Infectious Diseases and Therapy最新文献

{"title":"Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.","authors":"Klaus-Friedrich Bodmann, Alessandra Mularoni, Giovanna Russelli, Valentina Galfo, Giusy Tiseo, Francesco Alessandri, Giancarlo Ceccarelli, Eleni Mouloudi, Stavrina Avgeropoulou, Loredana Sarmati, Laura Campogiani, Ivan Gentile, Kai Zacharowski, Stefan Kluge, Dominik Jarczak, Christina Iasonidou, Stefan Hagel, Alessandro Capone, Alessandra Bandera, Daniele R Giacobbe, Annalisa Saracino, Pavlos Myrianthefs, Markos Marangos, Michael Zoller, Jan T Kielstein, Carlo Tascini, Antonio Cascio, Abhijit M Bal, Francesca Ferretti, Valerio Del Bono, Despina Hatzilia, Stelios F Assimakopoulos, Evangelos J Giamarellos-Bourboulis, Marco Falcone, Mathias W Pletz, Alessandra Oliva, Matteo Bassetti, Matthias G Vossen, George Dimopoulos, Claudio M Mastroianni, Thomas Borrmann, Christian Mayer","doi":"10.1007/s40121-026-01413-5","DOIUrl":"10.1007/s40121-026-01413-5","url":null,"abstract":"<p><strong>Introduction: </strong>This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting.</p><p><strong>Methods: </strong>Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response.</p><p><strong>Results: </strong>The subgroup included 161 patients (median age 60 years, 30.4% female, median APACHE II score 15), of whom 59.6% required intensive care, and 41.6% had sepsis at baseline. The most common indications for FOS therapy were hospital-acquired/ventilator-associated pneumonia (28.0%), bacteremia/sepsis (26.1%), and complicated urinary tract infections (24.8%). Infections were predominantly caused by Klebsiella pneumoniae (62.7%), Pseudomonas aeruginosa (28.6%), and Acinetobacter baumannii (17.4%). Carbapenem resistance was mainly mediated by Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM). In the majority of patients, FOS was part of a combination regimen (91.3%), with ceftazidime-avibactam being the most frequently used partner antibiotic. Overall, clinical success was achieved in 79.4% of patients, while the successful clinical response and microbiological cure rates were 87.5% and 81.3% at the end of FOS treatment, respectively. All-cause in-hospital mortality was 9.9%. Electrolyte imbalances were the most commonly reported adverse drug reactions, but they were mostly not treatment-limiting.</p><p><strong>Conclusions: </strong>The real-world data of this subgroup analysis suggest that FOS-containing regimens were associated with generally favorable clinical and microbiological outcomes and acceptable tolerability in patients with severe infections due to CR Gram-negative bacteria.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2751-2771"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase IIa, Proof-of-Concept, Placebo-Controlled, Randomised Trial to Investigate the Efficacy and Safety of Oxfendazole as a Macrofilaricidal Drug in Adults Harbouring Lymphatic Filarial Worms.","authors":"Gunjan Kumar, Ravi Kant, Deepa Joshi, Kavita Singh, Jerin Jose Cherian, Kattula Rao Vinay Rajan, Shikha Malik, Saibal Das, Sudipto Pallab Roy, Vijay Satam, Rishi Tuhin Guria, Dewesh Kumar, Lakhan Majhee, Anjani Kumar, Manjunath Nookala Krishnamurthy, Lokesh Kumar Sharma, Akshata Chaudhary, Ivan Scandale, Sabine Specht, Samir Sahu, Meghanad Meher, Satyasundar Gajendra Mohapatra, Aparna Mukherjee, Taruna Madan Gupta","doi":"10.1007/s40121-026-01419-z","DOIUrl":"10.1007/s40121-026-01419-z","url":null,"abstract":"<p><strong>Introduction: </strong>Lymphatic filariasis (LF) remains a significant public health concern, with India contributing nearly 55% of the global disease burden and placing approximately 487 million people at risk of infection. Despite the success of mass drug administration (MDA) programs in reducing microfilaraemia, the current regimens have limited macrofilaricidal activity, which hinders the achievement of LF elimination goals. The development of safe and effective drugs targeting adult filarial worms is, therefore, a critical priority. This phase IIa, proof-of-concept study aims to evaluate the efficacy, safety, and pharmacokinetic (PK) profile of oxfendazole in adults with confirmed LF. The primary objective is to estimate the proportion of participants with no detectable adult worm motility on ultrasonography (USG) at 6 months post-treatment, serving as a marker of macrofilaricidal efficacy. Secondary objectives include assessment of safety and tolerability, while exploratory objectives involve the characterization of the PK profile of oxfendazole in the study population.