Infectious Diseases and Therapy最新文献

{"title":"Detection of a Nirsevimab-Resistant RSV-B Variant (F:K68Q) in an Adult with Severe Infection.","authors":"Nicolas de Prost, Marie Le Goff, Pierre Cappy, Pierre Bay, Mélissa N'debi, Alexandre Soulier, Jean-Michel Pawlotsky, Christophe Rodriguez, Slim Fourati","doi":"10.1007/s40121-026-01442-0","DOIUrl":"10.1007/s40121-026-01442-0","url":null,"abstract":"<p><strong>Introduction: </strong>Respiratory syncytial virus (RSV) is recognized as a major cause of severe disease in adults, particularly those having cardiorespiratory comorbidities or immunosuppression. The recent deployment of monoclonal antibodies targeting the prefusion F protein could be used in the future to prevent RSV-associated hospitalization and critical illness in immunocompromised adult patients.</p><p><strong>Methods: </strong>This report is part of the ongoing ARF-RSV study (NCT06197152), a prospective, multicenter observational cohort.</p><p><strong>Results: </strong>We report on the case of a 64-year-old man with a previous medical history of aggressive mantle cell lymphoma under active treatment who was admitted to the intensive care unit for severe sepsis in the setting of febrile aplasia. Clinical evolution was rapidly favorable, with resolution of hemodynamic failure within a few days. Two nasopharyngeal samples collected 7 days apart were positive for RSV-B. Genetic analysis identified a strain belonging to lineage B.D.E.1, with both samples harboring a dominant F:K68Q substitution in the fusion protein. In the first sample, the mean depth of coverage was over 180× and the F:K68Q substitution was detected at an allele frequency of 99%. In the second sample, collected 7 days later, the mean depth of coverage was 170×, with the same substitution detected with an allele frequency of 97%, consistent with persistence as a dominant variant over time. This substitution has been previously associated with high-level resistance to nirsevimab. More generally, F:K68Q appears to be rare among circulating RSV-B strains based on available global sequence surveillance data (GISAID). Its detection in a monoclonal antibody-naïve patient reinforces the hypothesis that this substitution may circulate independently of nirsevimab exposure.</p><p><strong>Conclusion: </strong>The persistence of a resistant RSV variant in a patient who was immunocompromised without prior exposure to nirsevimab suggests that such variants may circulate and be transmitted. In this context, RSV vaccination of patients who are immunocompromised may not only provide individual protection but also help limit the dissemination of resistant strains.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3221-3226"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968213","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":"Narrative Review of Two-Drug Regimens in Modern HIV Care: Driving Innovation, Flexibility, and Quality of Life.","authors":"Lucia Taramasso, Antonio Di Biagio, Simona Di Giambenedetto, Vincenzo Esposito, Roberta Gagliardini, Giovanni Guaraldi, Camilla Muccini, Diego Ripamonti, Roberto Rossotti, Stefano Rusconi","doi":"10.1007/s40121-026-01430-4","DOIUrl":"10.1007/s40121-026-01430-4","url":null,"abstract":"<p><p>The treatment goals in human immunodeficiency virus (HIV) care have expanded beyond virological suppression to encompass long-term tolerability, treatment satisfaction, adherence, quality of life and person-centred care. Within this evolving framework, two-drug regimens (2DRs) with oral and long-acting drugs have emerged as an important therapeutic strategy, demonstrating high virological efficacy in selected clinical settings, while reducing cumulative drug exposure and expanding treatment options. Dolutegravir/lamivudine, dolutegravir/rilpivirine and long-acting cabotegravir/rilpivirine are the regimens studied the most, supported by randomised trials and real-world evidence. Beyond efficacy, 2DRs can improve flexibility of care, support adherence, reduce treatment burden and positively affect patient-reported outcomes. Long-acting injectable strategies may be particularly valuable for individuals who face challenges with daily oral adherence or treatment-related stigma. This narrative review summarizes current evidence on the role of oral and injectable 2DRs in key domains including innovation, flexibility, tolerability, adherence and quality of life, while discussing current limitations and future perspectives.