Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106645
Shumeng Han , Yiwen Liu , Baodi Xing , Yucheng Yang , Zijun Liu , Yixuan Li , Xuechen Wang , Jie Yu , Fan Ping , Wei Li , Lingling Xu , Tao Qi , Yuelun Zhang , Yuxiu Li , Huabing Zhang
Objective
To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs).
Methods
Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool.
Results
A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86–0.93; absolute risk difference, −30 per 10,000 persons/year; I² = 0%), non-serious (RR, 0.90; 95% CI, 0.85–0.97; I² = 77%), and total infections (RR, 0.89; 95% CI, 0.84–0.94; I² = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79–0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68–0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65–0.97), vascular (RR, 0.65; 95% CI, 0.47–0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72–0.92), all with I² = 0%. Meta-regression showed greater weight loss (β = −0.011; P =.045), hemoglobin A1c reduction (β = –0.229; P =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83–0.92) were associated with lower risk.
Conclusion
GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control.
{"title":"Association of glucagon-like peptide-1 receptor agonist use with risk of infections: A systematic review and meta-analysis","authors":"Shumeng Han , Yiwen Liu , Baodi Xing , Yucheng Yang , Zijun Liu , Yixuan Li , Xuechen Wang , Jie Yu , Fan Ping , Wei Li , Lingling Xu , Tao Qi , Yuelun Zhang , Yuxiu Li , Huabing Zhang","doi":"10.1016/j.jinf.2025.106645","DOIUrl":"10.1016/j.jinf.2025.106645","url":null,"abstract":"<div><h3>Objective</h3><div>To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs).</div></div><div><h3>Methods</h3><div>Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool.</div></div><div><h3>Results</h3><div>A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86–0.93; absolute risk difference, −30 per 10,000 persons/year; <em>I²</em> = 0%), non-serious (RR, 0.90; 95% CI, 0.85–0.97; <em>I²</em> = 77%), and total infections (RR, 0.89; 95% CI, 0.84–0.94; <em>I²</em> = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79–0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68–0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65–0.97), vascular (RR, 0.65; 95% CI, 0.47–0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72–0.92), all with <em>I²</em> = 0%. Meta-regression showed greater weight loss (β = −0.011; <em>P</em> =.045), hemoglobin A1c reduction (β = –0.229; <em>P</em> =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83–0.92) were associated with lower risk.</div></div><div><h3>Conclusion</h3><div>GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106645"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106647
Gábor Endre Tóth , Marike Petersen , Francois Chevenet , Marcy Sikora , Alexandru Tomazatos , Alexandra Bialonski , Heike Baum , Balázs Horváth , Padet Siriyasatien , Anna Heitmann , Stephanie Jansen , Ruth Offergeld , Raskit Lachmann , Michael Schmidt , Jonas Schmidt-Chanasit , Dániel Cadar
Background
West Nile virus (WNV) has emerged as a public health concern in Germany since its first detection in 2018, with evidence of expanding geographic spread. Genomic surveillance is critical for tracking viral evolution, identifying introductions, and monitoring local transmission. However, genome recovery from low-viremia samples such as those obtained through blood donor screening remains technically challenging.
Aim
To develop and validate a sensitive amplicon-based sequencing protocol optimized for WNV lineage 2 and apply it to low-titer samples to support genomic surveillance in Germany.
Methods
A novel primer scheme was designed for WNV lineage 2 and applied to 43 nucleic acid testing (NAT)-positive blood donor samples collected between 2020 and 2024. Amplicon-based sequencing performance was benchmarked against metagenomic next-generation sequencing (mNGS). Recovered genomes were subjected to phylogenomic analysis to assess viral diversity and transmission dynamics.
Results
The amplicon protocol enabled genome recovery (>70% coverage) from samples with viral loads as low as ∼10¹ RNA copies/µL, outperforming metagenomic NGS (mNGS). Of the 43 samples, 30 yielded complete or near-complete genomes. Six distinct WNV subclades (2A–2F), including German strains, were identified, indicating multiple introductions into Germany from Central Europe. Subclade 2F emerged as the dominant and widely distributed group. Berlin, Brandenburg, Saxony, and Saxony-Anhalt were identified as persistent transmission hubs.
