Journal of Infection最新文献_第2页

Rapid and accurate diagnosis of urinary tract infections using targeted next-generation sequencing: A multicenter comparative study with metagenomic sequencing and traditional culture methods

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-07 DOI: 10.1016/j.jinf.2025.106459

Zhenglin Chang , Jiwang Deng , Jinhu Zhang , Haojie Wu , Yuanyuan Wu , Lai Bin , Danmei Li , Jingxing Liu , Rixia Yu , Huaming Lin , Lingyue An , Baoqing Sun

Background

Urinary tract infections (UTIs) rank among the most prevalent bacterial infections globally. Traditional urine culture methods have significant limitations in detection time and sensitivity, prompting the need to evaluate targeted next-generation sequencing (tNGS) as a potential diagnostic tool.

Methods

The study included a discovery cohort of 400 suspected UTI patients (202 analyzed) and a validation cohort of 200 patients (110 analyzed). The study assessed detection time, concordance rates, ability to identify polymicrobial infections, and antibiotic resistance genes (ARGs). Both clear and turbid urine samples were evaluated across different clinical settings.

Results

In the discovery cohort, tNGS demonstrated 96.5% concordance with culture-positive samples, while showing superior specificity in culture-negative specimens (53.1% vs 28.1% for mNGS). Detection time for tNGS (12.89 h) was notably shorter than mNGS (17.38 h) and traditional culture (61.48 h). tNGS exhibited remarkable capability in identifying polymicrobial infections (55.4% of samples), significantly outperforming both mNGS (27.7%) and traditional culture methods, which failed to detect any co-infections. The method showed particular strength in detecting fastidious organisms like Ureaplasma parvum and fungal species such as Candida tropicalis. For antibiotic resistance prediction, tNGS detected more ARGs (52.67% vs 41.22% for mNGS) and achieved 100% sensitivity for vancomycin and methicillin resistance in Gram-positive pathogens. The validation cohort confirmed tNGS's robust performance, maintaining high concordance rates for both culture-positive (90.00%) and culture-negative samples (55.00%), demonstrating consistent reliability across different clinical settings

Conclusions

tNGS demonstrates advantages in rapid and accurate UTI diagnosis, particularly in detecting polymicrobial infections and analyzing antibiotic resistance genes. It shows promise as an effective complementary tool for UTI diagnostics.

{"title":"Rapid and accurate diagnosis of urinary tract infections using targeted next-generation sequencing: A multicenter comparative study with metagenomic sequencing and traditional culture methods","authors":"Zhenglin Chang , Jiwang Deng , Jinhu Zhang , Haojie Wu , Yuanyuan Wu , Lai Bin , Danmei Li , Jingxing Liu , Rixia Yu , Huaming Lin , Lingyue An , Baoqing Sun","doi":"10.1016/j.jinf.2025.106459","DOIUrl":"10.1016/j.jinf.2025.106459","url":null,"abstract":"<div><h3>Background</h3><div>Urinary tract infections (UTIs) rank among the most prevalent bacterial infections globally. Traditional urine culture methods have significant limitations in detection time and sensitivity, prompting the need to evaluate targeted next-generation sequencing (tNGS) as a potential diagnostic tool.</div></div><div><h3>Methods</h3><div>The study included a discovery cohort of 400 suspected UTI patients (202 analyzed) and a validation cohort of 200 patients (110 analyzed). The study assessed detection time, concordance rates, ability to identify polymicrobial infections, and antibiotic resistance genes (ARGs). Both clear and turbid urine samples were evaluated across different clinical settings.</div></div><div><h3>Results</h3><div>In the discovery cohort, tNGS demonstrated 96.5% concordance with culture-positive samples, while showing superior specificity in culture-negative specimens (53.1% vs 28.1% for mNGS). Detection time for tNGS (12.89 h) was notably shorter than mNGS (17.38 h) and traditional culture (61.48 h). tNGS exhibited remarkable capability in identifying polymicrobial infections (55.4% of samples), significantly outperforming both mNGS (27.7%) and traditional culture methods, which failed to detect any co-infections. The method showed particular strength in detecting fastidious organisms like Ureaplasma parvum and fungal species such as Candida tropicalis. For antibiotic resistance prediction, tNGS detected more ARGs (52.67% vs 41.22% for mNGS) and achieved 100% sensitivity for vancomycin and methicillin resistance in Gram-positive pathogens. The validation cohort confirmed tNGS's robust performance, maintaining high concordance rates for both culture-positive (90.00%) and culture-negative samples (55.00%), demonstrating consistent reliability across different clinical settings</div></div><div><h3>Conclusions</h3><div>tNGS demonstrates advantages in rapid and accurate UTI diagnosis, particularly in detecting polymicrobial infections and analyzing antibiotic resistance genes. It shows promise as an effective complementary tool for UTI diagnostics.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106459"},"PeriodicalIF":14.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic epidemiology and antimicrobial resistance reveal local transmission dynamics of enteric fever in Shenzhen, one of the mega cities in China

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-07 DOI: 10.1016/j.jinf.2025.106469

Yixiang Jiang , Min Jiang , Xin Lu , Meiying Yan , Xiaolu Shi , Qinghua Hu , Biao Kan

Objectives

Outbreak of enteric fever and the spread of antimicrobial-resistant Salmonella Typhi and S. Paratyphi pose significant public health challenges in low- and middle-income countries. Understanding the transmission dynamics of these pathogens is essential for developing effective control strategies.

Methods

We conducted phylogenomic analyses and integrated epidemiological data from 135 S. Typhi and 271 S. Paratyphi A isolates collected in Shenzhen from 2001 to 2017. Phylogenetic and temporal analyses were performed to identify prevalent genotypes and assess transmission patterns.

