Journal of Clinical Microbiology最新文献

{"title":"Identification of multiple arbovirus infections/exposure in Northeastern Brazil using a multiplex microsphere immunoassay.","authors":"Wei-Kung Wang, Eduardo Martins Netto, Szu-Chia Hsieh, Guan-Hua Chen, Melissa Barreto Falcão, Celia Pedroso, Rafaela Mayoral, Roger Costa, Yu-Ching Dai, Rennsilve C Salomon, Jih-Jin Tsai, Laíse de Moraes, Viviane Sampaio Boaventura, Ricardo Khouri, Carlos Brites","doi":"10.1128/jcm.00013-26","DOIUrl":"10.1128/jcm.00013-26","url":null,"abstract":"<p><p>Several mosquito-borne arboviruses, including dengue (DENV), Zika (ZIKV), West Nile (WNV), yellow fever (YFV), and chikungunya (CHIKV) viruses, have caused disease outbreaks of public health concern in the tropics and subtropics. The overlap distribution of these arboviruses and cross-reactivities of antibodies to orthoflavivirus envelope protein underscore the need for a reliable and convenient serological test to distinguish these arboviruses in endemic countries. We developed a multiplex IgG microsphere immunoassay (MIA) using 13 antigens to test 8 panels of samples with well-documented arbovirus infections or vaccination (<i>n</i> = 374). We further employed this assay, combined with previously reported neutralization test and Western blot analysis to test serum samples (<i>n</i> = 300) collected from Saúde, a town in the Northeastern state of Bahia, Brazil. The sensitivity/specificity of mixed DENV1-4, ZIKV, WNV, and YFV nonstructural protein 1 (NS1), and CHIKV virus-like particles (VLP) IgG MIAs were 96.0%/98.3%, 100%/79.9%, 94.4%/73.4%, 52.2%/94.4%, and 100%/99.7%, respectively. The overall low specificity of ZIKV and WNV NS1 was due to cross-reactivities from panels with repeated orthoflavivirus infections, including secondary DENV and DENV + ZIKV infections. In Saúde, we found seropositivity of 70.3%, 22.3%, 39.7%, and 5.7% to DENV, ZIKV, YFV, and CHIKV, respectively, and the majority with multiple arbovirus infections or exposure including DENV + CHIKV, DENV + ZIKV, DENV + YFV, DENV + ZIKV + YFV, and/or CHIKV. Our findings highlight the importance of confirmatory tests for the NS1-based multiplex IgG MIA. This high-throughput assay, combined with confirmatory tests, provides a labor-saving and validated tool for serodiagnosis and serosurveillance of pathogenic arbovirus infections/exposure in endemic regions.IMPORTANCESeveral multiplex microsphere immunoassays (MIA) have been reported to detect pathogenic arbovirus infections, including dengue (DENV), Zika (ZIKV), West Nile (WNV), yellow fever (YFV), and chikungunya (CHIKV) viruses. None of them included sufficient control panels to validate the sensitivity/specificity of each antigen, confirmatory tests for equivocal samples, or comparison with available commercial kits to advance this technology from research to practical use. We employed eight panels of samples with known arbovirus infections or vaccination (<i>n</i> = 374) to evaluate the sensitivity/specificity of our multiplex IgG MIA. We reported high sensitivity of nonstructural protein 1 (NS1)-based IgG MIA (94.4%-100% except YFV NS1) and overall low specificity of ZIKV and WNV NS1 due to cross-reactivities from repeated orthoflavivirus infections, including secondary DENV and DENV + ZIKV infections. Using our algorithm and confirmatory tests, we reported multiple arbovirus infections or exposure (DENV + ZIKV, DENV + YFV, DENV + ZIKV + YFV, and/or CHIKV) in the majority of participants from a town in Northeastern Brazil.<","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0001326"},"PeriodicalIF":5.4,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photo Quiz: A 69-year-old male presenting with a hepatic abscess.","authors":"Andrew Walkty, Markus Stein, Heather Adam, James Karlowsky, John Embil","doi":"10.1128/jcm.01430-25","DOIUrl":"https://doi.org/10.1128/jcm.01430-25","url":null,"abstract":"","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0143025"},"PeriodicalIF":5.