Conclusion
This study highlights blood donors as valuable sentinels for WNV genomic surveillance. The validated amplicon-based sequencing approach enables sensitive, scalable genome recovery from low-viremia samples, and when integrated with routine blood donor screening, provides a robust framework for early detection, transmission dynamics, and public health preparedness.
{"title":"Blood donors as sentinels for genomic surveillance of West Nile virus in Germany using a sensitive amplicon-based sequencing approach","authors":"Gábor Endre Tóth , Marike Petersen , Francois Chevenet , Marcy Sikora , Alexandru Tomazatos , Alexandra Bialonski , Heike Baum , Balázs Horváth , Padet Siriyasatien , Anna Heitmann , Stephanie Jansen , Ruth Offergeld , Raskit Lachmann , Michael Schmidt , Jonas Schmidt-Chanasit , Dániel Cadar","doi":"10.1016/j.jinf.2025.106647","DOIUrl":"10.1016/j.jinf.2025.106647","url":null,"abstract":"<div><h3>Background</h3><div>West Nile virus (WNV) has emerged as a public health concern in Germany since its first detection in 2018, with evidence of expanding geographic spread. Genomic surveillance is critical for tracking viral evolution, identifying introductions, and monitoring local transmission. However, genome recovery from low-viremia samples such as those obtained through blood donor screening remains technically challenging.</div></div><div><h3>Aim</h3><div>To develop and validate a sensitive amplicon-based sequencing protocol optimized for WNV lineage 2 and apply it to low-titer samples to support genomic surveillance in Germany.</div></div><div><h3>Methods</h3><div>A novel primer scheme was designed for WNV lineage 2 and applied to 43 nucleic acid testing (NAT)-positive blood donor samples collected between 2020 and 2024. Amplicon-based sequencing performance was benchmarked against metagenomic next-generation sequencing (mNGS). Recovered genomes were subjected to phylogenomic analysis to assess viral diversity and transmission dynamics.</div></div><div><h3>Results</h3><div>The amplicon protocol enabled genome recovery (>70% coverage) from samples with viral loads as low as ∼10¹ RNA copies/µL, outperforming metagenomic NGS (mNGS). Of the 43 samples, 30 yielded complete or near-complete genomes. Six distinct WNV subclades (2A–2F), including German strains, were identified, indicating multiple introductions into Germany from Central Europe. Subclade 2F emerged as the dominant and widely distributed group. Berlin, Brandenburg, Saxony, and Saxony-Anhalt were identified as persistent transmission hubs.</div></div><div><h3>Conclusion</h3><div>This study highlights blood donors as valuable sentinels for WNV genomic surveillance. The validated amplicon-based sequencing approach enables sensitive, scalable genome recovery from low-viremia samples, and when integrated with routine blood donor screening, provides a robust framework for early detection, transmission dynamics, and public health preparedness.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106647"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106643
David B. Meya , Manu De Rycker , Ian H. Gilbert , William Hope , Justine Jelagat Odionyi , Michael Keegan , Angela Loyse , Pablo Moral-Lopez , Peter R. Williamson , Lionel K. Tan , Isabela Ribeiro , Timothy J. Miles
Cryptococcus neoformans and Cryptococcus gattii are World Health Organization critical and medium priority pathogens, respectively. These mainly impact people with human immunodeficiency virus residing in low- and middle-income countries, but other patient groups and settings are also affected. The high global morbidity and mortality and the limitations of current treatments provided an impetus for the development of a target product profile (TPP) for new anti-cryptococcal agents. Key attributes of the TPP include improved safety, superior (or at least comparable) activity to current treatments against all syndromes across the full disease spectrum (cryptococcal meningitis, cryptococcal pneumonia, etc.), relevance for C. neoformans and C. gattii, suitability for all age groups, oral and intravenous formulations, an acceptable treatment regimen, minimal/manageable drug-drug interactions, thermostability, and a barrier to resistance at least as high as current options. The aim of this TPP, along with the suggested discovery and development paths, is to assist all stakeholders in the development of novel cryptococcal disease treatments.