Results

Analyses of S. Typhi isolates in Shenzhen revealed high genetic diversity, with genotypes 3.2.1 (37.8%) and 2.1.7 (20%) being most prevalent. Genotype 3.2.1 formed an independent lineage due to mutations in the quinolone resistance-determining region (QRDR). The multidrug-resistant haplotype 58 (genotype 4.3.1) has been present since 2006. S. Paratyphi A isolates were predominantly genotype 2.3.3 (98.5%). Pathogen exchange occurred with at least four other provinces. A cutoff of ≤3 single nucleotide polymorphisms (SNPs) was effective for outbreak investigation, and 22 genomic clusters were found, suggesting undetected outbreaks or transmission events. While 80% of isolates were susceptible to first-line antibiotics, 16.9% of S. Paratyphi A isolates were multidrug-resistant.

Conclusions

This study provides insights into the transmission dynamics of enteric fever in Shenzhen, underscoring the need for ongoing genomic surveillance to manage and control outbreaks effectively.

{"title":"Genomic epidemiology and antimicrobial resistance reveal local transmission dynamics of enteric fever in Shenzhen, one of the mega cities in China","authors":"Yixiang Jiang , Min Jiang , Xin Lu , Meiying Yan , Xiaolu Shi , Qinghua Hu , Biao Kan","doi":"10.1016/j.jinf.2025.106469","DOIUrl":"10.1016/j.jinf.2025.106469","url":null,"abstract":"<div><h3>Objectives</h3><div>Outbreak of enteric fever and the spread of antimicrobial-resistant <em>Salmonella</em> Typhi and <em>S</em>. Paratyphi pose significant public health challenges in low- and middle-income countries. Understanding the transmission dynamics of these pathogens is essential for developing effective control strategies.</div></div><div><h3>Methods</h3><div>We conducted phylogenomic analyses and integrated epidemiological data from 135 <em>S.</em> Typhi and 271 <em>S.</em> Paratyphi A isolates collected in Shenzhen from 2001 to 2017. Phylogenetic and temporal analyses were performed to identify prevalent genotypes and assess transmission patterns.</div></div><div><h3>Results</h3><div>Analyses of <em>S.</em> Typhi isolates in Shenzhen revealed high genetic diversity, with genotypes 3.2.1 (37.8%) and 2.1.7 (20%) being most prevalent. Genotype 3.2.1 formed an independent lineage due to mutations in the quinolone resistance-determining region (QRDR). The multidrug-resistant haplotype 58 (genotype 4.3.1) has been present since 2006. <em>S.</em> Paratyphi A isolates were predominantly genotype 2.3.3 (98.5%). Pathogen exchange occurred with at least four other provinces. A cutoff of ≤3 single nucleotide polymorphisms (SNPs) was effective for outbreak investigation, and 22 genomic clusters were found, suggesting undetected outbreaks or transmission events. While 80% of isolates were susceptible to first-line antibiotics, 16.9% of <em>S.</em> Paratyphi <em>A</em> isolates were multidrug-resistant.</div></div><div><h3>Conclusions</h3><div>This study provides insights into the transmission dynamics of enteric fever in Shenzhen, underscoring the need for ongoing genomic surveillance to manage and control outbreaks effectively.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106469"},"PeriodicalIF":14.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding the Effectiveness of the Comirnaty Monovalent and Bivalent Vaccines During the Winter Coronavirus (COVID-19) Infection Survey.

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-05 DOI: 10.1016/j.jinf.2025.106461

Thomas Ward, Robert S Paton, Christopher E Overton, Jonathon Mellor, Nurin Abdul Aziz, Andre Charlett, Martyn Fyles

Background: Understanding the effectiveness of SARS-CoV-2 vaccines over time is critical for informing booster strategies, vaccine types, and public health policies, particularly with continued emergence of novel SARS-CoV-2 variants.

Methods: The Winter Coronavirus (COVID-19) Infection Study (WCIS), conducted from November 2023 to March 2024, involved approximately 150,000 participants aged 3 years and older from England and Scotland. The WCIS tested participants at regular intervals for SARS-CoV-2 using lateral flow tests to estimate prevalence and incidence in near real-time. Survival analysis using Cox proportional hazards regression was conducted, using WCIS data linked to participant vaccination records, to evaluate the association between time since vaccination and the risk of SARS-CoV-2 infection and symptomatic infection. Vaccine effectiveness (VE) was evaluated for the Comirnaty Omicron XBB.1.5 and Comirnaty Omicron BA.5 vaccines for those aged 65 years old and over. The model incorporated time-varying covariates within the counting process framework, stratified baseline hazards by age group, region, and time, and included key covariates such as sex, clinical risk status, ethnicity, and socioeconomic indicators. VE was estimated from hazard ratios, and penalised cubic splines were used to capture the nonlinear effects of time since vaccination.

Results: We estimated that the VE for the Comirnaty Omicron XBB.1.5 vaccine peaked at day 14 post-vaccination, reaching 70.63% (95% Confidence Intervals (CI): 43.33%, 84.78%) against infection and 63.62% (95% CI: 22.69%, 82.88%) against symptomatic infection. VE declined rapidly and by approximately weeks 9-12 post vaccination, the VE point estimates were close to zero with considerable uncertainty in the estimates from day 60 onwards. In contrast, the Comirnaty Omicron BA.5 bivalent vaccine showed no evidence of effectiveness within the study period, with VE estimates close to zero and wide confidence intervals crossing zero.

Conclusions: These findings provide important insights into the effectiveness of targeted vaccine strategies in the context of an evolving pandemic. As SARS-CoV-2 continues to mutate, adaptive approaches in vaccine design and public health policy will be key to addressing emerging variants and protecting high-risk groups.

