Infectious Diseases and Therapy最新文献

{"title":"Real-World Multicenter Study on the Effectiveness of Dolutegravir Plus Lamivudine in Treatment-Naive People Living with HIV with Baseline HIV-1 RNA > 500,000 Copies/mL.","authors":"Bichen Xue, Rui Jiang, Yanyun Dou, Jinglan Lai, Wei Zou, Yingjie Fang, Weiguang Feng, Fuyan Sun, Chunhui Yan, Tao Guo, Jian Ao, Ke Hong, Yuhong Xiong, Qi Chen, Chunhua Xu, Guangyong Xu, Xiaoshui Lu, Yuanyuan He, Yirong Shi, Xiaoyan Yang, Yahong Chen, Jiuyun Luo, Baofang Yang, Yanhua Fu, Fang Zhao, Jin Li, Jun Chen","doi":"10.1007/s40121-026-01385-6","DOIUrl":"10.1007/s40121-026-01385-6","url":null,"abstract":"<p><strong>Introduction: </strong>Dolutegravir (DTG) plus lamivudine (3TC) is one of the preferred treatment regimens for HIV, yet evidence remains limited for people living with HIV (PLWH) with high baseline viral load. This study aims to evaluate the effectiveness of DTG/3TC in treatment-naive PLWH with baseline viral load > 500,000 copies/mL in China.</p><p><strong>Methods: </strong>In this real-world multicenter cohort study, PLWH with baseline viral load (VL) > 500,000 copies/mL who initiated DTG/3TC were recruited across 18 clinical sites in China. Matched participants from the same sites with lower baseline VL were also included as a control group. Participants were followed for 48 weeks. The primary endpoint was virological suppression (HIV-1 RNA < 50 copies/mL) at week 48 using the US Food and Drug Administration snapshot algorithm.</p><p><strong>Results: </strong>Of the 375 PLWH enrolled, 150 were classified into the high VL group and 225 into the low VL group. Baseline median HIV-1 RNA was 5.99 and 5.07 log₁₀ copies/mL, respectively. At week 48, virologic suppression was achieved in 88.0% (95% CI 82.8-93.2%) of the high VL group and 92.0% (95% CI 87.9-96.2%) of the low VL group (P = 0.233); 7.5% and 4.0% of participants in the high and low VL groups had plasma HIV-1 RNA ≥ 50 copies/mL, respectively. Median CD4 increases from baseline to week 48 were 153.5 and 147.0 cells/μL in the high and low VL groups, respectively (P = 0.408). Safety profiles were comparable, with one grade 3 adverse event in each group.</p><p><strong>Conclusions: </strong>DTG/3TC showed favorable virological and safety outcomes in treatment-naive PLWH with baseline HIV-1 RNA > 500,000 copies/mL, suggesting that it may be a viable option for PLWH with high baseline viral load.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry: ChiCTR2300074854.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2167-2180"},"PeriodicalIF":5.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13350765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283468","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":"Ceftaroline for Methicillin-Resistant Staphylococcus aureus Endovascular Infection.","authors":"Reese A Cosimi, Kelsey Peña, John L Lock, Todd Riccobene, Bhavik Nana, George Sakoulas","doi":"10.1007/s40121-026-01353-0","DOIUrl":"10.1007/s40121-026-01353-0","url":null,"abstract":"<p><p>Methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections are associated with high mortality. The increasing reports of clinical failure and toxicities associated with first-line vancomycin provide a medical need for alternative therapies. In this narrative review, we analyze studies published from 2017 to 2025 on the efficacy and tolerability of ceftaroline, a β-lactam antibiotic with anti-MRSA activity, for off-label treatment of endovascular infections. Identified publications included 1 randomized controlled trial (RCT), 17 retrospective cohort studies, four case series, and one meta-analysis. Failure rates were similar between ceftaroline, vancomycin, and daptomycin when used as monotherapies. Ceftaroline, used in combination with vancomycin or daptomycin, showed efficacy and tolerability in high-risk MRSA bacteremia cases. Although higher-level evidence is needed to definitively establish ceftaroline as a mainstay treatment of MRSA endovascular infections, the current evidence positions ceftaroline as one of several antibiotic strategies in serious cases of MRSA endovascular infections.