{"title":"Target product profile and discovery and development path for novel cryptococcal disease treatments","authors":"David B. Meya , Manu De Rycker , Ian H. Gilbert , William Hope , Justine Jelagat Odionyi , Michael Keegan , Angela Loyse , Pablo Moral-Lopez , Peter R. Williamson , Lionel K. Tan , Isabela Ribeiro , Timothy J. Miles","doi":"10.1016/j.jinf.2025.106643","DOIUrl":"10.1016/j.jinf.2025.106643","url":null,"abstract":"<div><div><em>Cryptococcus neoformans</em> and <em>Cryptococcus gattii</em> are World Health Organization critical and medium priority pathogens, respectively. These mainly impact people with human immunodeficiency virus residing in low- and middle-income countries, but other patient groups and settings are also affected. The high global morbidity and mortality and the limitations of current treatments provided an impetus for the development of a target product profile (TPP) for new anti-cryptococcal agents. Key attributes of the TPP include improved safety, superior (or at least comparable) activity to current treatments against all syndromes across the full disease spectrum (cryptococcal meningitis, cryptococcal pneumonia, etc.), relevance for <em>C. neoformans</em> and <em>C. gattii</em>, suitability for all age groups, oral and intravenous formulations, an acceptable treatment regimen, minimal/manageable drug-drug interactions, thermostability, and a barrier to resistance at least as high as current options. The aim of this TPP, along with the suggested discovery and development paths, is to assist all stakeholders in the development of novel cryptococcal disease treatments.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106643"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106636
Sabina Andreu , Daniel Galdo-Torres , Inés Ripa , Oliver Caballero , Raquel Bello-Morales , José Antonio López-Guerrero
Genital herpes (GH), historically associated with herpes simplex virus type 2 (HSV-2), is changing its etiology. Since the last few decades, there has been an increase in genital infections caused by herpes simplex virus type 1 (HSV-1). In fact, in several countries, preferably in high-income regions such as North America or Western Europe, HSV-1 has become the leading cause of first-episode GH, especially among adolescents and young adults. However, the epidemiological trend varies geographically, with slower changes observed in Africa, Latin America, and Southeast Asia, where GH HSV-2 remains dominant. This epidemiological shift may be mainly due to the decline in HSV-1 seroprevalence, decreased childhood exposure to the virus, and changes in sexual practices. Despite the global decline in HSV-1 seroprevalence, GH caused by HSV-1 is rising by 1–2% annually in many areas. This review summarizes the seroprevalence of HSV-1/-2 worldwide in recent decades and discusses the changes in GH etiology and contributing factors. Despite the substantial global burden of the disease and its psychosocial impact, no vaccine or curative treatment exists. Active surveillance, health and sexual health education, and targeted interventions are vital to manage this changing landscape and to mitigate the public health issue posed by GH and HSV-1.
{"title":"From HSV-2 to HSV-1: A change in the epidemiology of genital herpes","authors":"Sabina Andreu , Daniel Galdo-Torres , Inés Ripa , Oliver Caballero , Raquel Bello-Morales , José Antonio López-Guerrero","doi":"10.1016/j.jinf.2025.106636","DOIUrl":"10.1016/j.jinf.2025.106636","url":null,"abstract":"<div><div>Genital herpes (GH), historically associated with herpes simplex virus type 2 (HSV-2), is changing its etiology. Since the last few decades, there has been an increase in genital infections caused by herpes simplex virus type 1 (HSV-1). In fact, in several countries, preferably in high-income regions such as North America or Western Europe, HSV-1 has become the leading cause of first-episode GH, especially among adolescents and young adults. However, the epidemiological trend varies geographically, with slower changes observed in Africa, Latin America, and Southeast Asia, where GH HSV-2 remains dominant. This epidemiological shift may be mainly due to the decline in HSV-1 seroprevalence, decreased childhood exposure to the virus, and changes in sexual practices. Despite the global decline in HSV-1 seroprevalence, GH caused by HSV-1 is rising by 1–2% annually in many areas. This review summarizes the seroprevalence of HSV-1/-2 worldwide in recent decades and discusses the changes in GH etiology and contributing factors. Despite the substantial global burden of the disease and its psychosocial impact, no vaccine or curative treatment exists. Active surveillance, health and sexual health education, and targeted interventions are vital to manage this changing landscape and to mitigate the public health issue posed by GH and HSV-1.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106636"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106644
L. Østergaard , A. Dahl , S. Chamat-Hedemand , A. Stahl , M.M. Pries-Heje , C. Moser , K.K. Søgaard , C.N. Agergaard , K.K. Mortensen , K. Iversen , H. Bundgaard , M. Voldstedlund , L. Køber , N.E. Bruun , E.L. Fosbøl
Background
Some studies have suggested an association between Enterococcus faecalis blood stream infection (BSI) and colorectal cancer (CRC) suggesting that screening for CRC could be reasonable. However, these studies were limited by small numbers with low generalizability.