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine and chemokine profiles linked to early severity of scrub typhus: multicenter validation of soluble PD-L1.","authors":"Dachuan Lin, Gaoyu Wang, Liyuan Zhang, Meng Chang, Hua Pei, Xiaoyuan Hu, Ruoyan Peng, Chuanning Tang, Yijia Guo, Siqi Chen, Nan Ge, Wenjun Tian, Fahui Wang, Yongguo Du, Shannan Wu, Yueping Wang, Long Sun, Biao Wu, Kwok-Yung Yuen, Jasper Fuk-Woo Chan, Min Liao, Feifei Yin","doi":"10.1128/jcm.01633-25","DOIUrl":"https://doi.org/10.1128/jcm.01633-25","url":null,"abstract":"<p><p>Early identification of patients at risk of developing severe disease remains a clinical challenge for scrub typhus. We aimed to identify serum cytokine profiles associated with disease severity and validate potential biomarkers for early risk stratification of patients with scrub typhus. We conducted a retrospective multicenter study to analyze serum cytokine/chemokine profiles and clinical data of 51 scrub typhus patients and 13 control patients at presentation to the hospital. We further performed longitudinal monitoring of the cytokine/chemokine dynamics in 11 of these patients. The findings were then validated in two different hospitals (<i>n</i> = 88). Of 44 cytokines/chemokines tested, 32 were detectable in the serum samples of the patients. Compared with control patients, patients with scrub typhus showed significant elevation of 22 and reductions of 3 cytokines/chemokines (<i>P</i> < 0.05). The serum soluble programmed death-ligand 1 (sPD-L1) levels differed significantly across severity groups (<i>P</i> = 0.04) and trended lower during recovery (<i>P</i> = 0.082). sPD-L1 demonstrated a significant trend with increasing severity and showed superior performance to conventional markers in distinguishing patients with organ dysfunction. Receiver operating characteristic analysis of sPD-L1 levels at hospital admission confirmed high discriminatory power, with AUCs of 0.997 and 0.981 in the two validation cohorts. This multicenter study identified sPD-L1 as a potential early biomarker for early risk stratification of patients with scrub typhus.</p><p><strong>Importance: </strong>Scrub typhus, caused by <i>Orientia tsutsugamushi</i>, affects over one million people annually in the Asia-Pacific region, with an in-hospital mortality rate of more than 30% among patients with severe disease. Early identification of patients at high risk of progression to multi-organ failure remains a major clinical challenge. Timely risk stratification to identify high-risk patients is essential to prevent poor clinical outcomes. This study identifies soluble programmed death-ligand 1 as a potential early biomarker that distinguishes patients at risk of developing severe disease within the first week of hospitalization.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0163325"},"PeriodicalIF":5.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MethylSense: high accuracy machine learning-based diagnostics for <i>Aspergillus fumigatus</i> infection in chickens using host cell-free DNA methylation and Nanopore sequencing.","authors":"Markus Hodal Drag, Christina Hvilsom, Louise Ladefoged Poulsen, Henrik Elvang Jensen, Stamatios Alan Tahas, Christoph Leineweber, Carolyn Cray, Mads Frost Bertelsen, Anders Miki Bojesen","doi":"10.1128/jcm.01054-25","DOIUrl":"https://doi.org/10.1128/jcm.01054-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Avian aspergillosis, caused by &lt;i&gt;Aspergillus fumigatus&lt;/i&gt; (&lt;i&gt;Af&lt;/i&gt;), lacks sensitive antemortem diagnostics. Existing microbial cell-free DNA (cfDNA) tests are prone to contamination and require a high pathogen load. We hypothesized that infection-induced tissue damage in chickens creates differentially methylated regions (DMRs) in host cfDNA, enabling machine learning (ML) diagnostics. Serum cfDNA samples (&lt;i&gt;n&lt;/i&gt; = 124) were obtained from broiler chickens (&lt;i&gt;n&lt;/i&gt; = 76) with &lt;i&gt;Af&lt;/i&gt; and non-&lt;i&gt;Af&lt;/i&gt; infections (&lt;i&gt;Escherichia coli&lt;/i&gt; or &lt;i&gt;Gallibacterium anatis&lt;/i&gt;) and controls. Oxford Nanopore sequencing enabled DMR detection and ML training. Performance was evaluated using an independent set (&lt;i&gt;n&lt;/i&gt; = 49) and 10-repeat Monte Carlo cross-validation (CV) (&lt;i&gt;n&lt;/i&gt; = 490 evaluations per test) as quality control. A High Accuracy test (93 DMRs, neural network) achieved 98.0% accuracy (sensitivity 95%, specificity 100%, AUC 0.974, PR-AUC 0.928) in the independent set, with CV accuracy 92.0% [95% CI: 89.7%-94.4%]. A Fast test (35 DMRs, SVM) achieved 81.6% accuracy and CV accuracy 79.6% [74.9%-84.3%]. An &lt;i&gt;In Situ&lt;/i&gt; test (5 DMRs, random forest) designed for field deployment achieved 71.4% accuracy