{"title":"Understanding the Effectiveness of the Comirnaty Monovalent and Bivalent Vaccines During the Winter Coronavirus (COVID-19) Infection Survey.","authors":"Thomas Ward, Robert S Paton, Christopher E Overton, Jonathon Mellor, Nurin Abdul Aziz, Andre Charlett, Martyn Fyles","doi":"10.1016/j.jinf.2025.106461","DOIUrl":"https://doi.org/10.1016/j.jinf.2025.106461","url":null,"abstract":"<p><strong>Background: </strong>Understanding the effectiveness of SARS-CoV-2 vaccines over time is critical for informing booster strategies, vaccine types, and public health policies, particularly with continued emergence of novel SARS-CoV-2 variants.</p><p><strong>Methods: </strong>The Winter Coronavirus (COVID-19) Infection Study (WCIS), conducted from November 2023 to March 2024, involved approximately 150,000 participants aged 3 years and older from England and Scotland. The WCIS tested participants at regular intervals for SARS-CoV-2 using lateral flow tests to estimate prevalence and incidence in near real-time. Survival analysis using Cox proportional hazards regression was conducted, using WCIS data linked to participant vaccination records, to evaluate the association between time since vaccination and the risk of SARS-CoV-2 infection and symptomatic infection. Vaccine effectiveness (VE) was evaluated for the Comirnaty Omicron XBB.1.5 and Comirnaty Omicron BA.5 vaccines for those aged 65 years old and over. The model incorporated time-varying covariates within the counting process framework, stratified baseline hazards by age group, region, and time, and included key covariates such as sex, clinical risk status, ethnicity, and socioeconomic indicators. VE was estimated from hazard ratios, and penalised cubic splines were used to capture the nonlinear effects of time since vaccination.</p><p><strong>Results: </strong>We estimated that the VE for the Comirnaty Omicron XBB.1.5 vaccine peaked at day 14 post-vaccination, reaching 70.63% (95% Confidence Intervals (CI): 43.33%, 84.78%) against infection and 63.62% (95% CI: 22.69%, 82.88%) against symptomatic infection. VE declined rapidly and by approximately weeks 9-12 post vaccination, the VE point estimates were close to zero with considerable uncertainty in the estimates from day 60 onwards. In contrast, the Comirnaty Omicron BA.5 bivalent vaccine showed no evidence of effectiveness within the study period, with VE estimates close to zero and wide confidence intervals crossing zero.</p><p><strong>Conclusions: </strong>These findings provide important insights into the effectiveness of targeted vaccine strategies in the context of an evolving pandemic. As SARS-CoV-2 continues to mutate, adaptive approaches in vaccine design and public health policy will be key to addressing emerging variants and protecting high-risk groups.</p>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":" ","pages":"106461"},"PeriodicalIF":14.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587977","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}

引用次数: 0

Direct-acting antiviral treatment outcomes in people infected with endemic compared to epidemic hepatitis C virus subtypes in England

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-05 DOI: 10.1016/j.jinf.2025.106465

Laura T. Phillips , Daniel Bradshaw , Simon Packer , Ruth Simmons , Rare HCV Subtypes Group , William M. Rosenberg , Caroline A. Sabin , Jean L. Mbisa

Background

Current evidence suggests reduced efficacy of direct-acting antiviral (DAA) treatment among people with endemic Hepatitis C virus (HCV) subtypes rare to high-income countries. We aimed to determine real-world DAA treatment outcomes of people with endemic HCV subtypes in England.

Methods

Data were collected through a national treatment program. People who had their virus subtyped between 2019–2023, were resident in England and had an outcome recorded for their first DAA treatment episode, were included. Subtypes were divided into epidemic and endemic in England; endemic subtypes were confirmed with whole genome sequencing and resistance associated substitutions (RAS) were determined. Logistic regression was used to determine associations between treatment outcome and exposure variables.

Results

In people with an outcome recorded, 93 with an endemic and 8671 with an epidemic HCV subtype were identified, of whom 49.5% (46/93) and 91.8% (7953/8668) achieved a sustained virological response at 12 weeks post end of DAA treatment (SVR12), respectively. In the multivariable model, people with an endemic subtype had 93% (aOR 0.07 95%CI 0.04–0.12, P=<0.001) reduced odds of achieving SVR12. Treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir was successful for genotypes 1, 2, 4 and 5 (SVR12 100%, n=13) but not 3 (27.3%, n=22) endemic subtypes. Sofosbuvir/velpatasvir/voxilaprevir was successful for GT3 endemic subtypes at retreatment (SVR12 11/12, 91.7%). Treatment failures for genotypes 1, 3 and 4 were likely mediated by naturally occurring baseline NS5A RAS (median n=2).

Discussion

This study provides further evidence that endemic HCV subtypes lead to sub-optimal DAA efficacy, which may impact global HCV elimination.

{"title":"Direct-acting antiviral treatment outcomes in people infected with endemic compared to epidemic hepatitis C virus subtypes in England","authors":"Laura T. Phillips , Daniel Bradshaw , Simon Packer , Ruth Simmons , Rare HCV Subtypes Group , William M. Rosenberg , Caroline A. Sabin , Jean L. Mbisa","doi":"10.1016/j.jinf.2025.106465","DOIUrl":"10.1016/j.jinf.2025.106465","url":null,"abstract":"<div><h3>Background</h3><div>Current evidence suggests reduced efficacy of direct-acting antiviral (DAA) treatment among people with endemic Hepatitis C virus (HCV) subtypes rare to high-income countries. We aimed to determine real-world DAA treatment outcomes of people with endemic HCV subtypes in England.</div></div><div><h3>Methods</h3><div>Data were collected through a national treatment program. People who had their virus subtyped between 2019–2023, were resident in England and had an outcome recorded for their first DAA treatment episode, were included. Subtypes were divided into epidemic and endemic in England; endemic subtypes were confirmed with whole genome sequencing and resistance associated substitutions (RAS) were determined. Logistic regression was used to determine associations between treatment outcome and exposure variables.</div></div><div><h3>Results</h3><div>In people with an outcome recorded, 93 with an endemic and 8671 with an epidemic HCV subtype were identified, of whom 49.5% (46/93) and 91.8% (7953/8668) achieved a sustained virological response at 12 weeks post end of DAA treatment (SVR12), respectively. In the multivariable model, people with an endemic subtype had 93% (aOR 0.07 95%CI 0.04–0.12, P=<0.001) reduced odds of achieving SVR12. Treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir was successful for genotypes 1, 2, 4 and 5 (SVR12 100%, n=13) but not 3 (27.3%, n=22) endemic subtypes. Sofosbuvir/velpatasvir/voxilaprevir was successful for GT3 endemic subtypes at retreatment (SVR12 11/12, 91.7%). Treatment failures for genotypes 1, 3 and 4 were likely mediated by naturally occurring baseline NS5A RAS (median n=2).</div></div><div><h3>Discussion</h3><div>This study provides further evidence that endemic HCV subtypes lead to sub-optimal DAA efficacy, which may impact global HCV elimination.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106465"},"PeriodicalIF":14.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevalence and risk factors for Staphylococcus aureus colonisation among healthy individuals in low- and middle-income countries: A systematic review and meta-analysis.

