in partial nrDNA gene of three different stable phylogenetic clades and thus suggest the division of Ambispora into three genera, which simultaneously request for advanced morphological separations. These advances are primarily based on the more diverse spore wall composition of the ambisporoid-acaulosporoid morph rather than on the rather simple-glomoid morph. While all known species of the triple-walled morph have an evanescent to semi-permanent outer spore wall, i) Am. fennica, Am. brasiliensis, Am. gerdemannii and Am. nicolsonii have a smooth, permanent central spore wall (Am. fennica clade, A), ii) the central wall of Am. appendicula, Am. callosa, Am. leptoticha and Am. jimgerdemannii is alveolate (Am. appendicula clade, B), and iii) the central wall of Am. granatensis is smooth, but easily degraded, thus rather short-lived and not permanent but evanescent (Am. granatensis clade, C). In conclusion, species of the Am. fennica clade represent the genus Ambispora, while species of the Am. appendicula clade represent the new genus Appendiculaspora, and the mono-specific Am. granatensis clade represents the new genus Ephemerapareta. Species of an additional morph, with triple-walled spores, but apparently formed on subtending hyphae, and having a diagnostic reticulate, football-like middle wall, are here separated from the revised genus Ambispora based solely on morphological analyses, since molecular identification analyses so far failed and remained merely unknown. This later morph and genus is based on the type species Pelotaspora reticulata comb. nov, and on P. austrolatina sp. nov. Concomitant molecular phylogenetic and morphological analyses are needed to attribute not only Pelotaspora spp., but also those species, for which hitherto only the ambisporoid-glomoid morph has been observed correctly within the family Ambisporaceae. Without molecular analyses, such species with glomoid but unknown ambisporoid-acaulosporoid morph have to be retained within Ambispora.

BackgroundPeripheral neuropathy frequently leads to linezolid dose reductions or interruptions during multidrug- or rifampicin-resistant tuberculosis treatment. The effect of these modifications to linezolid on treatment success is uncertain. MethodsWe conducted a target trial emulation using the endTB Observational Study among individuals who developed mild or moderate peripheral neuropathy while receiving linezolid 600 mg daily within 6 months of initiating an individualized regimen. We examined three linezolid management strategies: immediate change (suspension or dose reduction) during Weeks 1-7, deferred change during Weeks 8-26, and no change (i.e., continuing linezolid 600 mg daily) during Weeks 1-26. We used a clone-censor-weight approach to estimate the observational analog of the per-protocol effect on treatment success. ResultsAmong 303 eligible participants from 12 countries, peripheral neuropathy occurred a median (interquartile range) of 11 (4-18) weeks after treatment initiation. Weighted, standardized probabilities of treatment success were 85.8% (95% CI: 72.7%, 93.9%) for immediate change, 78.8% (95% CI: 66.1%, 87.1%) for deferred change, and 85.2% (95% CI: 80.5%, 89.1%) for no change. Compared with no change, treatment success ratios were 1.01 for immediate change (95% CI: 0.86, 1.11) and 0.93 for deferred change (95% CI: 0.78, 1.01) strategies. ConclusionsWe did not find evidence of a substantial negative impact of immediate modification to linezolid among people who developed mild or moderate peripheral neuropathy in the first six months of an individualized regimen. Our results support the clinical practice of cautiously adjusting linezolid when needed to manage non-severe peripheral neuropathy. Key pointsIn this target trial emulation, we found that immediate modifications to linezolid (dose reduction or suspension) in response to mild or moderate peripheral neuropathy during the first six months of MDR/RR-TB treatment did not substantially compromise MDR/RR-TB treatment success.

Background: Correctional facilities are vital venues for expanding testing and treatment for hepatitis C virus (HCV) infections, essential components of national hepatitis C elimination plans. Objective: This study characterizes HCV testing and treatment outcomes among individuals entering incarceration into California state prisons, overall, by year, and by key individual-level characteristics. Methods: We analyzed individual-level electronic health record data from all adults entering California prisons ('entrants') between July 1, 2016 and June 30, 2023. We quantified the percentages of entrants receiving an HCV antibody test within four weeks of entry, the percentage antibody positive among tested, the percentage RNA positive among antibody positive, and the percentage initiating direct acting antiviral (DAA) treatment within one year among RNA positive. Results: Of entrants, 133,639 (76%) were tested for HCV antibody, 25,455 (19% of tested) were ever HCV-infected, and 16,738 (66% of ever infected) were currently infected. Among individuals currently infected, 7,479 (45%) initiated DAA treatment within one year. Individuals with identified SUD had 3.2 times higher antibody positivity and 1.3 times higher proportions initiating DAA, compared to individuals not having an identified SUD. Discussion: We show that HCV testing and treatment in California prisons, a central component of national hepatitis C elimination efforts, supported effective and equitable increases in access to hepatitis C treatment, particularly for those with SUD.