and CV accuracy 62.9% [58.7%-67.0%]. Stratified CV accuracy showed 84.6% [65.1%-95.6%] correct classifications for &lt;i&gt;E. coli&lt;/i&gt; and 100% [80.5%-100%] for &lt;i&gt;G. anatis&lt;/i&gt;. Markers showed high bootstrap stability and predominantly overlapped EMARs and enhancers. In conclusion, we present MethylSense (https://github.com/markusdrag/MethylSense), an automated open-source software. The High Accuracy test achieved 92.0% [89.7%-94.4%] CV accuracy (CV sensitivity 94.5% [91.4%-97.6%], CV specificity 90.3% [87.8%-92.9%]). While validated in chickens, MethylSense is adaptable to other species and pathogens, offering scalable, contamination-resilient diagnostics for veterinary and conservation applications.IMPORTANCEMethylSense is an automated software for training machine learning diagnostics using differentially methylated regions (DMRs) in cell-free DNA from Oxford Nanopore sequencing. We applied MethylSense to develop three &lt;i&gt;Aspergillus fumigatus&lt;/i&gt; tests for chickens, each optimized for different clinical scenarios. The High Accuracy test (93 DMRs, neural network) demonstrated 98.0% accuracy, in a blinded test set (&lt;i&gt;n&lt;/i&gt; = 49) with sensitivity 95%, specificity 100%, ROC-AUC 0.974, and PR-AUC 0.928. Stratified 10-repeat Monte Carlo cross-validation (&lt;i&gt;n&lt;/i&gt; = 490) showed correct classifications of 84.6% [CI: 65.1%-95.6%] &lt;i&gt;Escherichia coli&lt;/i&gt; and 100% [80.5%-100%] &lt;i&gt;Gallibacterium anatis&lt;/i&gt; infected specificity samples. A Fast test for rapid &lt;1 h sequencing (35 DMRs, support vector machine) achieved 81.6% accuracy (sensitivity 80%, specificity 82.8%). An &lt;i&gt;In Situ&lt;/i&gt; test (5 DMRs, random forest) for field deployment via methylation-specific PCR achieved 71.4% accuracy (sensitivity 45%, specificity 89.7%). Bootstrap analysis demo","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0105425"},"PeriodicalIF":5.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional-local urinary antibiograms for long-term care homes: a population-wide cross-sectional study.","authors":"Bradley J Langford, Kevin A Brown, Sarah Swayze, Lucas Castellani, Dan Dalton, Fiona Emdin, Ian Langleben, Samantha Lee, Valerie Leung, Larissa Matukas, Anjali Oberai, Kevin L Schwartz, Nick Daneman","doi":"10.1128/jcm.01223-25","DOIUrl":"https://doi.org/10.1128/jcm.01223-25","url":null,"abstract":"<p><p>Antibiograms are challenging to construct in long-term care (LTC) homes in part due to low isolate counts and limited precision. Regional-local antibiograms offer a potential solution by using partial pooling, combining data from both the home and the broader LTC population. We developed regional-local urinary antibiograms and compared this approach to standard antibiograms. This cross-sectional study included urine cultures from LTC residents across Ontario. (i) Standard syndromic combined antibiograms were created for each LTC home with ≥30 total isolates. Homes with <30 isolates used the mean of susceptibility for each drug for the entire province. (ii) Partially pooled regional-local antibiograms were constructed using logistic mixed models with a random intercept for each home to ensure each LTC home could be provided a facility-specific antibiogram. We compared susceptibility and rank order of recommended antibiotics using each method. Among 627 LTC homes, 340 (54.2%) met the ≥30 isolate threshold. Regional-local methods allowed for the development of 627 LTC home-specific antibiograms. These methods narrowed susceptibility estimate ranges compared to standard methods (e.g., trimethoprim-sulfamethoxazole [TMP-SMX]: 57%-77% vs 37%-90%, respectively). A total of 119 (19.0%) homes had at least one antibiotic with over 80% susceptibility using the standard approach; only 11 (1.8%) homes met this threshold with the regional-local antibiogram. The antibiotic with the highest susceptibility varied based on methodology (amoxicillin-clavulanate for standard vs TMP-SMX for regional-local antibiogram). Regional-local antibiograms allow for the creation of facility-specific antibiograms, even among facilities with small isolate counts. This approach may provide more precise antibiotic susceptibility estimates by reducing misleading inter-facility variation.IMPORTANCELocal antibiograms can help inform empiric antibiotic treatment for long-term care residents with urinary tract infections. However, many facilities have too few isolates to create precise susceptibility estimates. A regional-local antibiogram is a novel strategy that uses a weighted approach: it prioritizes local data where available, but increasingly uses regional population-level data for homes with smaller sample sizes to improve statistical precision and reduce misleading inter-facility variation. This regional-local approach allows for the development of facility-specific antibiograms for a greater number of homes compared to traditional methods of developing antibiograms.