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2865-2894"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955341","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":"Pharmacokinetics, Safety, and Exploratory Efficacy of Onradivir in Children with Acute Uncomplicated Influenza: A Multicenter, Dose-Ranging, Phase 2 Study.","authors":"Qiang Qin, Chunying Ma, Yimin Yang, Haijun Li, Suiqi Xu, Yongxue Chi, Zhengzhen Tang, Sanjing Li, Xiaoxin Chen, Wei Zhao, Baoping Xu","doi":"10.1007/s40121-026-01432-2","DOIUrl":"10.1007/s40121-026-01432-2","url":null,"abstract":"<p><strong>Introduction: </strong>Seasonal influenza brings high morbidity and mortality in children, with current antivirals limited by low efficacy and rising resistance. Onradivir (ZSP1273), a polymerase basic protein 2 (PB2) cap-binding inhibitor effective in adults, remains unstudied in pediatric influenza A. This phase 2 study evaluated its safety, pharmacokinetics, and preliminary efficacy in affected children.</p><p><strong>Methods: </strong>This multicenter randomized open-label phase 2 trial enrolled children under 18 years with confirmed influenza A at 31 Chinese sites. Participants were 1:1 randomized to 5-day high-dose or low-dose onradivir granules stratified by age and weight. Primary endpoints covered safety and steady-state pharmacokinetics; exploratory outcomes included symptom relief, fever resolution, viral kinetics, and exposure-response correlation.</p><p><strong>Results: </strong>Seventy-two participants were enrolled and randomized; 70 entered the intention-to-treat infected population. The high-dose regimen achieved systemic exposures matching efficacious adult targets. Onradivir was well tolerated: most adverse events were mild or moderate, with no serious adverse events or adverse events leading to treatment discontinuations; gastrointestinal events were mild and infrequent. Median symptom alleviation was 28.6 h (95% confidence interval 17.9-59.1) high dose vs. 33.7 h (19.4-42.7) low dose. Influenza A viral ribonucleic acid declined rapidly, falling 1.5 log10 copies/ml at 24 h and 2.4 log10 copies/ml by day 5. No resistance-associated PB2 substitutions were detected. Analyses showed a flat exposure-response relationship across clinical and virological endpoints.</p><p><strong>Conclusion: </strong>Onradivir was well tolerated, achieved adult-equivalent exposure, and was associated with rapid symptom resolution and viral suppression. These findings support the selected pediatric dosing strategy and warrant confirmatory comparative trials.</p><p><strong>Trial registration number: </strong>NCT06656026.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3101-3118"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955344","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":"Diagnostic Performance of Machine Learning Models for Predicting Bloodstream Infections in Large Cohorts: A Systematic Review and Meta-analysis.","authors":"Daniele Roberto Giacobbe, Elena Ceccardi, Marco Muccio, Mariano Nobile, Lucia Scarfone, Alberto Enrico Maraolo, Ivan Gentile, Matteo Bassetti","doi":"10.1007/s40121-026-01421-5","DOIUrl":"10.1007/s40121-026-01421-5","url":null,"abstract":"<p><strong>Introduction: </strong>Machine learning (ML) models have been increasingly applied to support the diagnosis of bloodstream infections (BSI), particularly through the analysis of large routinely collected healthcare datasets. However, it remains uncertain whether large sample sizes alone are sufficient to achieve high diagnostic accuracy. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of ML-based models for BSI in large cohorts.</p><p><strong>Methods: </strong>MEDLINE, Embase, and Web of Science were systematically searched from inception to December 31, 2025 (Prospero registration CRD420251080948). We included observational studies evaluating ML models for BSI diagnosis with ≥ 1000 patients or BSI episodes and reporting sufficient data to reconstruct diagnostic accuracy measures. Pooled sensitivity and specificity were estimated using a bivariate random-effects Reitsma model. Secondary analyses included pooled area under the summary receiver operating characteristic curve (SROC-AUC), predictive values, subgroup analyses, and meta-regression.