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-05 DOI: 10.1016/j.jinf.2025.106462

Thomas E Locke, Alexander J Keeley, Nicholas Laundy, Christopher Keil, Jean Hamilton, Abdullah Pandor, Thushan I de Silva, Thomas C Darton

Background: Staphylococcus aureus is capable of asymptomatic colonisation, which can progress to opportunistic and potentially life-threatening infection. The data on S. aureus colonisation in low- and middle-income countries (LMIC) are limited. This systematic review and meta-analysis estimates the prevalence of S. aureus colonisation in asymptomatic individuals in LMIC, with secondary objectives of assessing antimicrobial resistance, colonisation risk factors, and the molecular epidemiology of colonising strains.

Methods: Articles published up to July 2023 were identified by searching four electronic databases. Studies that presented S. aureus colonisation prevalence in healthy individuals from a community setting in LMIC were included. Data extraction was performed independently by two reviewers with disagreement resolved through consensus. Studies were critically appraised using the Joanna Briggs Institute Prevalence tool. Random effects meta-analysis was conducted where appropriate. This study was registered in advance with PROSPERO (CRD42019147780).

Findings: A total of 16 610 citations were identified of which 138 studies (59 732 participants) met the eligibility criteria. The majority of studies had a low risk of bias. The pooled prevalence of S. aureus colonisation at nose and/or throat sites was 26·4% (95% CI 23·8 - 29·1%). The prevalence of methicillin-resistance in colonising S. aureus strains was 15·0% (95% CI: 11·8 to 18·6%), with a higher prevalence observed in Africa compared to Asia and South America (22·5% vs. 13·1% vs. 5·4% respectively). Panton-Valentine leukocidin genes were present in 26·4% (95% CI: 17·1% to 32·8%) of 2531 isolates.

Interpretation: While the prevalence of asymptomatic S. aureus colonisation in LMIC mirrors that found in high-income countries, there was a higher prevalence of antimicrobial resistance and other virulence factors. Variability in study methods and sparsity of data from many LMIC, underscore the need for a global approach to S. aureus surveillance. This will be critical for informing effective infection prevention strategies.

{"title":"Prevalence and risk factors for Staphylococcus aureus colonisation among healthy individuals in low- and middle-income countries: A systematic review and meta-analysis.","authors":"Thomas E Locke, Alexander J Keeley, Nicholas Laundy, Christopher Keil, Jean Hamilton, Abdullah Pandor, Thushan I de Silva, Thomas C Darton","doi":"10.1016/j.jinf.2025.106462","DOIUrl":"10.1016/j.jinf.2025.106462","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus is capable of asymptomatic colonisation, which can progress to opportunistic and potentially life-threatening infection. The data on S. aureus colonisation in low- and middle-income countries (LMIC) are limited. This systematic review and meta-analysis estimates the prevalence of S. aureus colonisation in asymptomatic individuals in LMIC, with secondary objectives of assessing antimicrobial resistance, colonisation risk factors, and the molecular epidemiology of colonising strains.</p><p><strong>Methods: </strong>Articles published up to July 2023 were identified by searching four electronic databases. Studies that presented S. aureus colonisation prevalence in healthy individuals from a community setting in LMIC were included. Data extraction was performed independently by two reviewers with disagreement resolved through consensus. Studies were critically appraised using the Joanna Briggs Institute Prevalence tool. Random effects meta-analysis was conducted where appropriate. This study was registered in advance with PROSPERO (CRD42019147780).</p><p><strong>Findings: </strong>A total of 16 610 citations were identified of which 138 studies (59 732 participants) met the eligibility criteria. The majority of studies had a low risk of bias. The pooled prevalence of S. aureus colonisation at nose and/or throat sites was 26·4% (95% CI 23·8 - 29·1%). The prevalence of methicillin-resistance in colonising S. aureus strains was 15·0% (95% CI: 11·8 to 18·6%), with a higher prevalence observed in Africa compared to Asia and South America (22·5% vs. 13·1% vs. 5·4% respectively). Panton-Valentine leukocidin genes were present in 26·4% (95% CI: 17·1% to 32·8%) of 2531 isolates.</p><p><strong>Interpretation: </strong>While the prevalence of asymptomatic S. aureus colonisation in LMIC mirrors that found in high-income countries, there was a higher prevalence of antimicrobial resistance and other virulence factors. Variability in study methods and sparsity of data from many LMIC, underscore the need for a global approach to S. aureus surveillance. This will be critical for informing effective infection prevention strategies.</p>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":" ","pages":"106462"},"PeriodicalIF":14.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587960","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}

引用次数: 0

A human-infecting H10N5 avian influenza virus: Clinical features, virus reassortment, receptor-binding affinity, and possible transmission routes

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-04 DOI: 10.1016/j.jinf.2025.106456

Jing Yang , Shufa Zheng , Ju Sun , Haibo Wu , Dan Zhang , Yanjun Wang , Tian Tian , Linwei Zhu , Zhigang Wu , Lanjuan Li , George F. Gao , Yuhai Bi , Hangping Yao

Background

In late 2023, the first human case caused by an H10N5 avian influenza virus (AIV) was diagnosed in China. H10Ny AIVs have been identified in various poultry and wild birds in Eurasia, the Americas, and Oceania.