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0122325"},"PeriodicalIF":5.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photo Quiz: Brown, thick-walled cells with evident septation in a purulent sample from a mason.","authors":"Xiujiao Xia, Zehu Liu","doi":"10.1128/jcm.01552-25","DOIUrl":"https://doi.org/10.1128/jcm.01552-25","url":null,"abstract":"","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0155225"},"PeriodicalIF":5.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic performance of β-(1→3)-D-glucan, two <i>Candida</i> antigen, and five anti-<i>Candida</i> antibody assays in ICU patients with sepsis and high risk for invasive candidiasis: a secondary endpoint of the CandiSep randomized clinical trial.","authors":"Lea Standl, Timo Huber, Frank Bloos, Daniel Thomas-Rüddel, Johannes Träger, Stefan Kluge, Falk Fichtner, Philipp Simon, Klaus Kogelmann, Geraldine de Heer, Sven-Olaf Kuhn, Dominik Jarczak, Johann Motsch, Gunther Hempel, Norbert Weiler, Andreas Weyland, Matthias Drüner, Matthias Gründling, Patrick Meybohm, Daniel Richter, Onnen Moerer, Ulf Günther, Dirk Schädler, Alexander Zarbock, Christian Putensen, Ixchel Castellanos, Oliver Kurzai, Peter Schlattmann, Oliver A Cornely, Michael Bauer, Thomas Lehmann, Giuseppe Valenza, Christian Bogdan, Jürgen Held","doi":"10.1128/jcm.01500-25","DOIUrl":"https://doi.org/10.1128/jcm.01500-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Invasive &lt;i&gt;Candida&lt;/i&gt; infection (ICI) is the most common fungal infection in critically ill patients. This study analyzed the performance of various biomarkers in sera from the CandiSep trial, a randomized, multicenter trial including 342 sepsis patients at high risk for ICI across 18 German intensive care units. ICI and candidemia were diagnosed in 48 (14.0%) and 14 (4.1%) patients, respectively. Sera collected on 2 consecutive days at sepsis onset were analyzed for β-(1→3)-D-glucan (BDG; Fungitell), mannan (Platelia-&lt;i&gt;Candida&lt;/i&gt;-Ag-Plus [Platelia-Mn] and Serion-ELISA-antigen-&lt;i&gt;Candida&lt;/i&gt; [Serion-Mn]), and anti-&lt;i&gt;Candida&lt;/i&gt; antibodies (Platelia-&lt;i&gt;Candida&lt;/i&gt;-Ab-Plus, Serion-ELISA-&lt;i&gt;Candida albicans&lt;/i&gt;-IgA/IgM/IgG, and Virclia-&lt;i&gt;Candida albicans&lt;/i&gt;-germ-tube-antibody-IgG-Monotest). Only antigen levels (BDG, Platelia-Mn, Serion-Mn), but not anti-Candida antibody levels, were significantly elevated in ICI patients. Antigen levels were unaffected by &lt;i&gt;Candida&lt;/i&gt; colonization, while antibody levels were significantly increased. Sensitivity and specificity at the manufacturer's cutoffs were unsatisfactory. Performance improved by adjusting cutoffs: BDG required a 3-fold increase, while all others required lowering. At 80% specificity, sensitivities (95% confidence intervals) for the diagnosis of ICI and candidemia were as follows: BDG (cutoff &gt;280 pg/mL), 46% (31.4-60.8) and 64% (35.1-87.2); Platelia-Mn (cutoff &gt;50 pg/mL), 38% (24.0-52.6) and 64% (35.1-87.2); Serion-Mn (cutoff &gt;0.7 U/mL), 38% (24.0-52.6) and 50% (23.0-77.0), and below 28% and 43% for all antibody assays. Area under the receiver operating characteristic curve comparisons showed no significant differences between antigen assays. Combining biomarkers, either simultaneously or sequentially, offered no diagnostic advantage over single-biomarker use. In conclusion, anti-&lt;i&gt;Candida&lt;/i&gt; antibody assays are likely influenced by colonization and have limited diagnostic utility. Antigen assays offer similar diagnostic value but require cutoff optimization. Combining biomarkers did not enhance diagnostic yield in our cohort.IMPORTANCEOur main findings based on our specific ICU cohort were as follows: (i) only &lt;i&gt;Candida&lt;/i&gt; antigen