</p><p><strong>Results: </strong>Twenty-four retrospective studies were included. Most studies evaluated adult hospitalized patients and used routinely collected structured data, including laboratory, vital sign, and administrative variables. Tree-based ensemble algorithms were the most commonly used architectures. The pooled sensitivity and specificity were 76.6% (95% CI 66.1-84.7%) and 84.5% (95% CI 75.4-90.7%), respectively, with an SROC-AUC of 0.87. The pooled prevalence of BSI was 9.5%, corresponding to pooled positive and negative predictive values of 34.2% and 97.2%, respectively. Significant inter-study heterogeneity was observed (I² = 74%).</p><p><strong>Conclusions: </strong>ML-based models demonstrated good overall diagnostic performance for predicting BSI, but accuracy remains insufficient to solidly support clinical decision-making at the present time. These findings may suggest that increasing dataset size alone could not overcome limitations related to the limited clinical granularity of routinely extracted structured data.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2895-2925"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850514","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 Fostemsavir in Individuals with Multidrug-Resistant HIV-1, Stratified by Baseline Viral Load.","authors":"Manyu Prakash, Alftan Dyson, Fangfang Du, Bo Li, Marcia Wang, Michelle Moorhouse, Bruce Gilliam, Bryn Jones","doi":"10.1007/s40121-026-01343-2","DOIUrl":"10.1007/s40121-026-01343-2","url":null,"abstract":"<p><strong>Introduction: </strong>In populations with undetectable or low viral load (VL) and limited treatment options, antiretrovirals with a new mechanism of action may support HIV-1 treatment success. We evaluated efficacy and safety of fostemsavir-based regimens in participants with limited treatment options and an undetectable or low baseline VL from the phase 3 BRIGHTE study.</p><p><strong>Methods: </strong>BRIGHTE included adults with multidrug-resistant HIV-1 on failing regimens with ≤ 2 fully active antiretrovirals remaining. Participants with 1-2 fully active antiretrovirals entered the randomized cohort and received open-label fostemsavir + optimized background therapy after an 8-day placebo-controlled period. This post hoc analysis assessed virologic suppression (VL < 40 copies/mL; missing = excluded), immunologic outcomes, and safety through week 240 by baseline VL (< 40, 40 to < 400, 400 to < 1000, and ≥ 1000 copies/mL).</p><p><strong>Results: </strong>In the randomized cohort (N = 272), 21 (8%) participants had baseline VL < 400 copies/mL, 2 with < 40 copies/mL. By week 24, 13/18 (72%), 8/10 (80%), and 121/219 (55%) participants in the < 400, 400 to < 1000, and ≥ 1000 copies/mL subgroups, respectively, had virologic suppression. At week 240, 14/14 (100%) participants with baseline VL < 400 copies/mL were suppressed. In the overall randomized cohort, CD4⁺ T cell count (P < 0.001) and CD4⁺/CD8⁺ ratio (P < 0.001) demonstrated a significant increase from baseline through week 240. Mean change from baseline to week 240 in CD4⁺ T cell count was + 294 and + 141 cells/mm³ in the < 40 and 40 to < 400 copies/mL subgroups, respectively. Mean CD4⁺/CD8⁺ ratio was 0.62 at baseline and 0.79 at week 240 in the < 40 copies/mL subgroup and 0.34 at baseline and 0.62 at week 240 in the 40 to < 400 copies/mL subgroup. Few adverse events leading to withdrawal/discontinuation were observed in the < 40 copies/mL (0/2) or 40 to < 400 copies/mL (1/19 [5%]) subgroups.</p><p><strong>Conclusion: </strong>Findings support considering fostemsavir for regimen optimization in individuals with limited treatment options and undetectable/low VL, especially if safety/tolerability may be a concern.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT02362503.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3119-3134"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955283","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":"Live Attenuated Influenza Vaccine (LAIV) for Children for the Prevention of Influenza Illness in Sweden: A Cost-Effectiveness Analysis.","authors":"Petter Brodin, Fryderyk Wilczyński, Luca Ricci Pacifici, Peter D Gabb, Holly Prudden, Giorgia Magnatti, Sara Hallberg, Mikko Tuovinen, Åsa Tormod, Amy Zhou, Klas Bergenheim","doi":"10.1007/s40121-026-01429-x","DOIUrl":"10.1007/s40121-026-01429-x","url":null,"abstract":"<p><strong>Introduction: </strong>Both inactivated influenza vaccine and live attenuated influenza vaccine (LAIV) (indicated for use in children aged 2-17 years) effectively prevent influenza transmission and related outcomes. Despite high transmission among children, vaccination practices in Sweden focus primarily on targeting individuals at higher risk of influenza-related illness and mortality, including older adults. The objective of this study was to assess the cost-effectiveness of increasing LAIV coverage among children aged 2-17 years.