Open Forum Infectious Diseases最新文献

{"title":"Hepatitis E Virus Infection in Vietnamese Pregnant Women with Hepatitis B: Prevalence and Clinical Outcomes.","authors":"Le Thi Hong Van, Hoang Van Tong, Bui Thanh Thuyet, Bui Lan Anh, Le Chi Cao, Do Thu Trang, Nghiem Xuan Hoan, Trinh Xuan Huy, Ngo Thu Hang, Can Van Mao, Tran Thi Thanh Huyen, Nguyen Linh Toan, Le Huu Song, C Thomas Bock, Heiner Wedemeyer, Thirumalaisamy P Velavan, Bui Tien Sy","doi":"10.1093/ofid/ofaf081","DOIUrl":"10.1093/ofid/ofaf081","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis E virus (HEV) infection during pregnancy is associated with obstetric complications and adverse maternal and neonatal outcomes. This study aimed to determine the seroprevalence of HEV and RNA positivity in both healthy pregnant women and women coinfected with hepatitis B virus (HBV).</p><p><strong>Methods: </strong>A cross-sectional study was conducted involving 528 pregnant women (278 with and 250 without hepatitis B surface antigen [HBsAg]) in their third trimester. Anti-HEV specific immunoglobulin (Ig) G and IgM antibodies were tested for using enzyme-linked immunosorbent assay, while HEV RNA was detected by means of nested polymerase chain reaction. The status of anti-HEV antibodies was analyzed regarding pregnancy outcomes and the risks of obstetric complications.</p><p><strong>Results: </strong>The results indicated that 24% of participants (127 of 528) tested positive for anti-HEV IgG, while 2.5% (13 of 528) showed detectable anti-HEV IgM. Among HBV-positive women, 26% (55 of 250) had anti-HEV IgG, comparable to 22% (61 of 278) in HBV-negative controls. Notably, 28% (140 of 501) of cord blood samples were positive for anti-HEV IgG. No cases of HEV RNA were detected. The prevalence of anti-HEV IgG increased with maternal age and was associated with higher infant birth weights. Anti-HEV IgM positivity was associated with an increased risk of neonatal infections (odds ratio, 20.6; <i>P</i> = .05). Among HBsAg-positive women, those with anti-HEV IgG (26%) had higher gestational age at delivery and higher infant birth weights but lower platelet counts and prothrombin times (<i>P</i> < .05).</p><p><strong>Conclusions: </strong>These findings highlight the endemic nature of HEV in Vietnam and underscore the potential risks of coinfection with HBV during pregnancy, which may lead to adverse obstetric outcomes.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 3","pages":"ofaf081"},"PeriodicalIF":3.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness of 3 Types of Acellular Pertussis Vaccines Among Children Aged 3 Months-16 Years in Lu'an, China: A Matched Case-Control Study.","authors":"Wei Qin, Bingxin Ma, Huan Zhang, Yao Wang, Fan Pan, Yafei Chen, Yu Zhou, Yongyu Liu, Liguo Ma, Changjun Zhao, Yongjie Tian","doi":"10.1093/ofid/ofaf082","DOIUrl":"10.1093/ofid/ofaf082","url":null,"abstract":"<p><strong>Background: </strong>The real-world vaccine effectiveness (VE) of the diphtheria, tetanus, and acellular pertussis (DTaP), DTaP-<i>Haemophilus influenzae</i> type b (Hib), and DTaP-inactivated polio (IPV)/Hib vaccines has not been thoroughly evaluated in China. Additionally, there are limited data on the VE of acellular pertussis-containing vaccines (aPVs) when used interchangeably.</p><p><strong>Methods: </strong>We conducted a matched case-control study to estimate the VE of aPVs against polymerase chain reaction-confirmed pertussis infection in Lu'an in 2024. A conditional logistic regression model was used to compare the odds ratios (ORs) of vaccination between cases and controls. VE was calculated as [(1 - adjusted OR) × 100%], and 95% confidence intervals (CIs) were computed around the estimates.</p><p><strong>Results: </strong>A total of 1936 children aged 3 months to 16 years were included in the study. The overall VE was 77.3% (95% CI, 35.2%-92.1%). The VE for fully vaccinated children was 88.4% (95% CI, 57.3%-96.8%), while the VE for partially vaccinated children was 77.4% (95% CI, 35.5%-92.1%). The VE of DTaP, DTaP-Hib, and DTaP-IPV/Hib was 75.8% (95% CI, 29.7%-91.7%), 83.2% (95% CI, 47.8%-94.6%), and 79.8% (95% CI, 36.5%-93.6%), respectively. Compared with mixed vaccination (65.3%.), the incremental VE of DTaP, DTaP-Hib, and DTaP-IPV/Hib was 31.0% (95% CI, 1.0%-51.9%), 52.9% (95% CI, 19.1%-72.6%), and 41.1% (95% CI, -18.7% to 71.8%), respectively. We observed a decline in VE over time, decreasing from 76.5% (95% CI, 33.0%-91.7%) within the first 2 years to -5.5% (95% CI, -495.2% to 81.3%) after 6 years or more.</p><p><strong>Conclusions: </strong>All aPVs provide significant protection against pertussis infection, although this protection wanes over time. The VE appears to decrease materially if these vaccines are administered alternately in an individual's routine immunization schedule.