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1803-1825"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972386","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":"Severity of COVID-19 Omicron Variants: A Global Systematic Review.","authors":"Deepa Malhotra, Rajeev M Nepal, Irini Zografaki, Moe H Kyaw, Pinelopi Nikolopoulou, Rodrigo Sini de Almeida, Santiago M C Lopez, Stephen Wiblin, Fraser Williams, Sophie Pope, Isabelle Whittle, Fiona Pearson, Daniel Curcio","doi":"10.1007/s40121-026-01352-1","DOIUrl":"10.1007/s40121-026-01352-1","url":null,"abstract":"<p><strong>Introduction: </strong>The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the need to update evidence on coronavirus disease 2019 (COVID-19) severity and disease burden, and better understand the impact on prevention, treatment, and healthcare systems.</p><p><strong>Methods: </strong>This systematic review aimed to determine relative disease severity, through comparative measures of hospitalization, intensive care unit admission and mortality, between SARS-CoV-2 variants of concern emerging since Omicron was first identified. A protocol was registered a priori (PROSPERO ID: CRD42024619193). Systematic searches of MEDLINE and EMBASE databases were conducted in November 2024 and supplemented by conference searches from 2022-2024. Population, Exposure, Comparisons, Outcomes (PECO) criteria were used to screen publications for inclusion. Critical appraisal tools published in the Joanna Briggs Institute (JBI) Handbook for Evidence Synthesis were used to assess the risk of bias of the primary studies included. The outcomes associated with Omicron variants, identified by sequencing or predominance periods, included hospitalization, admission to intensive care, death, and various composite endpoints.</p><p><strong>Results: </strong>Thirty-two studies fulfilled the eligibility criteria, most reported on relative disease severity for early Omicron BA.5 (n = 23) and XBB (n = 24) variants. Overall, COVID-19 severity appeared largely comparable across the various Omicron subvariants. Among the subset of studies that directly compared various severity outcomes to earlier SARS-CoV-2 variants (n = 7), some reported modest increases or decreases in severity. However, these differences were generally not statistically significant. Five studies stratifying outcomes by the presence of comorbid conditions noted that comorbidities were predictors of significantly worse COVID-19 disease outcomes (p = 0.000-0.027).</p><p><strong>Conclusions: </strong>Overall, this systematic review found the severity of COVID-19 disease to be comparable among Omicron subvariants. As SARS-CoV-2 subvariants continue to emerge, these results highlight the continuing need for vaccination against SARS-CoV-2 infection alongside early antiviral intervention to support short-term management and long-term reduction of COVID-19-associated morbidity and mortality.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1827-1849"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963571","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":"Death and ICU Admission Associated with Sars-Cov-2 Variants in Immunocompromised Hospitalised Individuals: A National Observational Study.","authors":"Antônio José Cordeiro Mattos, Francisco Jose Nigro Mazon, Lucas Ferreira Theotonio Dos Santos, Juares Ednaldo Romero Bianco, Frederico Monfardini, Gustavo Prado Dos Santos, Lívia Dias de Sousa, Mariana Martins Sasse, Luiz Vicente Rizzo, Henrique Andrade R Fonseca","doi":"10.1007/s40121-026-01355-y","DOIUrl":"10.1007/s40121-026-01355-y","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals who are immunocompromised (IC) with COVID-19 have consistently been associated with worse clinical outcomes than individuals who are non-immunocompromised (non-IC). The aim of this study was to describe and compare in-hospital outcomes between individuals who are IC and non-IC hospitalised with COVID-19, with a particular focus on mortality across periods defined by the predominant circulating SARS-CoV-2 variants.