</p><p><strong>Methods: </strong>We developed a de novo health economic model (HEM) that included a dynamic transmission model (DTM) component to estimate population-level outcomes for a typical influenza season in Sweden. The DTM implemented a compartmental structure to model the prevalence of three influenza strains over a 1-year time horizon. The HEM used a decision-tree structure to translate epidemiological outputs into clinical and economic outcomes. The model simulated theoretical vaccination scenarios, comparing a reference scenario based on historical vaccination coverage with an intervention with LAIV in which coverage among children aged 2-17 years was increased from 0.36% to 25%.</p><p><strong>Results: </strong>Increasing the uptake of LAIV in 2-17-year-olds could prevent a further 505,824 influenza infections in a typical season, two-thirds of which would be prevented in the indirect population (adults and children aged < 2 years). The model estimated this to translate into 33,419 fewer cases requiring medical attention, of which 1929 were hospitalizations, ultimately preventing 193 intensive care unit admissions and 99 deaths. The intervention scenario was considered cost-effective from a payer perspective (direct costs only; incremental cost-effectiveness ratio of SEK 73,266 per quality-adjusted life year) and dominant (cost-saving) from a societal perspective. Sensitivity and scenario analyses showed that results were robust to changes in key model parameters, maintaining cost-effectiveness.</p><p><strong>Conclusions: </strong>In Sweden, the implementation of LAIV is estimated to be cost-effective in 2-17-year-olds by reducing disease burden and healthcare costs in both children and the broader population.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2977-3002"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857417","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":"Ceftazidime-Avibactam With or Without Aztreonam Versus Other Active Antimicrobials in the Treatment of Bloodstream Infections by Carbapenem-Resistant Klebsiella pneumoniae.","authors":"Rodrigo C da Fonseca, Beatriz Arns, Adriana Schmidt, Emerson Dos S Hoffmann, Nadiana Inocente, Amanda de F Balbinot, Erik M Martins, Jaysa Pizzi, Guilherme G L Sório, Renata D F Klafke, Luiza M Perez, Letícia C Marinho, Cristiane T da S Kawski, Alexandre P Zavascki","doi":"10.1007/s40121-026-01440-2","DOIUrl":"10.1007/s40121-026-01440-2","url":null,"abstract":"<p><strong>Introduction: </strong>Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs) are associated with high mortality and limited treatment options. Evidence supporting ceftazidime-avibactam, with or without aztreonam, from studies exclusively with BSIs caused by CRKP remains scarce, particularly from Latin America, where there is a high burden of disease. In this study, we compared ceftazidime-avibactam-based regimens with other active antimicrobials (OAA) regimens for healthcare-associated CRKP BSIs in a Brazilian tertiary-care hospital.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study including consecutive adult patients with healthcare-associated BSIs caused by CRKP between 2014 and 2024. Patients receiving ceftazidime-avibactam with or without aztreonam were compared with those receiving OAAs. The primary outcome was 30-day all-cause mortality. Secondary outcomes included acute kidney injury (AKI), the composite of death or AKI, and post-BSI length of hospital stay. Multivariable Cox regression was performed.</p><p><strong>Results: </strong>A total of 129 patients were included, of whom 73 received ceftazidime-avibactam-based therapy and 56 received OAAs. Carbapenemase types included class A (82.2%), class B (9.3%), and class A+B co-producing isolates (8.5%). Thirty-day mortality was significantly lower in the ceftazidime-avibactam group than in the OAA group (23.3% vs. 41.1%; P = 0.049). After adjustment, ceftazidime-avibactam-based therapy remained independently associated with lower 30-day mortality (hazard ratio, 0.51; 95% confidence interval, 0.27-0.96; P = 0.04). The composite of death or AKI was also significantly lower with ceftazidime-avibactam-based therapy (P = 0.047), whereas median post-BSI hospital stay among survivors was 8 days shorter (P = 0.06).