</p><p><strong>Methods: </strong>The study is designed as a phase IIa, randomised, double-blind, placebo-controlled trial with three arms. Participants will be randomised to receive either 400 mg or 800 mg of oxfendazole, or a matching placebo, administered orally once daily for five consecutive days. Oxfendazole, a benzimidazole and structural analogue of flubendazole, has shown promising macrofilaricidal activity in preclinical models, demonstrating complete clearance of adult worms in mice. Phase I clinical studies have established its safety and tolerability in humans, supporting its progression to further clinical evaluation. Ethics approval has been obtained by the independent ethics committees (IEC) of all the participating study sites. This study will be performed in accordance with the Helsinki Declaration of 1964 and its later amendments, ICH-GCP, applicable regulatory requirements and approved study protocol. The details of ethics committee approvals are available in the supplementary material.</p><p><strong>Planned outcomes: </strong>The findings from this trial will be pivotal in guiding the clinical development of oxfendazole, particularly in defining an optimal dosing regimen for use as a macrofilaricidal agent. If successful, this intervention could represent a significant advancement toward the elimination of LF. This study supports India's national target to eliminate LF by 2027 and aligns with the World Health Organization's global elimination goal by 2030.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2805-2816"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Plasma GDF-15 Levels are Associated with the Immune Non-Responder Phenotype in People with HIV.","authors":"Aida López López, Jacobo Alonso Domínguez, Inés Martínez Barros, Alexandre Pérez González, Antonio Ocampo, Luis Morano, Noemí Martínez López de Castro, Otilia Bisbal Pardo, Cristina Díez, María Del Mar Arcos Rueda, Ignacio Álvarez-Rodríguez, Irene Portilla-Tamarit, Enrique Bernal-Morell, Luis López Cortés, Ezequiel Ruiz-Mateos, Eva Poveda","doi":"10.1007/s40121-026-01420-6","DOIUrl":"10.1007/s40121-026-01420-6","url":null,"abstract":"<p><strong>Introduction: </strong>Most people with HIV (PWH) achieve immune recovery with antiretroviral therapy (ART); however, a clinically relevant subset, known as immune non-responders (INRs), fails to restore CD4+ T-cell counts despite sustained virological suppression and shows persistent immune dysfunction. Growth differentiation factor 15 (GDF-15), a stress-responsive cytokine associated with inflammation, aging, chronic disease, and multimorbidity, has not been characterized across distinct HIV viro-immunological phenotypes.</p><p><strong>Methods: </strong>We conducted an exploratory cross-sectional study including 80 PWH classified as ART-naïve individuals, virally suppressed INRs, elite controllers (ECs), and ART-treated immune responders (IRs), as well as 20 HIV-negative controls. Plasma GDF-15 levels were measured by immunoassay. Associations with log-transformed GDF-15 concentrations were assessed using multivariable linear regression including age, CD4+ T-cell nadir, and INR status.</p><p><strong>Results: </strong>INRs showed the highest plasma GDF-15 levels (median, 1143.9 pg/ml), significantly exceeding those observed in ART-naïve individuals, ECs, IRs, and HIV-negative controls (all p ≤ 0.002). GDF-15 levels correlated positively with age, time since HIV diagnosis, and ART duration, and inversely with CD4+ T-cell nadir and the CD4/CD8 ratio (all p ≤ 0.001). In adjusted analysis, INR status remained independently associated with higher log-transformed GDF-15 levels (β = 0.271, 95% CI 0.062-0.480; p = 0.012), corresponding to 31.1% higher GDF-15 concentrations relative to non-INR participants.</p><p><strong>Conclusion: </strong>Plasma GDF-15 levels were higher in virally suppressed INRs than in other viro-immunological groups and remained independently associated with INR status after adjustment for selected covariates. These findings support further investigation of GDF-15 as a potential biomarker of incomplete immune recovery and residual biological stress in virally suppressed PWH. Prospective studies are warranted to validate its clinical and pathophysiological relevance.