</p><p><strong>Methods: </strong>This is an observational, retrospective, descriptive study based on a secondary database from Brazil's Unified Health System. Patients hospitalised with laboratory-confirmed COVID-19 were included. Descriptive statistics were used to summarize the cohort; categorical variables were expressed as frequencies and percentages, and continuous variables as mean ± standard deviation. Univariate logistic regression analyses were conducted to estimate the association between immunocompromised status and two key outcomes: in-hospital mortality and ICU admission, stratified by dominant SARS-CoV-2 variant. Results were reported as odds ratios (OR) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Between March 2020 and July 2023, 361,898 hospitalised COVID-19 individuals were identified, with 2.07% (n = 7484) classified as IC. Those individuals consistently exhibited higher odds of death and ICU admission across all SARS-CoV-2 variant periods. The odds of in-hospital mortality ranged from OR: 1.20 (95% CI 1.04-1.39) during the original (WT) variant to OR: 2.39 (95% CI 1.54-3.71) during the Omicron XBB subvariant period; however, the absolute number of cases and deaths for XBB was small, and this OR might have limited clinical significance. The second highest risk for mortality was observed during the Delta wave (OR: 2.16; 95% CI 1.94-2.41), with a much greater number of cases and clinical significance.</p><p><strong>Conclusion: </strong>Immunocompromised status was independently associated with higher odds of adverse hospital outcomes, including ICU admission and in-hospital mortality, regardless of the circulating SARS-CoV-2 variant.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1851-1868"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948500","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":"Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed HIV-1 Infected Adults with TDF-Related Renal or Bone Toxicity.","authors":"Zhenyan Wang, Li Liu, Jun Chen, Jiangrong Wang, Yinzhong Shen, Tangkai Qi, Yang Tang, Wei Song, Jianjun Sun, Shuibao Xu, Junyang Yang, Youming Chen, Yueming Shao, Renfang Zhang","doi":"10.1007/s40121-026-01363-y","DOIUrl":"10.1007/s40121-026-01363-y","url":null,"abstract":"<p><strong>Introduction: </strong>Long-term use of tenofovir disoproxil fumarate (TDF) is associated with renal tubular dysfunction and bone mineral loss. In virologically suppressed people living with HIV (PLWH), optimizing antiretroviral therapy requires maintaining viral suppression while minimizing cumulative drug-related toxicity. We therefore evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) in Chinese PLWH with TDF-related renal or bone toxicity.</p><p><strong>Methods: </strong>This prospective, single-center, open-label cohort study enrolled adults with HIV-1 RNA < 40 copies/ml for ≥ 6 months on TDF-based regimens and evidence of TDF-associated renal or bone toxicity. Participants were switched to DTG/3TC and followed for 48 weeks. The primary endpoint was virological failure at week 48 (FDA Snapshot algorithm). Secondary endpoints included changes in CD4 + T-cell counts, renal tubular biomarkers, bone mineral density (BMD), metabolic parameters, and safety outcomes.</p><p><strong>Results: </strong>One hundred participants were enrolled; 91 completed the study per protocol. Median age was 45 years and 90% were male. At week 48, virological suppression was maintained in 90% of the intention-to-treat-exposed population and 99% of the per-protocol population. CD4 + T-cell counts increased significantly at week 48 (+ 77.4 cells/μl; p < 0.001). Markers of proximal tubular dysfunction improved significantly, including reductions in urinary β2-microglobulin-to-creatinine ratio, urine albumin-to-creatinine ratio, and urinary retinol-binding protein-to-creatinine ratio (all p < 0.001). BMD increased in the lumbar spine and hip (both p < 0.001). Modest weight gain (+ 2.17 kg) and small increases in total cholesterol and low-density lipoprotein cholesterol were observed at week 48.</p><p><strong>Conclusions: </strong>In virologically suppressed Chinese PLWH with TDF-related renal or bone toxicity, switching to DTG/3TC maintained viral suppression and was associated with significant improvements in renal tubular and bone metabolic markers over 48 weeks. DTG/3TC represents a well-tolerated toxicity-driven switch strategy in routine clinical practice.</p><p><strong>Trial registration: </strong>ClinicalTrial.gov ID: NCT05493969.