Methods

We analyzed the clinical data of the H10N5 AIV-infected patient, isolated the virus, and evaluated the virus receptor-binding properties together with the H10N8 and H10N3 AIVs identified in humans and poultry. The genomic data of the human-infecting H10N5 strain and avian H10Ny AIVs (n = 48, including 16 strains of H10N3 and 2 strains of H10N8) from live poultry markets in China, during 2019–2021, were sequenced. We inferred the genetic origin and spread pattern of the H10N5 AIV using the phylodynamic methods. In addition, given all available nucleotide sequences, the spatial-temporal dynamics, host distribution, and the maximum-likelihood phylogenies of global H10 AIVs were reconstructed.

Findings

The first H10N5 AIV-infected human case co-infected with seasonal influenza H3N2 virus was identified. Unfortunately, the patient died after systematic treatments. The H10N5 virus predominantly bound avian-type receptor, without any known mammalian-adapted mutations. Phylodynamic inference indicated that the H10N5 AIV was generated by multiple reassortments among viruses from Korea and Japan, central Asia, and China in late 2022, acquiring the seven gene segments from H10N7 or other low pathogenic AIVs in wild Anseriformes, except for the PA gene from H5N2 AIVs in Domestic Anseriformes. The HA gene of the H10N5 virus belongs to the North American lineage, which was probably introduced into Asia by migratory birds, subsequently forming local circulation.

Interpretation

Unlike the human-infecting H10N3 and H10N8 AIVs acquiring six internal protein-coding genes from H9N2 AIVs in domestic poultry, the human-infecting H10N5 AIV was generated through multiple reassortments among viruses mainly carried by wild Anseriformes. Furthermore, worldwide distribution, inter-continental transmission, and genetic exchanges between Eurasian and North American lineages call for more concerns about influenza surveillance on H10Ny AIVs, especially in the flyway overlapping areas.

{"title":"A human-infecting H10N5 avian influenza virus: Clinical features, virus reassortment, receptor-binding affinity, and possible transmission routes","authors":"Jing Yang , Shufa Zheng , Ju Sun , Haibo Wu , Dan Zhang , Yanjun Wang , Tian Tian , Linwei Zhu , Zhigang Wu , Lanjuan Li , George F. Gao , Yuhai Bi , Hangping Yao","doi":"10.1016/j.jinf.2025.106456","DOIUrl":"10.1016/j.jinf.2025.106456","url":null,"abstract":"<div><h3>Background</h3><div>In late 2023, the first human case caused by an H10N5 avian influenza virus (AIV) was diagnosed in China. H10Ny AIVs have been identified in various poultry and wild birds in Eurasia, the Americas, and Oceania.</div></div><div><h3>Methods</h3><div>We analyzed the clinical data of the H10N5 AIV-infected patient, isolated the virus, and evaluated the virus receptor-binding properties together with the H10N8 and H10N3 AIVs identified in humans and poultry. The genomic data of the human-infecting H10N5 strain and avian H10Ny AIVs (n = 48, including 16 strains of H10N3 and 2 strains of H10N8) from live poultry markets in China, during 2019–2021, were sequenced. We inferred the genetic origin and spread pattern of the H10N5 AIV using the phylodynamic methods. In addition, given all available nucleotide sequences, the spatial-temporal dynamics, host distribution, and the maximum-likelihood phylogenies of global H10 AIVs were reconstructed.</div></div><div><h3>Findings</h3><div>The first H10N5 AIV-infected human case co-infected with seasonal influenza H3N2 virus was identified. Unfortunately, the patient died after systematic treatments. The H10N5 virus predominantly bound avian-type receptor, without any known mammalian-adapted mutations. Phylodynamic inference indicated that the H10N5 AIV was generated by multiple reassortments among viruses from Korea and Japan, central Asia, and China in late 2022, acquiring the seven gene segments from H10N7 or other low pathogenic AIVs in wild <em>Anseriformes,</em> except for the PA gene from H5N2 AIVs in Domestic <em>Anseriformes</em>. The HA gene of the H10N5 virus belongs to the North American lineage, which was probably introduced into Asia by migratory birds, subsequently forming local circulation.</div></div><div><h3>Interpretation</h3><div>Unlike the human-infecting H10N3 and H10N8 AIVs acquiring six internal protein-coding genes from H9N2 AIVs in domestic poultry, the human-infecting H10N5 AIV was generated through multiple reassortments among viruses mainly carried by wild <em>Anseriformes</em>. Furthermore, worldwide distribution, inter-continental transmission, and genetic exchanges between Eurasian and North American lineages call for more concerns about influenza surveillance on H10Ny AIVs, especially in the flyway overlapping areas.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106456"},"PeriodicalIF":14.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of lesion bioactivity in hepatic cystic echinococcosis using a transformer-based fusion model

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-04 DOI: 10.1016/j.jinf.2025.106455

Zhanjin Wang , Fuyuan Li , Junjie Cai , Zhangtuo Xue , Kaihao Du , Yongping Tao , Hanxi Zhang , Ying Zhou , Haining Fan , Zhan Wang

Background

Differentiating whether hepatic cystic echinococcosis (HCE) lesions exhibit biological activity is essential for developing effective treatment plans. This study evaluates the performance of a Transformer-based fusion model in assessing HCE lesion activity.

Methods

This study analyzed CT images and clinical variables from 700 HCE patients across three hospitals from 2018 to 2023. Univariate and multivariate logistic regression analyses were conducted for the selection of clinical variables to construct a clinical model. Radiomics features were extracted from CT images using Pyradiomics to develop a radiomics model. Additionally, a 2D deep learning model and a 3D deep learning model were trained using the CT images. The fusion model was constructed using feature-level fusion, decision-level fusion, and a Transformer network architecture, allowing for the analysis of the discriminative ability and correlation among radiomics features, 2D deep learning features, and 3D deep learning features, while comparing the classification performance of the three multimodal fusion models.