</p><p><strong>Conclusions: </strong>In this cohort, ceftazidime-avibactam with or without aztreonam was independently associated with lower 30-day mortality than OAAs in the treatment of CRKP BSIs. These findings extend the available evidence to BSIs caused by carbapenemase-producing isolates and support the need for broader access to ceftazidime-avibactam-based regimens in low- and middle-income countries, where therapeutic options remain limited.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3135-3150"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976848","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 Therapy with Eravacycline for Complex Infections Caused by Carbapenem-Resistant Pathogens with a Focus on Patients with Severe Burns.","authors":"Sven Kalbitz, Kathrin Marx, Jochen Gille, Christoph Lübbert","doi":"10.1007/s40121-026-01431-3","DOIUrl":"10.1007/s40121-026-01431-3","url":null,"abstract":"<p><strong>Introduction: </strong>The purpose of this study was to describe the clinical outcomes in patients with complex infections caused by carbapenem-resistant pathogens who were treated with eravacycline (ERV) containing regimens.</p><p><strong>Methods: </strong>A retrospective chart review was conducted at Hospital St. Georg in Leipzig, Germany, a municipal tertiary care center with specialized departments for infectious diseases and tropical medicine, septic surgery, and severe burn injuries, between 1 January 2023 and 31 December 2025.</p><p><strong>Results: </strong>Eight patients (median age 38 years, 75% male) with bloodstream infections, hospital-acquired pneumonia, complex skin and soft tissue infections, and osteomyelitis were identified. Underlying conditions included severe burns, multiple myeloma, and human immunodeficiency virus (HIV) infection. The causative pathogens were carbapenemase-producing Klebsiella pneumoniae (KPC-2, NDM-1, and OXA-48) and carbapenemase-producing Acinetobacter baumannii (OXA-23, OXA-40, OXA-58, and OXA-72), including strains that expressed multiple carbapenemases. The minimum inhibitory concentrations (MICs) for ERV ranged from < 0.12 to 1.0 µg/mL. Five patients received monotherapy with ERV (100 mg twice per day (BID) intravenous (IV)), and three patients received combination therapy at the same dose along with other antimicrobial agents (ceftazidime/avibactam, sulbactam, and gentamicin). The median duration of treatment with ERV was 10 days (range 5-42 days). Clinical cure was achieved in 87.5% of patients (7/8), and all patients-with the exception of one patient with major skin and soft tissue defects and osteomyelitis-showed evidence of microbiological pathogen eradication, apart from extensive burn wounds. ERV at an increased standard dose of 100 mg BID IV was well tolerated, and no adverse events leading to treatment discontinuation were reported.</p><p><strong>Conclusions: </strong>In this small retrospective study presenting preliminary real-world observational data, ERV proved to be a safe and promising treatment option for complex infections caused by carbapenemase-producing Klebsiella pneumoniae and Acinetobacter baumannii strains, characterized by few side effects and good efficacy even outside indications specified in the approval studies.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3191-3210"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850539","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":"URICA Study: Diagnosis and Management of Recurrent Acute Bacterial Cystitis in Women With Urinary Behavioral Therapy.","authors":"Tanguy Maurice, Orane Lemetayer, Aurélien Binet, Céline Bonduelle, Albert Sotto, Maxime Vallée","doi":"10.1007/s40121-026-01444-y","DOIUrl":"10.1007/s40121-026-01444-y","url":null,"abstract":"<p><strong>Introduction: </strong>Recurrent cystitis (RC) impacts both individual and societal levels due to the associated antibiotic prescriptions. However, the diagnosis is sometimes made incorrectly. The aim of this study was to evaluate the final diagnosis retained and the effectiveness of specific management through urinary behavioral therapy (UBT) in a cohort of women consulting for urinary tract infections (UTI).</p><p><strong>Methods: </strong>This was an observational, retrospective, bi-centric study including women consulting for UTI between March 2019 and August 2024. A total of 255 patients were identified, excluding men and pyelonephritis cases, while including 176 women consulting for RC. In the event of an acquired functional lower urinary tract dysfunction, treatment was managed by means of UBT (voiding volume <400 ml, interval between two voids < 4 h, 24-h voided volume ≥ 1.5 L and ≤ 2 L).