Methods
Danish nationwide registries were used to identify patients with first-time E. faecalis BSI from 2010 to 2021 without previous colorectal neoplasia (CRN). Age-, sex- and calendar-matched comparators from the general population were identified (1:5). We estimated the six-month cumulative incidence of CRC and CRN and a multivariable adjusted Cox analysis was used for relative comparison between groups.
Results
We identified 4664 patients with E. faecalis BSI (median age: 74.9 years, 73.4% males) and 23,320 comparators from the general population. For patients with E. faecalis BSI the six-month incidence of CRC was 0.45% (95% CI: 0.28–0.72%) and of CRN 2.34% (95% CI: 1.88–2.88). For matched comparators the incidence of CRC was 0.12% (95% CI: 0.08–0.17) and of CRN 0.48% (95% CI: 0.39–0.57). In adjusted analysis, patients with E. faecalis BSI had a higher HR of CRC (HR=3.70 (95% CI: 1.91–7.19) and CRN (HR=4.64 (95% CI: 3.40–6.34) than matched comparators. The six-month mortality was 36.3% in patients with E. faecalis BSI while this was 1.7% among comparators.
Conclusion
In patients with first-time E. faecalis BSI the six months incidence of CRC was around 0.5% and 2.3% for the diagnosis of CRN, which were 3–4 times higher than in a matched cohort from the general population. Nevertheless, the absolute risks do not justify systematic screening for CRC or CRN in patients with E. faecalis BSI.
{"title":"Prevalence of colorectal cancer in patients with Enterococcus faecalis blood stream infection: A nationwide study","authors":"L. Østergaard , A. Dahl , S. Chamat-Hedemand , A. Stahl , M.M. Pries-Heje , C. Moser , K.K. Søgaard , C.N. Agergaard , K.K. Mortensen , K. Iversen , H. Bundgaard , M. Voldstedlund , L. Køber , N.E. Bruun , E.L. Fosbøl","doi":"10.1016/j.jinf.2025.106644","DOIUrl":"10.1016/j.jinf.2025.106644","url":null,"abstract":"<div><h3>Background</h3><div>Some studies have suggested an association between <em>Enterococcus faecalis</em> blood stream infection (BSI) and colorectal cancer (CRC) suggesting that screening for CRC could be reasonable. However, these studies were limited by small numbers with low generalizability.</div></div><div><h3>Methods</h3><div>Danish nationwide registries were used to identify patients with first-time <em>E. faecalis</em> BSI from 2010 to 2021 without previous colorectal neoplasia (CRN). Age-, sex- and calendar-matched comparators from the general population were identified (1:5). We estimated the six-month cumulative incidence of CRC and CRN and a multivariable adjusted Cox analysis was used for relative comparison between groups.</div></div><div><h3>Results</h3><div>We identified 4664 patients with <em>E. faecalis</em> BSI (median age: 74.9 years, 73.4% males) and 23,320 comparators from the general population. For patients with <em>E. faecalis</em> BSI the six-month incidence of CRC was 0.45% (95% CI: 0.28–0.72%) and of CRN 2.34% (95% CI: 1.88–2.88). For matched comparators the incidence of CRC was 0.12% (95% CI: 0.08–0.17) and of CRN 0.48% (95% CI: 0.39–0.57). In adjusted analysis, patients with <em>E. faecalis</em> BSI had a higher HR of CRC (HR=3.70 (95% CI: 1.91–7.19) and CRN (HR=4.64 (95% CI: 3.40–6.34) than matched comparators. The six-month mortality was 36.3% in patients with E. faecalis BSI while this was 1.7% among comparators.