Results

In comparison to radiomics and 2D deep learning features, the 3D deep learning features exhibited superior discriminative ability in identifying the biological activity of HCE lesions. The Transformer-based fusion model demonstrated the highest performance in both the internal validation set and the external validation set, achieving AUC values of 0.997 (0.992–1.000) and 0.944 (0.911–0.977), respectively, thereby outperforming both the feature-level and decision-level fusion models, and enabling precise differentiation of HCE lesion biological activity.

Conclusion

The Transformer multimodal fusion model integrates clinical features, radiomics features, and both 2D and 3D deep learning features, facilitating accurate differentiation of the biological activity of HCE lesions and exhibiting significant potential for clinical application.

背景：区分肝囊性棘球蚴病（HCE）病变是否具有生物活性对于制定有效的治疗方案至关重要。本研究评估了基于 Transformer 的融合模型在预测 HCE 病变活性方面的性能：本研究分析了2018年至2023年三家医院700名HCE患者的CT图像和临床变量。对临床变量的选择进行了单变量和多变量逻辑回归分析，以构建临床模型。使用 Pyradiomics 从 CT 图像中提取放射组学特征，以建立放射组学模型。此外，还利用 CT 图像训练了二维深度学习模型和三维深度学习模型。融合模型的构建采用了特征级融合、决策级融合和Transformer网络架构，可以分析放射组学特征、二维深度学习特征和三维深度学习特征之间的判别能力和相关性，同时比较三种多模态融合模型的分类性能：结果：与放射学特征和二维深度学习特征相比，三维深度学习特征在识别 HCE 病变的生物活性方面表现出更优越的鉴别能力。基于Transformer的融合模型在测试集和外部验证集上都表现出了最高的性能，AUC值分别达到了0.997（0.992-1.000）和0.944（0.911-0.977），从而超越了特征级和决策级融合模型，实现了对HCE病变生物活性的精确区分：Transformer多模态融合模型整合了临床特征、放射学特征以及二维和三维深度学习特征，有助于准确区分HCE病变的生物活性，具有巨大的临床应用潜力。

{"title":"Identification of lesion bioactivity in hepatic cystic echinococcosis using a transformer-based fusion model","authors":"Zhanjin Wang , Fuyuan Li , Junjie Cai , Zhangtuo Xue , Kaihao Du , Yongping Tao , Hanxi Zhang , Ying Zhou , Haining Fan , Zhan Wang","doi":"10.1016/j.jinf.2025.106455","DOIUrl":"10.1016/j.jinf.2025.106455","url":null,"abstract":"<div><h3>Background</h3><div>Differentiating whether hepatic cystic echinococcosis (HCE) lesions exhibit biological activity is essential for developing effective treatment plans. This study evaluates the performance of a Transformer-based fusion model in assessing HCE lesion activity.</div></div><div><h3>Methods</h3><div>This study analyzed CT images and clinical variables from 700 HCE patients across three hospitals from 2018 to 2023. Univariate and multivariate logistic regression analyses were conducted for the selection of clinical variables to construct a clinical model. Radiomics features were extracted from CT images using Pyradiomics to develop a radiomics model. Additionally, a 2D deep learning model and a 3D deep learning model were trained using the CT images. The fusion model was constructed using feature-level fusion, decision-level fusion, and a Transformer network architecture, allowing for the analysis of the discriminative ability and correlation among radiomics features, 2D deep learning features, and 3D deep learning features, while comparing the classification performance of the three multimodal fusion models.</div></div><div><h3>Results</h3><div>In comparison to radiomics and 2D deep learning features, the 3D deep learning features exhibited superior discriminative ability in identifying the biological activity of HCE lesions. The Transformer-based fusion model demonstrated the highest performance in both the internal validation set and the external validation set, achieving AUC values of 0.997 (0.992–1.000) and 0.944 (0.911–0.977), respectively, thereby outperforming both the feature-level and decision-level fusion models, and enabling precise differentiation of HCE lesion biological activity.</div></div><div><h3>Conclusion</h3><div>The Transformer multimodal fusion model integrates clinical features, radiomics features, and both 2D and 3D deep learning features, facilitating accurate differentiation of the biological activity of HCE lesions and exhibiting significant potential for clinical application.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106455"},"PeriodicalIF":14.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An artificial intelligence tool that may assist with interpretation of rapid plasma reagin test for syphilis: Development and on-site evaluation

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-03 DOI: 10.1016/j.jinf.2025.106454

Jiaxuan Jin , Yan Han , Yueping Yin , Bangyong Zhu , Guanqun Wang , Wenjie Lu , Hongchun Wang , Kai Chen , Xiaoyu Zhu , Wenqi Xu , Hedan Yang , Xiangsheng Chen , Yin Yang , Tong Lin

Objectives

The rapid plasma reagin (RPR) test, a traditional method for diagnosing syphilis and evaluating treatment efficacy, relies on subjective interpretation and requires high technical proficiency. This study aimed to develop and validate a user-friendly RPR-artificial intelligence (AI) interpretative tool.

Methods

A dataset comprising 600 images of photographed RPR cards from 276 negative and 223 positive RPR samples was used for model development. The reference result was based on consistent interpretations by at least two out of three experienced laboratory personnel. Then an interpretative model was developed using deep learning algorithms and loaded into smartphones for on-site interpretation at two clinical centers from October 2023 to April 2024.