</p><p><strong>Results: </strong>A total of 77 patients (45%) had a confirmed diagnosis of RC with no other associated diagnosis. Urethral burning during urination was found in 66 (86%) patients diagnosed with \"isolated RC.\" Among the patients diagnosed with isolated RC, 52 were followed for 4 months or more, and therapeutic UBT was proposed to 30 of these patients, with complete disappearance of RC in 17 (56.7%) and partial recovery in 11 (36.7%). Among the patients (n = 109) followed for at least 4 months (median: 7 months), regardless of diagnosis, 92 (84.4%) achieved complete or partial recovery after appropriate management of the pathology.</p><p><strong>Conclusion: </strong>In our cohort, 55% of patients consulting for RC ultimately had an alternative diagnosis. In cases of functional RC, UBT resulted in complete or partial improvement in 93% of the women followed for more than 4 months.</p><p><strong>Trial registration: </strong>Approved by the French Data Protection Authority (CNIL, Commission Nationale de l'Informatique et des Libertés) and registered under number 30802498.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3169-3180"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008407","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":"Safety, Pharmacokinetics, and Predicted Neutralizing Activity of the SARS-CoV-2 Monoclonal Antibody Sipavibart: Results from Little DIPPER and the SUPERNOVA Substudy.","authors":"Huixia Zhang, Lindsay Clegg, Sam Matthews, Yue Chang, Anastasia A Aksyuk, Dave Francisco, Sambuddha Ghosh, Karina Soboleva, Aashima Puri, Mayur Ramesh, Michael Gibbs, Lee-Jah Chang, Taylor S Cohen","doi":"10.1007/s40121-026-01423-3","DOIUrl":"10.1007/s40121-026-01423-3","url":null,"abstract":"<p><strong>Introduction: </strong>The rapid evolution of SARS-CoV-2 has necessitated efforts to accelerate the clinical evaluation of neutralizing monoclonal antibodies. Little DIPPER and the SUPERNOVA substudy explored the feasibility of immunobridging efficacy from tixagevimab-cilgavimab to sipavibart using predicted neutralizing antibody (nAb) titers.</p><p><strong>Methods: </strong>The randomized, phase 1, Little DIPPER study evaluated the safety and pharmacokinetics of intramuscular (300 mg or 600 mg) and intravenous (300 mg, 600 mg, or 1200 mg) sipavibart in healthy participants. The randomized, phase 2, SUPERNOVA substudy evaluated the safety, predicted nAb activity, and pharmacokinetics of intravenous sipavibart 1200 mg and intramuscular tixagevimab-cilgavimab 300 mg in immunocompetent and immunocompromised individuals. Predicted nAb titers at day 29 for sipavibart against SARS-CoV-2 BA.2.86 and for tixagevimab-cilgavimab against SARS-CoV-2 Alpha were compared in a noninferiority analysis.</p><p><strong>Results: </strong>In Little DIPPER, 96 participants received sipavibart (n = 80) or placebo (n = 16). Through day 91, adverse events (AEs) occurred in 23 participants (28.8%) who were administered sipavibart and one (6.3%) who was administered placebo. Sipavibart exhibited dose-proportional increases in serum exposure following intramuscular or intravenous administration. In the SUPERNOVA substudy, 468 participants received sipavibart (n = 310) or tixagevimab-cilgavimab (n = 158). Through day 29, AEs occurred in 81 participants (26.1%) who were administered sipavibart and 33 (20.9%) who were administered tixagevimab-cilgavimab. No serious hypersensitivity reactions occurred. The ratio of predicted nAb titers for sipavibart against BA.2.86 to tixagevimab-cilgavimab against Alpha (4.07) met noninferiority (90% confidence interval 3.71-4.46 [lower limit > 0.8]) and superiority (95% confidence interval 3.65-4.53 [lower limit > 1.0]) criteria. Serum sipavibart exposures were similar between immunocompetent and immunocompromised participants.</p><p><strong>Conclusion: </strong>These results demonstrate the feasibility and appropriateness of conducting phase 1 and 2 studies to support rapid immunobridging analyses, and accelerate the delivery of new SARS-CoV-2-neutralizing monoclonal antibodies to immunocompromised individuals.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifiers: NCT05872958, NCT05648110.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"3033-3055"},"PeriodicalIF":5.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906047","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}