</div></div><div><h3>Conclusion</h3><div>In patients with first-time <em>E. faecalis</em> BSI the six months incidence of CRC was around 0.5% and 2.3% for the diagnosis of CRN, which were 3–4 times higher than in a matched cohort from the general population. Nevertheless, the absolute risks do not justify systematic screening for CRC or CRN in patients with <em>E. faecalis</em> BSI.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106644"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106629
Sarah Sedik , Matthias Egger , Stella Wolfgruber , Jon Salmanton-García , Matteo Bassetti , Malgorzata Mikulska , Volkan Özenci , Sevtap Arikan-Akdagli , Murat Akova , Jean-Pierre Gangneux , Alessandra Bandera , Ana Alastruey-Izquierdo , Aleksandra Barac , Riina Rautemaa-Richardson , Nick A. de Jonge , Laura Loughlin , Ola Blennow , Fanny Lanternier , Eelco F.J. Meijer , Nina Khanna , Martin Hoenigl
Objectives
Candidemia is a severe complication in critically ill and immunocompromised patients, and is associated with high morbidity and mortality. While early fungal clearance may improve outcomes, the association between follow-up blood culture (FUBCs) results and clinical outcomes remains insufficiently explored. This sub-analysis of the ECMM Candida III study investigates predictors of persistent candidemia and the impact of positive FUBC results on clinical outcomes.
Methods
The multicenter ECMM Candida III study enrolled adults with culture-proven candidemia from 60 European centers (2018–2019). This sub-analysis included patients with at least one FUBC result reported (n = 258; 40.8%). Statistical analysis used SPSS 29 and R. Binary logistic regression was used to identify predictors of persistent candidemia. To assess mortality risk factors, Cox proportional hazards regression models were constructed.
Results
Of 258 patients, 52 (20.2%) had persistent candidemia based on positive FUBCs (median duration of candidemia 6 days). Utilization of echinocandins as first line treatment was less frequent (61.5% vs. 78.2%; p=0.014) in those with positive FUBCs. Mortality was significantly higher in the FUBC-positive group (50% vs. 32%; p=0.016). In the multivariable logistic regression model, lower EQUAL Candida Scores, reflecting reduced adherence to guideline-recommended management, were independently associated with persistent candidemia (OR 0.003, 95% CI 0.0002–0.07; p<0.001). Univariable Cox regression identified persistent candidemia ≥5 days (HR 2.16; 95% CI 1.33–3.53; p= 0.002) as a significant predictor of mortality. In the multivariable Cox regression model, intensive care unit (ICU) admission (HR 1.59, 95% CI 1.02–2.50; p= 0.039) and persistent candidemia ≥5 days (HR 2.06, 95% CI 1.26–3.37; p= 0.004) remained independent predictors of mortality.
Conclusion
Persistent candidemia was predicted by poor adherence to treatment guidelines, as shown by low EQUAL Candida Scores, particularly due to the lack of initial echinocandin use. After controlling immortal time bias, persistent candidemia ≥5 days and ICU admission remained independent predictors of mortality in the multivariable model.