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2793-2804"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness of Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Pneumonia, Time-Stratified Risk Factors for Short- and Long-Term Mortality, and Inpatient Costs: A Multicenter Retrospective Cohort Study.","authors":"Chao Liu, Wei Li, Enjing Zhang, Lei Hu, Yong Li, Ying Chen, Junwei Wang, Yinghao He, Dong Xu, Zhongju Chen, Dong Liu, Yan He","doi":"10.1007/s40121-026-01416-2","DOIUrl":"10.1007/s40121-026-01416-2","url":null,"abstract":"<p><strong>Introduction: </strong>Multidrug-resistant (MDR) Gram-negative pneumonia is associated with high mortality and substantial healthcare resource utilization. Ceftazidime-avibactam (CAZ-AVI) is an important option, yet real-world experience in Chinese pneumonia cohorts is limited and the associated inpatient costs are seldom reported. This study aimed to describe the clinical response to CAZ-AVI in routine practice, to identify the factors associated with 14-day and with 30-day all-cause mortality separately so as to examine how they differ over time, and to characterize inpatient costs.</p><p><strong>Methods: </strong>We retrospectively studied 693 adults with MDR pneumonia who received at least 3 days of CAZ-AVI at eight hospitals in Hubei, China, between August 2022 and August 2025. Factors associated with 14-day and 30-day all-cause mortality were examined by univariable and multivariable logistic regression, with LASSO-penalized regression and cross-validation as a sensitivity analysis. Acute kidney injury (AKI) was recorded as a safety observation, and pneumonia-related inpatient costs were summarized descriptively. The study is reported in line with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).</p><p><strong>Results: </strong>Overall, 480 patients (69.3%) had a favorable response (cure, 356 [51.4%]; improvement, 124 [17.9%]). A higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score was independently associated with mortality at both 14 days (adjusted OR 1.20; 95% CI 1.14-1.26) and 30 days (1.27; 1.18-1.37). At 14 days, death was further associated with bacteremia (4.76; 2.39-9.66), carbapenem-resistant organisms (CRO; 5.93; 2.60-13.60), and septic shock (3.30; 1.32-8.39). At 30 days, the associated factors were Klebsiella pneumoniae (15.19; 3.25-78.94; the wide confidence interval warrants caution) and septic shock (5.74; 1.34-24.97), while a later rise in serum albumin accompanied lower mortality (0.89; 0.82-0.95). AKI occurred in 15 of 693 patients (2.2%). The median total inpatient cost was USD 14,982 (IQR 8462-25,136), of which CAZ-AVI accounted for a median of USD 3901 (IQR 2069-6159).</p><p><strong>Conclusion: </strong>In routine practice, CAZ-AVI for MDR pneumonia was associated with a favorable response, and the factors linked to early death differed from those linked to later death. These associations are hypothesis-generating; together with the cost description, they may help inform time-stratified management and the controlled studies needed to confirm these findings.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2699-2715"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can We Compare Adverse Events' Attributable Risk Using a Self-Controlled Case Series Design for Vaccine Safety? A Guillain-Barré Syndrome Use Case.","authors":"Caihua Liang, Erica L Chilson, Joanne Wu, Scott P Kelly, Qing Liu, Kathleen L Dooling, Maria Maddalena Lino, Joseph A Lewnard, Bradford D Gessner, Elizabeth Begier","doi":"10.1007/s40121-026-01365-w","DOIUrl":"10.1007/s40121-026-01365-w","url":null,"abstract":"<p><strong>Introduction: </strong>Estimating attributable risk (AR) through self-controlled case series (SCCS) analyses alone may limit generalizability because SCCS only incorporate vaccinated patients with the outcome (e.g., Guillain-Barré syndrome [GBS]) who may differ from the recommended vaccinee population. We aimed to demonstrate background event incidence rates' impact on vaccine-specific GBS ARs and to standardize ARs across different vaccine studies by applying a generalizable, population-based GBS background rate to better estimate the expected population-level ARs.</p><p><strong>Methods: </strong>We identified post-licensure SCCS vaccine studies and GBS background rates using US Medicare data via targeted literature review. GBS control period rates from SCCS vaccine studies were extracted or calculated. Population-level ARs were calculated for each vaccine using two published and two hypothetical background GBS rates and the original SCCS-generated incidence rate ratios (IRRs).