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1913-1924"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981596","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":"Economic Evaluation of PCV21 Use in Populations with Increasing Serotype 4 Invasive Pneumococcal Disease in the US: An Attributable Fraction Threshold Analysis.","authors":"Zinan Yi, Kwame Owusu-Edusei, Elmira Flem, Kristen Feemster, Elamin H Elbasha","doi":"10.1007/s40121-026-01364-x","DOIUrl":"10.1007/s40121-026-01364-x","url":null,"abstract":"<p><strong>Introduction: </strong>The 21-valent pneumococcal conjugate vaccine (PCV21) covers 83-88% of IPD in US adults but does not include serotype 4 (ST4), which is covered by previously recommended vaccines (PPSV23, PCV15, PCV20). Recent increases in IPD cases due to ST4 have been observed, particularly among adults under 65, including Native American/Alaskan Native and those with social risk factors. As a result, the Advisory Committee on Immunization Practices (ACIP) recommends ST4-containing vaccines (PPSV23, PCV15, and PCV20) for populations with ≥ 30% ST4 IPD cases. In this study, we aimed to analyze ST4 attributable fraction (AF) thresholds for health and economic outcomes of PCV21 versus PCV20 vaccination in US adults aged 19-49 and 50-64 years with underlying medical conditions.</p><p><strong>Methods: </strong>We used a validated Markov model to estimate incremental cost-effectiveness ratios (ICERs) for PCV21 versus PCV20 and identified ST4 AF thresholds in which the ICER shifted from 'cost-saving' to 'not cost-effective'. The analysis involved a hypothetical 1 million at-risk adults aged 19-49 and 50-64 years.</p><p><strong>Results: </strong>PCV21 remained cost-saving compared to PCV20 when ST4 accounted for ≤ 27% (age 19-49) or ≤ 36% (age 50-64) of IPD. When ST4 increases were applied to both IPD and NBPP, these thresholds decreased to ≤ 21% and ≤ 28%, respectively.</p><p><strong>Conclusion: </strong>For populations experiencing moderate increases in the proportion of ST4 (i.e., < 30%), PCV21 may offer health and economic benefits over PCV20 for US adults aged 19-64 years with underlying medical conditions. However, in populations with ≥ 30% ST4, ST4-containing vaccines should be used as per ACIP guidance.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1893-1912"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972347","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":"Burden of Invasive Pneumococcal Disease and Community-Acquired Pneumonia in Adults: Significant Adverse Outcomes and Costs beyond Direct Treatment.","authors":"Jenni Kononoff, Veli-Jukka Anttila, Peter Klemets, Marita Kalaoja, Mari Pölkki, Maarit J Korhonen","doi":"10.1007/s40121-026-01357-w","DOIUrl":"10.1007/s40121-026-01357-w","url":null,"abstract":"<p><strong>Introduction: </strong>Infectious diseases, including invasive pneumococcal disease (IPD) and community‑acquired pneumonia (CAP), are associated with severe burden and adverse outcomes beyond the acute episode. The comprehensive burden has not been previously assessed in Finland. Here, we characterized adult patients (≥ 18 years) with IPD and CAP in Finland, followed them up for adverse outcomes, and estimated the economic burden.</p><p><strong>Methods: </strong>This is a nationwide registry-based cohort study, including 2894 adults with laboratory-confirmed IPD; 129,203 adults with inpatient CAP; 126,314 adults with outpatient CAP; and their 760,748 age-sex-region-matched controls.</p><p><strong>Results: </strong>Overall, 40-60% of the patients had at least one predefined medical risk factor; however, a substantial proportion (34-40%) of patients aged ≥ 65 years did not have any predefined risk factors. Patients aged ≥ 65 years with IPD and inpatient CAP had the highest rates of adverse outcomes, including recurrence, admission to institutional care, and acute myocardial infarction. IPD and CAP were associated with considerable attributable healthcare costs, including direct disease-specific costs, increased all-cause costs above them, and indirect costs due to work absenteeism. Serotypes included in the pneumococcal conjugate vaccines (PCVs) PCV13, PCV20, and PCV21 covered 43.0%, 61.1%, and 77.7% of IPD cases, respectively, in the age group ≥ 65 years in 2023-2024.</p><p><strong>Conclusions: </strong>IPD and CAP are associated with substantial morbidity, mortality, and economic burden, particularly among adults aged ≥ 65 years. In this age group, pneumococcal disease alone accounted for ~€39 million annually in total costs (inflated to 2023 values). As many older patients had no predefined medical risk factors, age‑based pneumococcal vaccination and broader use of higher‑valency conjugate vaccines seem warranted to reduce disease burden and societal costs.