目的：念珠菌病是危重症和免疫功能低下患者的严重并发症，具有高发病率和高死亡率。虽然早期真菌清除可能改善预后，但随访血培养（fubc）结果与临床结果之间的关系仍未得到充分探讨。ECMM念珠菌III研究的亚分析研究了持续性念珠菌的预测因素以及FUBC阳性结果对临床结果的影响。方法：多中心ECMM念珠菌III研究招募了来自欧洲60个中心（2018-2019）的培养证实念珠菌病的成人。该亚组分析包括至少有一个报告的FUBC结果的患者（n = 258; 40.8%）。采用SPSS 29和SPSS r进行统计学分析。采用二元logistic回归确定持续性念珠菌的预测因素。为评估死亡危险因素，构建Cox比例风险回归模型。结果：258例患者中，52例（20.2%）存在基于fubc阳性的持续性念珠菌病（念珠菌病中位持续时间6天）。在fubc阳性的患者中，使用棘白菌素作为一线治疗的频率较低（61.5%比78.2%;p=0.014）。fubc阳性组的死亡率显著高于对照组（50% vs. 32%; p=0.016）。在多变量logistic回归模型中，较低的EQUAL念珠菌评分，反映了对指南推荐管理的依从性降低，与持续性念珠菌血症独立相关（OR 0.003, 95% CI 0.0002 - 0.07）。结论：持续性念珠菌血症的预测与对治疗指南的依从性较差有关，如较低的EQUAL念珠菌评分所示，特别是由于缺乏初始使用棘白菌素。在控制存活时间偏差后，在多变量模型中，持续念珠菌≥5天和入住ICU仍然是死亡率的独立预测因子。资金来源：研究者发起的研究基金从Scynexis和Mundipharma获得，以支持该研究。
{"title":"Risk factors for persistent candidemia and prognostic implications: Results from the ECMM Candida III study","authors":"Sarah Sedik , Matthias Egger , Stella Wolfgruber , Jon Salmanton-García , Matteo Bassetti , Malgorzata Mikulska , Volkan Özenci , Sevtap Arikan-Akdagli , Murat Akova , Jean-Pierre Gangneux , Alessandra Bandera , Ana Alastruey-Izquierdo , Aleksandra Barac , Riina Rautemaa-Richardson , Nick A. de Jonge , Laura Loughlin , Ola Blennow , Fanny Lanternier , Eelco F.J. Meijer , Nina Khanna , Martin Hoenigl","doi":"10.1016/j.jinf.2025.106629","DOIUrl":"10.1016/j.jinf.2025.106629","url":null,"abstract":"<div><h3>Objectives</h3><div>Candidemia is a severe complication in critically ill and immunocompromised patients, and is associated with high morbidity and mortality. While early fungal clearance may improve outcomes, the association between follow-up blood culture (FUBCs) results and clinical outcomes remains insufficiently explored. This sub-analysis of the ECMM <em>Candida</em> III study investigates predictors of persistent candidemia and the impact of positive FUBC results on clinical outcomes.</div></div><div><h3>Methods</h3><div>The multicenter ECMM <em>Candida</em> III study enrolled adults with culture-proven candidemia from 60 European centers (2018–2019). This sub-analysis included patients with at least one FUBC result reported (n = 258; 40.8%). Statistical analysis used SPSS 29 and R. Binary logistic regression was used to identify predictors of persistent candidemia. To assess mortality risk factors, Cox proportional hazards regression models were constructed.</div></div><div><h3>Results</h3><div>Of 258 patients, 52 (20.2%) had persistent candidemia based on positive FUBCs (median duration of candidemia 6 days). Utilization of echinocandins as first line treatment was less frequent (61.5% vs. 78.2%; p=0.014) in those with positive FUBCs. Mortality was significantly higher in the FUBC-positive group (50% vs. 32%; p=0.016). In the multivariable logistic regression model, lower EQUAL <em>Candida</em> Scores, reflecting reduced adherence to guideline-recommended management, were independently associated with persistent candidemia (OR 0.003, 95% CI 0.0002–0.07; p<0.001). Univariable Cox regression identified persistent candidemia ≥5 days (HR 2.16; 95% CI 1.33–3.53; p= 0.002) as a significant predictor of mortality. In the multivariable Cox regression model, intensive care unit (ICU) admission (HR 1.59, 95% CI 1.02–2.50; p= 0.039) and persistent candidemia ≥5 days (HR 2.06, 95% CI 1.26–3.37; p= 0.004) remained independent predictors of mortality.</div></div><div><h3>Conclusion</h3><div>Persistent candidemia was predicted by poor adherence to treatment guidelines, as shown by low EQUAL <em>Candida</em> Scores, particularly due to the lack of initial echinocandin use. After controlling immortal time bias, persistent candidemia ≥5 days and ICU admission remained independent predictors of mortality in the multivariable model.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106629"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106651
Juan Ambrosioni , Elisa de Lazzari , Sonsoles Sánchez-Palomino , Lucía Bailón , Paula Suanzes , Carmen Busca , Luis Ramos-Ruperto , Eva Orviz , Ángel Rivero , Beatriz Mothe , Jorge Del Romero , Vicenç Falcó , Sònia Vicens-Artés , Elisa Moraga , Anna Cruceta , Josep Mallolas , Josep M. Miró , the BIC-PHI Study Group
Objectives
We evaluated the efficacy, safety and impact on viral reservoir of rapid bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) initiation during primary HIV infection (PHI).