</p><p><strong>Results: </strong>Published vaccine-specific GBS IRRs ranged from 2.02 (95% CI 0.93-4.40) for RSVpreF to 4.96 (95% CI 1.43-17.27) for recombinant zoster vaccine (RZV). Study-specific ARs per 100,000 doses ranged from 0.28 (H1N1) to 0.90 (RSVpreF). Vaccines with lower control period GBS rates had a lower attributable risk for a given IRR. After standardization using external background GBS rates, population-level ARs were higher for vaccines with higher IRRs. For example, when using the H1N1 vaccine control period rate as the GBS background rate for AR calculation, RSVpreF had the lowest AR per 100,000 doses (0.21) and RZV the highest (2.26).</p><p><strong>Conclusions: </strong>AR calculation is dependent on the control period event rate within a given SCCS analysis. ARs derived exclusively from SCCS analyses may lead to incorrect conclusions regarding an adverse event's absolute risk in regulatory communications due to a lack of external validity. Using a representative background rate from the recommended vaccinee population, along with SCCS-derived IRR, offers a more consistent approach to calculate the expected population-level AR and supports vaccine risk-benefit assessments.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2737-2750"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding \"Adult RSV Vaccination: What is the Role of RSV Subgroup in Disease Prevention?\"","authors":"Harish Madhava, Karin Velthove","doi":"10.1007/s40121-026-01418-0","DOIUrl":"10.1007/s40121-026-01418-0","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2827-2829"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide or Entecavir in Older Patients with Chronic Hepatitis B.","authors":"Federico Cesanelli, Ottavia Nozza, Federica Gottardi, Francesca Mosti, Serena Zaltron, Giorgio Tiecco, Irene Scarvaglieri, Angiola Spinetti, Francesco Castelli, Eugenia Quiros-Roldan","doi":"10.1007/s40121-026-01412-6","DOIUrl":"10.1007/s40121-026-01412-6","url":null,"abstract":"<p><strong>Introduction: </strong>Tenofovir disoproxil fumarate (TDF) is highly effective for chronic hepatitis B (CHB) but may induce progressive renal impairment and proximal tubular dysfunction. Switching to tenofovir alafenamide (TAF) or entecavir (ETV) may reduce TDF-related nephrotoxicity. This study evaluated renal and metabolic changes before and after switching from TDF to TAF or ETV in a real-world cohort of older patients.</p><p><strong>Methods: </strong>This retrospective longitudinal cohort study included adults with CHB who switched from TDF to TAF or ETV at a tertiary center (2012-2023). Eligible patients had ≥ 2 years of TDF treatment and ≥ 2 years of post-switch follow-up. Those with virological failure, major coinfections, or non-HBV-related kidney disease were excluded. Clinical and laboratory data were collected at 6-month intervals from 2 years before to 4 years after switching. Biomarker trajectories were analyzed using linear mixed-effects models with time centered at switch comparing treatments and with multivariable adjustment for key confounders.</p><p><strong>Results: </strong>A total of 102 patients were included (TAF n = 82; ETV n = 20), mean age 72 ± 10 years, 72% male. All patients had undetectable HBV-DNA at switch. During TDF therapy, serum creatinine showed a non-significant increasing trend (β = + 0.008 mg/dL/year, p = 0.24), which persisted after switching (β = + 0.009 mg/dL/year, p = 0.07), with no significant difference between groups. Serum phosphate declined during TDF in the ETV group (β = - 0.175 mg/dL/year, p = 0.002) and showed a significant increase after switching (β = + 0.111 mg/dL/year, p = 0.031) while the TAF group remained stable throughout. Total cholesterol ishowed a significant immediate increase at the time of switch (+ 18.3 mg/dL, 95% CI 11.0-25.6, p < 0.001), with no significant difference between TAF and ETV.</p><p><strong>Conclusions: </strong>Unlike previous studies reporting clear creatinine improvement after switching from TDF, this cohort did not show a statistically significant reduction in creatinine levels after the switch although an attenuation of creatinine progression and recovery of phosphate levels were observed, suggesting mitigation of TDF-related renal and tubular toxicity.