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide, with Escherichia coli being the predominant uropathogen. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains and their association with fluoroquinolone resistance pose a significant challenge to empirical therapy, particularly in community settings. The aim of this study was to determine the epidemiology and predictive factors associated with ESBL-producing E. coli and its concomitant fluoroquinolone resistance in community-acquired clinical isolates. A retrospective cross-sectional study was conducted analyzing 244 clinical E. coli isolates. Demographic and microbiological data were collected, including age, sex, sample type, and antibiotic susceptibility. Associations between variables and ESBL production were assessed using Pearsons chi-squared test, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of the isolates, 165 (68%) were ESBL-producing. A significant association was observed between age group and ESBL production (p < 0.001), with the highest frequency in the 20-39 age group. Most ESBL-positive isolates were obtained from women (73%), although odds ratio (OR) analysis suggested a non-significant trend toward a higher probability in men (OR = 1.29; 95% CI: 0.72-2.31). High rates of fluoroquinolone resistance were identified among the ESBL-producing isolates, with 30% resistance to levofloxacin and 35% to ciprofloxacin (p < 0.001). Urine samples showed the highest concentration of ESBL-positive isolates, with a significant association between sample type and resistance (p < 0.001). The high prevalence of ESBL-producing E. coli and its concomitant resistance to fluoroquinolones highlight a critical challenge for the empirical treatment of urinary tract infections in Mexico, underscoring the need to strengthen antimicrobial use management and local surveillance strategies.

BackgroundTuberculosis (TB) remains a leading cause of infectious disease mortality worldwide, and treatment failure contributes to ongoing transmission, drug resistance, and poor clinical outcomes. Artificial intelligence and machine learning approaches have attracted growing interest for predicting tuberculosis treatment outcomes, but the literature is heterogeneous and lacks a comprehensive synthesis. MethodsWe conducted a systematic review and meta-analysis of studies that developed or validated machine learning models to predict TB treatment failure. We searched PubMed/MEDLINE and Embase from January 2000 to October 2025. Studies were eligible if they developed, validated, or implemented an artificial intelligence or machine learning model for the prediction of TB treatment failure or a closely related poor outcome in patients receiving anti-TB treatment. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. Random-effects meta-analysis was performed to pool area under the curve values, with subgroup analyses and meta-regression to explore heterogeneity. ResultsThirty-four studies were included in the systematic review, of which 19 reported area under the curve values suitable for meta-analysis (total participants, 100,790). Studies were published between 2014 and 2025, with 91% published from 2019 onward. Tree-based methods were the most common algorithm family (52.9%), and multimodal models integrating three or more data types were used in 41.2% of studies. The pooled area under the curve was 0.836 (95% confidence interval 0.799-0.868), with substantial heterogeneity (I{superscript 2} = 97.9%). In subgroup analyses, studies including HIV-positive participants showed lower discrimination (pooled area under the curve 0.748) compared to those excluding them (0.924). Only eight studies (23.5%) performed external validation, and only one study (2.9%) was rated as low risk of bias overall, primarily due to methodological concerns in the analysis domain. Eggers test suggested publication bias (p = 0.024). Major evidence gaps included underrepresentation of high-burden countries, HIV-affected populations, social determinants, pediatric TB, and extrapulmonary disease. ConclusionsMachine learning models for predicting TB treatment failure show promising discrimination but are not yet ready for routine clinical implementation. Performance varies substantially across populations and settings, and methodological limitations, including inadequate validation, poor calibration assessment, and high risk of bias, limit confidence in current estimates. Future research should prioritize rigorous external validation, calibration assessment, and development in underrepresented populations, particularly HIV-affected and high-burden settings. Author SummaryTB kills over a million people annually. While curable, treatment failure remains common and drives ongoing transmission and drug resistance. Researchers increasingly use artificial intelligence and machine learning to predict which patients will fail treatment, but it is unclear if these models are ready for clinical use. We reviewed 34 studies including nearly 1.1 million participants from 22 countries. On average, models correctly distinguished patients who would fail treatment from those who would not 84% of the time, a performance generally considered good. However, this average hid enormous variation. Models developed in populations including HIV-positive people performed substantially worse, suggesting prediction is harder with HIV co-infection. Worryingly, only one study used high-quality methods; 97% had serious flaws in handling missing data, checking calibration, or testing in new populations. Only eight studies validated their models in different settings. To conclude, we found that machine learning is promising in predicting TB treatment failure, but it is not ready for clinical use. Researchers should prioritize validation in high-burden settings, include social determinants, and improve methodological rigor before these tools can help patients.