Methods
Multicenter, single-arm clinical trial in participants with PHI of <3 months (seroconversion or incomplete serological pattern), starting BIC/FTC/TAF in 6 Spanish centers between January-2021 and September-2022. Primary endpoint was proportion of participants with viral load (VL)<50 copies/mL at 48-weeks on the Intention-to-treat-exposed population (ITTe). Cases were compared with randomly-matched retrospective PHI controls, starting other 3-drug Integrase-Strand-Transfer-inhibitor-based regimens. Reservoir was evaluated in PHI cases by Intact Proviral DNA Assay (IPDA).
Results
We included 64 participants, 94% cis-male, aged 32 (26;41) years.; 78% men-who-have-sex-with-men. At BIC/FTC/TAF initiation, Fiebig stages were II (14%), III (11%); IV (5%), V (54%) and VI (16%); VL was 496,520 (110,000;1,285,000) copies/mL; 62% were subtype B; median (IQR) CD4 T cell count was 406 (322;535) cells/µL; 6% had active hepatitis B virus co-infection. All participants started BIC/FTC/TAF at first specialist consultation. 81% (ITTe) and 93% (On-Treatment, OT) had VL<50 copies/mL at 48-weeks. 72% had adverse events, only 3% were grade 3/4; 91% were not-related, none led to BIC/FTC/TAF-discontinuation. 92% of controls (OT) had VL<50 copies/mL at 48-weeks (p=0.914), 11% (17%) modified initial antiretroviral regimen (p>0.001). Intact and defective proviral DNA levels significantly decreased at 48-weeks.
Conclusions
BIC/FTC/TAF showed rapid viral decay, high suppression rates, good tolerability, and reservoir decline in PHI, making it an appealing regimen in this setting.
{"title":"Bictegravir/emtricitabine/tenofovir alafenamide for primary HIV infection: Efficacy, safety and impact on viral reservoir (the BIC-PHI clinical trial)","authors":"Juan Ambrosioni , Elisa de Lazzari , Sonsoles Sánchez-Palomino , Lucía Bailón , Paula Suanzes , Carmen Busca , Luis Ramos-Ruperto , Eva Orviz , Ángel Rivero , Beatriz Mothe , Jorge Del Romero , Vicenç Falcó , Sònia Vicens-Artés , Elisa Moraga , Anna Cruceta , Josep Mallolas , Josep M. Miró , the BIC-PHI Study Group","doi":"10.1016/j.jinf.2025.106651","DOIUrl":"10.1016/j.jinf.2025.106651","url":null,"abstract":"<div><h3>Objectives</h3><div>We evaluated the efficacy, safety and impact on viral reservoir of rapid bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) initiation during primary HIV infection (PHI).</div></div><div><h3>Methods</h3><div>Multicenter, single-arm clinical trial in participants with PHI of <3 months (seroconversion or incomplete serological pattern), starting BIC/FTC/TAF in 6 Spanish centers between January-2021 and September-2022. Primary endpoint was proportion of participants with viral load (VL)<50 copies/mL at 48-weeks on the Intention-to-treat-exposed population (ITTe). Cases were compared with randomly-matched retrospective PHI controls, starting other 3-drug Integrase-Strand-Transfer-inhibitor-based regimens. Reservoir was evaluated in PHI cases by Intact Proviral DNA Assay (IPDA).</div></div><div><h3>Results</h3><div>We included 64 participants, 94% cis-male, aged 32 (26;41) years.; 78% men-who-have-sex-with-men. At BIC/FTC/TAF initiation, Fiebig stages were II (14%), III (11%); IV (5%), V (54%) and VI (16%); VL was 496,520 (110,000;1,285,000) copies/mL; 62% were subtype B; median (IQR) CD4 T cell count was 406 (322;535) cells/µL; 6% had active hepatitis B virus co-infection. All participants started BIC/FTC/TAF at first specialist consultation. 81% (ITTe) and 93% (On-Treatment, OT) had VL<50 copies/mL at 48-weeks. 72% had adverse events, only 3% were grade 3/4; 91% were not-related, none led to BIC/FTC/TAF-discontinuation. 92% of controls (OT) had VL<50 copies/mL at 48-weeks (p=0.914), 11% (17%) modified initial antiretroviral regimen (p>0.001). Intact and defective proviral DNA levels significantly decreased at 48-weeks.</div></div><div><h3>Conclusions</h3><div>BIC/FTC/TAF showed rapid viral decay, high suppression rates, good tolerability, and reservoir decline in PHI, making it an appealing regimen in this setting.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106651"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.jinf.2025.106635