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2589-2607"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Bivalent Respiratory Syncytial Virus Prefusion F Vaccine for Older Adults in the Netherlands.","authors":"Annefleur C Langedijk, Floris van den Dungen, Frits M E Franssen, Marco Goeijenbier, Ahuva Averin, Erin Quinn, Mark Atwood, Diana Mendes","doi":"10.1007/s40121-026-01400-w","DOIUrl":"10.1007/s40121-026-01400-w","url":null,"abstract":"<p><strong>Introduction: </strong>Lower respiratory tract disease caused by respiratory syncytial virus (RSV-LRTD) is associated with substantial clinical and economic burden among older adults and adults with chronic medical conditions. Bivalent RSV prefusion F protein-based vaccine (RSVpreF) has been authorized for use among all adults aged ≥ 60 years in the Netherlands, and The Health Council of the Netherlands has recommended RSV vaccination for at-risk persons aged 60-74 years and all persons aged ≥ 75 years. We estimated the cost-effectiveness of implementing this strategy.</p><p><strong>Methods: </strong>We have developed a static cohort model to demonstrate lifetime clinical and economic outcomes associated with RSV-LRTD among adults in the Netherlands, with (vs. without) RSVpreF use (price: €180; age/risk-specific uptake: 44.6-80.4%). Model inputs include population characteristics, disease rates [hospitalization (RSV-H), general practitioner visit (RSV-GP), non-medically attended (RSV-NMA)], fatality rates, vaccine effectiveness (based on real-world and clinical trial data), utilities/disutilities, medical care costs, indirect costs associated with morbidity- and mortality-related productivity loss, and vaccination costs. Discounting was applied to costs (3%) and benefits (1.5%).</p><p><strong>Results: </strong>Among at-risk adults aged 60-74 years and all adults aged ≥ 75 years (n = 4.8 million) in the Netherlands, single-dose RSVpreF would prevent 84,228 RSV-LRTD cases (RSV-H: 16,642, RSV-GP: 21,788, RSV-NMA: 45,798) and 2304 RSV-LRTD deaths over a lifetime horizon. With 11,006 quality-adjusted life-years (QALY) gained and a €195 million increase in total costs, incremental cost-effectiveness ratio for RSVpreF would be €17,740/QALY gained. RSVpreF would thus prevent 16% of hospitalizations, 15% of deaths, 16% of medical costs, and 20% of indirect costs related to RSV among this population over their remaining lifetime. In probabilistic sensitivity analyses applying variability to key inputs, all 1000 replications yielded cost-effectiveness ratios within the Health Council's willingness-to-pay threshold (< €50,000/QALY gained).</p><p><strong>Conclusions: </strong>Findings suggest that RSVpreF would greatly reduce the clinical and economic burden of RSV among older adults in the Netherlands.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2609-2625"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Research on Microecological Landscape for Infection Risk Stratification in Newly Diagnosed Patients with Hematological Conditions.","authors":"Miaoxin Peng, Yueyi Xu, Xuefang Cao, Yizhe Xue, Jie Pang, Shiyuan Zhou, Peipei Xu, Yonggong Yang, Xiaoping Zhang, Jun Qian, Yang Wang, Xuzhang Lu, Yan Wan, Yu Sun, Xiaoying Hua, Yan Xu, Bing Chen, Jian Ouyang","doi":"10.1007/s40121-026-01401-9","DOIUrl":"10.1007/s40121-026-01401-9","url":null,"abstract":"<p><strong>Introduction: </strong>Infection is a common and potentially fatal complication during the treatment of hematological diseases, particularly in the context of chemotherapy-induced immunosuppression. The nonselective use of antibiotic prophylaxis in patients with neutropenia in China has persistently accelerated antimicrobial resistance. Early identification of patients at high risk for infection before clinical symptom onset could enable targeted preventive strategies; however, reliable and biologically informed screening approaches remain limited.</p><p><strong>Methods: </strong>We developed a prediction model for infection risk stratification in newly diagnosed patients with hematological conditions. Plasma metagenomic next-generation sequencing was performed in a prospective cohort of 230 patients. Among them, 116 patients provided prechemotherapy, non-neutropenic plasma samples (cohort A), and 114 patients provided postchemotherapy, neutropenic samples (cohort B). Microbial community profiles were analyzed, and machine learning approaches were applied to construct classifiers for neutropenia status and subsequent infection risk.