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1869-1891"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13279831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959966","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":"Outcomes and Adverse Events Among Patients with Vancomycin-Resistant Enterococcal Bloodstream Infection Treated with Daptomycin Doses Greater than 12 mg/kg.","authors":"Luo-Wei Lin, Yu-Chung Chuang, Jia-Ling Yang, Chi-Ying Lin, Sung-Hsi Huang, Jann-Tay Wang, Yee-Chun Chen, Shan-Chwen Chang","doi":"10.1007/s40121-026-01369-6","DOIUrl":"10.1007/s40121-026-01369-6","url":null,"abstract":"<p><strong>Introduction: </strong>Daptomycin is commonly used for vancomycin-resistant enterococcal bloodstream infections (VRE-BSIs); however, its optimal dosing remains uncertain. Although doses > 12 mg/kg may improve attainment of pharmacodynamic targets, clinical outcomes and safety data for very-high-dose daptomycin are limited.</p><p><strong>Methods: </strong>This multicenter cohort study included adults with a VRE-BSI treated with daptomycin doses > 12 mg/kg, between 2011 and 2024. The primary outcome was 28-day all-cause mortality. Daptomycin-associated adverse events, including creatine kinase (CK) elevation, were assessed, and multivariable logistic regression models were used to identify factors associated with mortality and an elevated CK level.</p><p><strong>Results: </strong>Among 101 patients, the median age was 70.2 years, and 67.3% had an underlying malignancy. The 28-day mortality was 41.6% and was primarily associated with host factors and illness severity. Daptomycin dose was not associated with mortality when modeled as a continuous variable; however, in exploratory post hoc analysis, doses > 13 mg/kg were associated with lower mortality compared with 12-13 mg/kg [adjusted odds ratio (aOR), 0.22; 95% confidence interval (CI) 0.05-0.98; p = 0.047]. CK elevation occurred in 13.9% and was independently associated with higher daptomycin dose (aOR, 2.99; 95% CI 1.05-8.50). Eosinophilic pneumonia was identified in 10.9% of patients.</p><p><strong>Conclusions: </strong>In patients with VRE-BSI treated with daptomycin doses > 12 mg/kg, mortality remained high and was primarily driven by host factors and severity of illness. Although exploratory findings suggest a potential mortality benefit at doses > 13 mg/kg, this must be balanced against a significantly increased risk of dose-related toxicity, including a notably high incidence of eosinophilic pneumonia.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1925-1937"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987169","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":"Micafungin Sequestration and Late Release During Continuous Renal Replacement Therapy with Polyacrylonitrile- and Polysulfone-Derived Filters.","authors":"Julien Massol, Valentin Maulet, Vincent Jullien, Solange Corriol-Rohou, Jean-Herlé Raphalen, Frédéric J Baud, Lionel Lamhaut, Olivier Lortholary","doi":"10.1007/s40121-026-01367-8","DOIUrl":"10.1007/s40121-026-01367-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Adsorption within continuous renal replacement therapy (CRRT) circuits may reduce exposure to echinocandins. Because micafungin is highly protein bound, the behavior of its unbound fraction during CRRT remains difficult to characterize. We assessed unbound micafungin disappearance from a central compartment and late release/desorption in a protein-free in vitro CRRT model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Micafungin stability was assessed in a 5-L bag of Hemosol™ B0 over 8 h. In the NeckEpur model, a 5-L protein-free central compartment was circulated at 200 mL/min for 6 h through either a polyacrylonitrile hemofilter (ST™150; post-dilution continuous veno-venous hemofiltration [CVVH], 2.5 L/h) or a polysulfone hemofilter (AV™1000). For AV™1000, one run used CVVH (2.5 L/h) and one used continuous veno-venous hemodiafiltration (CVVHDF; dialysis 1.5 L/h plus filtration 1.0 L/h). Initial micafungin concentrations in the central compartment were 2.18 mg/L or approximately 6.8 mg/L. Concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a lower limit of quantification (LLOQ) of 0.1 mg/L. Apparent central-compartment clearance (Cl_CC), sieving coefficient (Sc), and extraction coefficient (EC) were used to describe disappearance from the circuit, filtration, and