Ray Borrow , Dominque A. Caugant , Stephen A. Clark , Ener Çagri Dinleyici , Ian Hall , Lee H. Harrison , William P. Hausdorff , Shamez N. Ladhani , Jay Lucidarme , Marco A.P. Sáfadi , Vinny Smith , Muhamed-Kheir Taha , Julio Vázquez
This review outlines recent trends on invasive meningococcal disease (IMD) discussed at the latest meeting of the Global Meningococcal Initiative (GMI). There has been a re-emergence of the Hajj strain sublineage (serogroup W; ST-11 clonal complex), with travel to the Kingdom of Saudi Arabia being a critical factor in transmission. The epidemiology of IMD has also changed following the COVID-19 pandemic, with annual IMD cases increasing in many countries. For example, the highest number of IMD cases since 2014 was reported in the USA in 2023–2024. Atypical presentations of IMD have been prominent irrespective of the pandemic. For instance, an increase in cases of meningococcal epiglottitis has been reported in France in 2022–2023 (serogroups W and Y). When considering vaccination, the GMI has identified a need for broader meningococcal serogroup B (MenB) immunisation owing to the potential impact of the vaccines on reducing IMD incidence caused by other serogroups than MenB. There is also a case for using MenB vaccination to protect against Neisseria gonorrhoeae infection based on initial evidence, albeit further studies will need to be conducted.
{"title":"Current global trends in meningococcal disease control, risk groups and vaccination: Consensus of the Global Meningococcal Initiative","authors":"Ray Borrow , Dominque A. Caugant , Stephen A. Clark , Ener Çagri Dinleyici , Ian Hall , Lee H. Harrison , William P. Hausdorff , Shamez N. Ladhani , Jay Lucidarme , Marco A.P. Sáfadi , Vinny Smith , Muhamed-Kheir Taha , Julio Vázquez","doi":"10.1016/j.jinf.2025.106635","DOIUrl":"10.1016/j.jinf.2025.106635","url":null,"abstract":"<div><div>This review outlines recent trends on invasive meningococcal disease (IMD) discussed at the latest meeting of the Global Meningococcal Initiative (GMI). There has been a re-emergence of the Hajj strain sublineage (serogroup W; ST-11 clonal complex), with travel to the Kingdom of Saudi Arabia being a critical factor in transmission. The epidemiology of IMD has also changed following the COVID-19 pandemic, with annual IMD cases increasing in many countries. For example, the highest number of IMD cases since 2014 was reported in the USA in 2023–2024. Atypical presentations of IMD have been prominent irrespective of the pandemic. For instance, an increase in cases of meningococcal epiglottitis has been reported in France in 2022–2023 (serogroups W and Y). When considering vaccination, the GMI has identified a need for broader meningococcal serogroup B (MenB) immunisation owing to the potential impact of the vaccines on reducing IMD incidence caused by other serogroups than MenB. There is also a case for using MenB vaccination to protect against <em>Neisseria gonorrhoeae</em> infection based on initial evidence, albeit further studies will need to be conducted.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106635"},"PeriodicalIF":11.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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