levels, not anti-&lt;i&gt;Candida&lt;/i&gt; antibody levels, were significantly elevated in ICI and candidemia. (ii) In patients without ICI, Candida colonization was not associated with altered antigen levels, but with elevated antibody levels. (iii) Sensitivity and specificity at the manufacturer's cutoffs were unsatisfactory, and cutoffs should be significantly adjusted. Potential optimal cutoff values are proposed by us. (iv) The evaluated antigen assays demonstrated overall comparable diagnostic performance in this study. (v) Anti-&lt;i&gt;Candida&lt;/i&gt; antibody assays did not provide a meaningful diagnostic contribution. (vi) The combination of biomarkers offered no diagnostic advantage over the use of individual biomarkers, neither simultaneously nor sequential","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0150025"},"PeriodicalIF":5.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Test performance of a commercial cryptococcal antigen lateral flow assay: a retrospective and prospective study at five Canadian sites.","authors":"Catherine A Hogan, LingHui David Su, Jonathan Laley, Erin Carruthers, Adrienne Wong, Susan Roman, Kulvinder Mannan, Pamela Kibsey, Balbir Jaswal, Bing Wang, Krysta Grant, Caroline Sheitoyan-Pesant, Navdeep Chahil, Marthe K Charles, Vincent Tang, Constance Byrne, David M Goldfarb, Muhammad G Morshed","doi":"10.1128/jcm.01438-25","DOIUrl":"https://doi.org/10.1128/jcm.01438-25","url":null,"abstract":"<p><p>Cryptococcal antigen (CrAg) lateral flow assay (LFA) enables the rapid and sensitive detection of cryptococcal infection. The FungiXpert CrAg LFA is a Health Canada-licensed product that currently lacks evaluation in the North American setting. This retrospective and prospective study across five Canadian laboratories aimed to evaluate the FungiXpert CrAg LFA compared to the IMMY CrAg LFA for serum and cerebrospinal fluid (CSF) samples. Positive percent agreement (PPA) and negative percent agreement (NPA), precision, and cross-reactivity were assessed. A retrospective data review was performed for demographics, clinical data, and additional diagnostic testing results. A total of 141 serum samples and 93 CSF samples from 192 individuals were included. In the overall retrospective cohort, the FungiXpert CrAg LFA demonstrated qualitative detection PPA of 90.2% (95% confidence interval [95% CI], 87.3%-93.1%), and NPA of 100% (95% CI, 97.7%-100%). By sample type, the CSF PPA was 93.9% (95% CI, 79.8%-99.3%), and the serum PPA was 90.7% (95% CI, 79.7%-96.9%). The prospective cohort consisted of 58 samples, including two serum samples that were positive; of these, one was a low titer (1:1) and missed by FungiXpert. Both assays showed cross-reactivity with <i>Trichosporon asahii</i>. Inter-assay precision evaluation highlighted substantial variability in the FungiXpert CrAg LFA serum testing. These findings suggest similar performance of the FungiXpert CrAg LFA on CSF samples, but lower sensitivity on serum samples and greater lot-to-lot variability compared to IMMY CrAg LFA that should be considered in clinical implementation decision-making. In this Canadian multicenter study, the FungiXpert CrAg LFA demonstrated similar performance on CSF samples but lower sensitivity on serum samples compared to the IMMY CrAg LFA.IMPORTANCEThis multicenter Canadian evaluation provides the first North American performance data for the Health Canada-licensed FungiXpert cryptococcal antigen lateral flow assay. While performance on cerebrospinal fluid was comparable to the reference IMMY assay, reduced sensitivity for low-titer serum samples and greater inter-assay variability highlight important considerations for clinical implementation and assay selection.