</p><p><strong>Results: </strong>Plasma metagenomic profiling revealed a complex microecological landscape in patients with hematological conditions and identified distinct microbial features associated with neutropenia. A trained random forest classifier successfully distinguished patients without neutropenia from patients with neutropenia, achieving an area under the receiver operating characteristic curve of 0.8324. Importantly, a microorganism-based random forest model was established to predict patients at high risk of infection, yielding an area under the curve of 0.942. Nested cross-validation demonstrated high classification accuracy, correctly identifying 99.1% of patients who subsequently developed infections and 72.7% of patients who remained infection-free. Furthermore, integration of microbial features with clinical metrics improved predictive performance, resulting in an area under the curve of 0.953.</p><p><strong>Conclusions: </strong>This microorganism-based prediction model provides an effective tool for infection risk stratification in patients with hematological conditions. By enabling early identification of high-risk individuals, the model has potential clinical utility for guiding precise preventive interventions and optimizing infection management strategies, which can significantly reduce the use of prophylactic antibiotics, thereby mitigating the development of resistance.</p><p><strong>Registration number: </strong>ChiCTR2100042992.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2717-2736"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity, Tolerability, and Safety of BA.1-Adapted BNT162b2 Vaccine in 18- to 55-Year-Olds Previously Vaccinated with BNT162b2 or Who Were COVID-19 Vaccine-Naive.","authors":"David Fitz-Patrick, Omair Sahgal, Leon F Fouché, Essack Mitha, Mookho Malahleha, Juleen Gayed, Georgina Keep, Ying Zhang, Kayvon Modjarrad, Todd Belanger, Xia Xu, David Cooper, Federico J Mensa, Uǧur Sahin, Ӧzlem Türeci, Kena A Swanson, Annaliesa S Anderson, Alejandra Gurtman, Nicholas Kitchin","doi":"10.1007/s40121-026-01409-1","DOIUrl":"10.1007/s40121-026-01409-1","url":null,"abstract":"<p><strong>Introduction: </strong>Variant-adapted COVID-19 vaccines can induce more robust immune responses against closely matched circulating variants than original vaccines.</p><p><strong>Methods: </strong>Within a phase 3 master study, monovalent Omicron BA.1-adapted BNT162b2 (BNT162b2-BA.1) was evaluated in healthy BNT162b2-experienced (cohorts 1-2) or COVID-19 vaccine-naive (cohort 3) 18 to 55 year-olds. Primary immunogenicity endpoints in cohort 1 were geometric mean ratios (GMRs) of Omicron BA.1 neutralizing titers 1 month after BNT162b2-BA.1 to those after one BNT162b2 dose and differences in percentages of participants with Omicron BA.1 seroresponse between BNT162b2-BA.1 and BNT162b2. In cohort 2, primary immunogenicity objectives (participants without evidence of previous SARS-CoV-2 infection) were to demonstrate superiority (GMR two-sided 95% CI lower limit > 1) with respect to neutralizing titer levels and noninferiority with respect to seroresponse difference (difference two-sided 95% CI lower limit > - 5%) for BNT162b2-BA.1 versus BNT162b2. In cohort 3, primary immunogenicity objectives were to demonstrate superiority with respect to neutralizing titer levels and noninferiority with respect to seroresponse after two BNT162b2-BA.1 doses compared with participants receiving BNT162b2 in an efficacy trial. Reactogenicity and adverse event frequencies were determined.</p><p><strong>Results: </strong>A total of 1471 participants were included. In cohort 1 (BNT162b2-experienced), GMRs compared with one BNT162b2 dose were 2.87 and 2.64 after one or two BNT162b2-BA.1 doses, respectively, and differences in percentages of participants with seroresponse between BNT162b2-BA.1 and BNT162b2 were 29.0% and 21.0% for one or two BNT162b2-BA.1 doses. In cohort 2 (BNT162b2-experienced), one BNT162b2-BA.1 dose met prespecified superiority and noninferiority criteria with respect to GMR and difference in percentage of participants achieving seroresponse, respectively, compared with BNT162b2. In cohort 3 (COVID-19 vaccine-naive), superiority with respect to GMR and noninferiority with respect to difference in percentage of participants achieving seroresponse of BNT162b2-BA.1 to BNT162b2 were met. BNT162b2-BA.1 and BNT162b2 safety and tolerability profiles were similar.</p><p><strong>Conclusions: </strong>Omicron BA.1-adapted COVID-19 vaccines can broaden immune responses against Omicron BA.1 SARS-CoV-2 variants.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04955626.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2645-2667"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}