Results

The model demonstrated an accuracy of 82·67% (95% CI 71·82%–90·09%) for reactive circles and 84·44% (95% CI 69·94%–93·01%) for non-reactive circles. In the field study, 669 specimens showed a sensitivity of 94·85% (95% CI 89·29%–97·73%), specificity of 91·56% (95% CI 88·78%–93·71%), and concordance of 92·23% (95% CI 89·87%–94·09%). The positive predictive value was 74·14% (95% CI 66·86%–80·33%) and negative predictive value was 98.59% (95% CI 96·98%–99·38%).

Conclusions

The tool assists in RPR interpretation standardization, enabling data traceability, and quality control for remote and underdeveloped areas.

{"title":"An artificial intelligence tool that may assist with interpretation of rapid plasma reagin test for syphilis: Development and on-site evaluation","authors":"Jiaxuan Jin , Yan Han , Yueping Yin , Bangyong Zhu , Guanqun Wang , Wenjie Lu , Hongchun Wang , Kai Chen , Xiaoyu Zhu , Wenqi Xu , Hedan Yang , Xiangsheng Chen , Yin Yang , Tong Lin","doi":"10.1016/j.jinf.2025.106454","DOIUrl":"10.1016/j.jinf.2025.106454","url":null,"abstract":"<div><h3>Objectives</h3><div>The rapid plasma reagin (RPR) test, a traditional method for diagnosing syphilis and evaluating treatment efficacy, relies on subjective interpretation and requires high technical proficiency. This study aimed to develop and validate a user-friendly RPR-artificial intelligence (AI) interpretative tool.</div></div><div><h3>Methods</h3><div>A dataset comprising 600 images of photographed RPR cards from 276 negative and 223 positive RPR samples was used for model development. The reference result was based on consistent interpretations by at least two out of three experienced laboratory personnel. Then an interpretative model was developed using deep learning algorithms and loaded into smartphones for on-site interpretation at two clinical centers from October 2023 to April 2024.</div></div><div><h3>Results</h3><div>The model demonstrated an accuracy of 82·67% (95% CI 71·82%–90·09%) for reactive circles and 84·44% (95% CI 69·94%–93·01%) for non-reactive circles. In the field study, 669 specimens showed a sensitivity of 94·85% (95% CI 89·29%–97·73%), specificity of 91·56% (95% CI 88·78%–93·71%), and concordance of 92·23% (95% CI 89·87%–94·09%). The positive predictive value was 74·14% (95% CI 66·86%–80·33%) and negative predictive value was 98.59% (95% CI 96·98%–99·38%).</div></div><div><h3>Conclusions</h3><div>The tool assists in RPR interpretation standardization, enabling data traceability, and quality control for remote and underdeveloped areas.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106454"},"PeriodicalIF":14.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The spread of CTX-M-type extended-spectrum beta-lactamases in China: Epidemiology and evolutionary analyses

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-03 DOI: 10.1016/j.jinf.2025.106457

Keyi Yu , Zhenzhou Huang , Xiao Liu , He Gao , Xuemei Bai , Zhiwen Sun , Duochun Wang

CTX-M-type extended-spectrum beta-lactamases (ESBLs) have shown a high level of global transmission, with limited systematic understanding of their epidemic patterns in China. A comprehensive analysis covering 1974–2023 identified 133 (3.2%) bla_CTX-Ms-producing strains among 4146 strains from 25 Chinese cities across 82 genera were performed. Integrating with public database strains (n=431), the study comprised 564 bla_CTX-Ms-positive isolates sourced from 19 provinces (1986–2022) including 300 (53.2%) clinical and 228 (40.4%) environmental bla_CTX-Ms. The most frequent sources of infection were diarrhea (44%), upper respiratory tract infection (22.2%) and urinary tract infection (14%). Phylogenetic studies indicated CTX-M-1 and CTX-M-9 emerged as the predominant subgroups. Lineages exhibited diverse mutation sites without being restricted by geographical conditions. Ka/Ks ratio distribution varied significantly among lineages (P<0.05). Lineages 1 (L1) and L2 were characterized by neutral or purifying selection, whereas L3 was mainly under purifying selection. Adaptive evolution was noted at different loci within each lineage. The influence of geographic distance on phylogeny varied distinctly across different lineages. Notably, for Lineage L3, there was a remarkably strong correlation observed, which implies that human activities exerted a more substantial influence on genetic distances compared to geography. This research provides valuable insights into the epidemiology, genotypic diversity, and evolutionary traits of bla_CTX-Ms in China, supporting health risk assessment for early warning systems.

{"title":"The spread of CTX-M-type extended-spectrum beta-lactamases in China: Epidemiology and evolutionary analyses","authors":"Keyi Yu , Zhenzhou Huang , Xiao Liu , He Gao , Xuemei Bai , Zhiwen Sun , Duochun Wang","doi":"10.1016/j.jinf.2025.106457","DOIUrl":"10.1016/j.jinf.2025.106457","url":null,"abstract":"<div><div>CTX-M-type extended-spectrum beta-lactamases (ESBLs) have shown a high level of global transmission, with limited systematic understanding of their epidemic patterns in China. A comprehensive analysis covering 1974–2023 identified 133 (3.2%) <em>bla</em><sub>CTX-Ms</sub>-producing strains among 4146 strains from 25 Chinese cities across 82 genera were performed. Integrating with public database strains (n=431), the study comprised 564 <em>bla</em><sub>CTX-Ms</sub>-positive isolates sourced from 19 provinces (1986–2022) including 300 (53.2%) clinical and 228 (40.4%) environmental <em>bla</em><sub>CTX-Ms</sub>. The most frequent sources of infection were diarrhea (44%), upper respiratory tract infection (22.2%) and urinary tract infection (14%). Phylogenetic studies indicated CTX-M-1 and CTX-M-9 emerged as the predominant subgroups. Lineages exhibited diverse mutation sites without being restricted by geographical conditions. Ka/Ks ratio distribution varied significantly among lineages (<em>P</em><0.05). Lineages 1 (L1) and L2 were characterized by neutral or purifying selection, whereas L3 was mainly under purifying selection. Adaptive evolution was noted at different loci within each lineage. The influence of geographic distance on phylogeny varied distinctly across different lineages. Notably, for Lineage L3, there was a remarkably strong correlation observed, which implies that human activities exerted a more substantial influence on genetic distances compared to geography. This research provides valuable insights into the epidemiology, genotypic diversity, and evolutionary traits of <em>bla</em><sub>CTX-Ms</sub> in China, supporting health risk assessment for early warning systems.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106457"},"PeriodicalIF":14.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Host-derived Delta-like Canonical Notch ligand-1 in sepsis and septic shock: Infection site, pathogens and disease severity matter – Secondary analysis of data from a randomized controlled trial