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0143825"},"PeriodicalIF":5.4,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of standard and modified two-tiered testing algorithms using well-characterized early Lyme disease samples.","authors":"Elizabeth J Horn, Barry Menefee, Anna M Schotthoefer, George Dempsey, Matt McArdle, Allison F Weber, Cathy De Luca, Bobbi S Pritt, John A Branda","doi":"10.1128/jcm.01187-25","DOIUrl":"10.1128/jcm.01187-25","url":null,"abstract":"<p><p>Current laboratory testing for Lyme disease (LD) relies on serology. We evaluated the performance of standard two-tiered testing (STTT) and modified two-tiered testing (MTTT) algorithms using samples obtained from well-characterized patients with early LD in the U.S. East Coast and Upper Midwest. Participants with signs and symptoms of early LD (cases) and controls were enrolled by Lyme Disease Biobank. We compared the performance of four FDA-cleared STTT or MTTT algorithms using serum samples from 251 participants (107 cases, 69 with a convalescent draw; 144 endemic controls). At the initial blood draw, algorithm sensitivity ranged from 22% to 36%, with specificity ranging from 98% to 100%. MTTT algorithms showed higher sensitivity compared with STTT algorithms (<i>P</i> ≤ 0.05). One STTT algorithm was less sensitive than the other (<i>P</i> = 0.035), and there was no significant difference in sensitivity between MTTT algorithms. There was also discordance between algorithms; only 22 of the 45 samples classified as laboratory confirmed by Lyme Disease Biobank testing were positive using all algorithms evaluated. Likelihood of positive two-tiered serology among cases with a suspected erythema migrans (EM) skin lesion increased with longer lesion duration and/or when presenting with >1 constitutional symptom. Participants with suspected EM without constitutional symptoms were unlikely to test positive by any algorithm evaluated. Testing convalescent samples did not improve LD detection, and seroconversion was rare. While MTTT confirmed more early LD cases than STTT, all two-tiered algorithms evaluated were insensitive in this population. Novel diagnostics that improve laboratory confirmation for early LD are urgently needed.</p><p><strong>Importance: </strong>This study confirms that two-tiered serologic testing algorithms are insensitive in early Lyme disease, particularly within the first 2 weeks after symptom onset or when erythema migrans is not accompanied by constitutional symptoms. It also demonstrates that seroconversion is rare after antibiotic treatment. These results highlight the need for novel diagnostics for early Lyme disease that do not rely on serologic testing.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0118725"},"PeriodicalIF":5.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point-Counterpoint: Should MRSA nares testing be used as a tool for vancomycin de-escalation outside of pneumonia?","authors":"Dan Ilges, Drew T Dickinson, Jennifer M Bosquez, Erin H Graf","doi":"10.1128/jcm.01309-25","DOIUrl":"https://doi.org/10.1128/jcm.01309-25","url":null,"abstract":"<p><p>Vancomycin is broadly used to treat gram-positive infections in both inpatient and outpatient settings. Its use is primarily for the treatment of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), which is a common cause of pneumonia, skin and soft tissue infections, and bloodstream infections. Vancomycin therapy requires close clinical monitoring to maintain therapeutic efficacy and, importantly, patient safety. Vancomycin use is associated with acute kidney injury in up to 20% of cases, a number that can be driven down by pharmacokinetic dosing protocols. However, the best mitigation against adverse outcomes associated with vancomycin is to ensure it is only used when needed and rapidly de-escalated when not. As such, many stewardship programs, who are tasked with the safe and effective use of antimicrobial agents, have focused on optimizing vancomycin use. There is a strong correlation with MRSA colonization and infection, and a negative MRSA nares screen has a good negative predictive value for MRSA pneumonia (although this association is less well documented for other infections). As such, detection of MRSA in nares swabs, by nucleic acid amplification tests (NAATs) or culture, is a logical tool for stewarding vancomycin. However, the application of MRSA screening tests as MRSA diagnostics is complex, as these tests are cleared by the U.S. Food and Drug Administration for the detection of MRSA colonization, and not for therapeutic decision making. In this issue of the Journal of Clinical Microbiology, the issue of MRSA nares tests is debated by a clinical pharmacy team and the laboratory. The authors review the clinical evidence and regulatory background in which an MRSA nares NAAT may be used to inform treatment decisions.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0130925"},"PeriodicalIF":5.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}