late release. Sensitivity analyses replaced values &lt; LLOQ by LLOQ/2 or LLOQ/√2. Segmental sampling and within-filter mass balance were used descriptively to localize loss within the extracorporeal system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Micafungin was stable in Hemosol™ B0 over 8 h (- 5.2 ± 0.5%). With ST™150 at 2.18 mg/L, C_CC reached the LLOQ by 200 min and was below the LLOQ thereafter; apparent Cl_CC was approximately 6 L/h, effluent concentrations were not measurable, and limited late release was estimated over 120-200 min. With ST™150 at approximately 6.8 mg/L, elimination from the central compartment was 92 ± 4% at 6 h (apparent Cl_CC 4.9 ± 0.2 L/h), with within-filter contributions from measurable effluent removal (54 ± 6%) and non-effluent loss (46 ± 6%); small late release was compatible with negative EC values during 180-360 min. For AV™1000, two exploratory runs-one CVVH and one CVVHDF-showed rapid disappearance from the central compartment, with C_CC below the LLOQ by 120 min, no measurable effluent concentrations, and no negative EC values. Sensitivity analyses for values &lt; LLOQ changed the numerical Cl_CC estimates but not the overall pattern. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In this exploratory protein-free in vitro model, unbound micafungin rapidly disappeared from the CRRT circuit with both tested filter systems. ST™150 showed measurable effluent removal at higher concentrations and limited late release, whereas both exploratory AV™1","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1995-2008"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13279833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156288","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":"Prior SGLT2 Inhibitor and Metformin Use and Risk of Long COVID in Type 2 Diabetes: A Nationwide Population-Based Cohort Study.","authors":"Jinghao Nicholas Ngiam, Enoch Xueheng Loy, Matthew Chung Yi Koh, Calvin J Chiew, Russell Jingxian Li, Su Chi Lim, E Shyong Tai, Yong Mong Bee, Wai Leng Chow, David Chien Boon Lye, Yew Woon Chia, Mark Yan Yee Chan, Derek J Hausenloy, Kelvin Bryan Tan, Liang En Wee","doi":"10.1007/s40121-026-01362-z","DOIUrl":"10.1007/s40121-026-01362-z","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with type 2 diabetes mellitus (T2DM) are at increased risk of post-acute sequelae after COVID-19 (PASC). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and metformin may have systemic benefits beyond glycemic control. We evaluated the impact of prior SGLT2i and metformin use on the risk of post-acute COVID-19 complications.</p><p><strong>Methods: </strong>We conducted a retrospective, population-based cohort study using national healthcare claims databases, from July 1, 2021 to February 28, 2023. Cohorts were stratified based on SGLT2i or metformin, against patients had not received these medications. Overlap weighting was applied to adjust for baseline differences in demographics, vaccination status, comorbidities, and prior healthcare utilization. Competing-risks regression models were used to assess differences in the risk of long-COVID outcomes between 31 and 300 days post-infection.</p><p><strong>Results: </strong>Among 71,698 patients with T2DM, 22,501 (31.4%) had prior SGLT2i use, and 66,792 (93.1%) had prior metformin use. Compared with non-SGLT2i users, patients treated with SGLT2i had a significantly lower risk of neurological sequelae (aHR = 0.60 [0.45-0.81]), particularly memory and cognitive impairment (aHR = 0.63 [0.41-0.98]). SGLT2i was also associated with a reduced risk of post-acute symptoms (aHR = 0.87 [0.77-0.99]). Metformin use was associated with significantly lower risk of composite post-acute outcomes (aHR = 0.80 [0.68-0.96]) and post-acute symptoms (aHR = 0.77 [0.63-0.93]). Amongst patients on metformin, the addition of SGLT2i further lowered the risk of neurological sequelae (aHR = 0.81 [0.71-0.93]) and composite symptoms (aHR 0.87 [0.76-0.99]).</p><p><strong>Conclusion: </strong>SGLT2i and metformin use were associated with a lower risk of PASC and post-acute symptoms. There may be additional protective benefits when both agents are used concurrently.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"1955-1976"},"PeriodicalIF":5.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156331","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}