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2025-03-03 DOI: 10.1016/j.jinf.2025.106458

Vivienne Theobald , Frank Bloos , Michael Bauer , Thorsten Brenner , Maik von der Forst , Patrick Meybohm , Judith Schenz , Felix C.F. Schmitt , Benedikt Siegler , Markus A. Weigand , Maximilian Dietrich , for the SepNet Critical Care Trials Group

Background

Sepsis is a life-threatening condition and many biomarkers for diagnosing and treatment guidance have been investigated in recent years. However, new ones are emerging almost daily, only few markers with diagnostic value have passed to entered clinical routine application. Delta-like canonical Notch ligand-1 (DLL-1) seems to be a potential contributor in the differentiation between sepsis and non-septic infection. Its role for clinical application and potential septic outcome prediction is yet unclear.

Methods

This study is a secondary analysis of data and DLL-1 measurements from plasma samples obtained in the SISPCT trial. Primary objective of this explorative study was to investigate the difference of DLL-1 values between patients with sepsis and septic shock. Secondary objectives were the differences in DLL-1 levels in patients with different blood culture results, with infections caused by different pathogens, by origin of infection and disease severity. Furthermore, the study investigated the use of DLL-1 for in-hospital and intensive care unit (ICU) mortality prediction. Therefore, data from 1.027 patients were analyzed.

Results

DLL-1 values were significantly higher in patients with septic shock than in septic patients (13,003 ± 7695 pg/mL and 9257 ± 4188 pg/mL, p<0.001). Patients with abdominal infections, primary bacteremia or surgical wound infections exhibited the highest DLL-1 values. In addition, patients with gram-negative pathogens had significantly higher DLL-1 levels than those with specific gram-positive pathogens or negative blood cultures (p<0.001). Infections caused by Escherichia coli, Enterobacterales, and Staphylococcus aureus were associated with the highest DLL-1 levels (18,341 pg/mL, (12,968; 23,250), 21,556 pg/mL (14,386; 30,939) and 16,352 pg/mL (11,905; 25,853), respectively). DLL-1 levels correlated with increasing SOFA scores and demonstrated predictive value for in-hospital and ICU mortality, with an AUC of 0.7, outperforming lactate and procalcitonin.

Conclusion

Delta-like canonical Notch ligand-1 (DLL-1) is increased in septic shock compared to sepsis. Its elevation appears to be dependent on the infection focus, the triggering pathogen and the disease severity. Furthermore, it has a predictive value for mortality.

{"title":"Host-derived Delta-like Canonical Notch ligand-1 in sepsis and septic shock: Infection site, pathogens and disease severity matter – Secondary analysis of data from a randomized controlled trial","authors":"Vivienne Theobald , Frank Bloos , Michael Bauer , Thorsten Brenner , Maik von der Forst , Patrick Meybohm , Judith Schenz , Felix C.F. Schmitt , Benedikt Siegler , Markus A. Weigand , Maximilian Dietrich , for the SepNet Critical Care Trials Group","doi":"10.1016/j.jinf.2025.106458","DOIUrl":"10.1016/j.jinf.2025.106458","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is a life-threatening condition and many biomarkers for diagnosing and treatment guidance have been investigated in recent years. However, new ones are emerging almost daily, only few markers with diagnostic value have passed to entered clinical routine application. Delta-like canonical Notch ligand-1 (DLL-1) seems to be a potential contributor in the differentiation between sepsis and non-septic infection. Its role for clinical application and potential septic outcome prediction is yet unclear.</div></div><div><h3>Methods</h3><div>This study is a secondary analysis of data and DLL-1 measurements from plasma samples obtained in the SISPCT trial. Primary objective of this explorative study was to investigate the difference of DLL-1 values between patients with sepsis and septic shock. Secondary objectives were the differences in DLL-1 levels in patients with different blood culture results, with infections caused by different pathogens, by origin of infection and disease severity. Furthermore, the study investigated the use of DLL-1 for in-hospital and intensive care unit (ICU) mortality prediction. Therefore, data from 1.027 patients were analyzed.</div></div><div><h3>Results</h3><div>DLL-1 values were significantly higher in patients with septic shock than in septic patients (13,003 ± 7695 pg/mL and 9257 ± 4188 pg/mL, p<0.001). Patients with abdominal infections, primary bacteremia or surgical wound infections exhibited the highest DLL-1 values. In addition, patients with gram-negative pathogens had significantly higher DLL-1 levels than those with specific gram-positive pathogens or negative blood cultures (p<0.001). Infections caused by <em>Escherichia coli</em>, Enterobacterales, and <em>Staphylococcus aureus</em> were associated with the highest DLL-1 levels (18,341 pg/mL, (12,968; 23,250), 21,556 pg/mL (14,386; 30,939) and 16,352 pg/mL (11,905; 25,853), respectively). DLL-1 levels correlated with increasing SOFA scores and demonstrated predictive value for in-hospital and ICU mortality, with an AUC of 0.7, outperforming lactate and procalcitonin.</div></div><div><h3>Conclusion</h3><div>Delta-like canonical Notch ligand-1 (DLL-1) is increased in septic shock compared to sepsis. Its elevation appears to be dependent on the infection focus, the triggering pathogen and the disease severity. Furthermore, it has a predictive value for mortality.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106458"},"PeriodicalIF":14.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0