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 2","pages":"ofaf082"},"PeriodicalIF":3.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Tuberculosis Infectiousness of Persons Identified Through Active and Passive Case-finding in a High-burden Setting.","authors":"Lilian N Njagi, Khai Hoan Tram, Jerry S Zifodya, Sharmila Paul, Jennifer M Ross, Wilfred Murithi, Zipporah Mwongera, Richard Kiplimo, Jane R Ong'ang'o, Kevin P Fennelly, Thomas R Hawn, Videlis Nduba, David J Horne","doi":"10.1093/ofid/ofaf077","DOIUrl":"10.1093/ofid/ofaf077","url":null,"abstract":"<p><strong>Background: </strong>The role of active case-finding (ACF) in improving tuberculosis (TB) prevention and care depends on the infectiousness of persons with undiagnosed TB and the accuracy of screening strategies. To compare undiagnosed community dwellers to persons presenting for healthcare, we evaluated clinicodemographic and microbiologic characteristics, cough aerosol culture (CAC) status, and household contact (HHC) QuantiFERON-Plus (QFT) status by case-finding approach in adults with pulmonary TB.</p><p><strong>Methods: </strong>We enrolled 388 Kenyan adults with GeneXpert (excluding trace) and/or culture-confirmed, untreated TB through healthcare presentation (passive case-finding [PCF]; 87%) or ACF (community-based prevalence survey). Interventions included cough aerosol sampling and HHC QFT testing. We performed mixed-effect logistic regression to predict transmission, clustered on index participants.</p><p><strong>Results: </strong>World Health Organization-recommended screening symptoms (W4SS) were more common in the PCF cohort (99% vs 73%, <i>P</i> < .001). Traditional makers of infectiousness were less frequent in the ACF cohort. Higher symptom burden (number of reported World Health Organization-recommended 4-symptom screen) associated with higher bacillary burden (lower GeneXpert Ct) (estimate -0.55; 95% confidence interval [CI], -.98 to -.13; <i>P</i> = .01). Among 263 participants with CAC, 21% were CAC-positive, none of whom enrolled through ACF. Among 270 HHCs, QFT positivity differed by index CAC status (89% vs 56% in HHCs of CAC-positive and negative participants, respectively; <i>P</i> < .001) but not by traditional infectiousness makers or case-finding approach. Index CAC-positive status (adjusted odds ratio [aOR], 11.2; CI, 2.2-58.3), HIV-positive status (aOR, 0.1; CI, .0-.6), and HHCs age (aOR, 1.04; CI, 1.01-1.08), independently predicted HHC QFT positivity.</p><p><strong>Conclusions: </strong>Our findings suggest that ACF may detect a smaller proportion of CAC-positive persons with TB than PCF.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 3","pages":"ofaf077"},"PeriodicalIF":3.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Mycobacterium bovis</i> Infections Following Intravesical Bacillus Calmette-Guérin Instillation for Bladder Cancer in Western Australia: A 22-Year Retrospective Review.","authors":"Usha Manickavasagar, Henco Nel, Jason Seet, Liana Varrone, Terillee Keehner, Rebecca McCann, Rosie Barnes, Angela Jacques, Penelope Clohessy","doi":"10.1093/ofid/ofaf070","DOIUrl":"10.1093/ofid/ofaf070","url":null,"abstract":"<p><p><i>Mycobacterium bovis</i> bacillus Calmette-Guérin (BCG) infection following intravesical BCG instillation is a rare complication of therapy that is associated with significant morbidity and mortality. We conducted a multicenter retrospective review of microbiologically confirmed <i>M.bovis</i> BCG infections in Western Australia over 22 years. Thirty-three patients were included in our study. All patients were male with a median age of 72 years. Localized infections accounted for 22/33 cases while disseminated infections accounted for 11/33 cases. The majority (n = 21) of positive isolates were cultured from urine specimens, followed by tissue and blood. The median time between first BCG instillation and infection was 7.5 months (95% CI, 3.5-11.5). The median duration of antimycobacterial therapy for localized infections was 6 months (95% CI, 4.1-7.9) as compared with 9 months (95% CI, 7.9-10.1) for disseminated infections (<i>P</i> = .039). The attributed mortality was 14.3%. <i>M.bovis</i> BCG infections have diverse clinical presentations and clinicians must have a high index of suspicion when assessing patients with a history of intravesical BCG instillation.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 2","pages":"ofaf070"},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuing the Chat: How Can We Improve the Performance of an Artificial Intelligence Chatbot in Answering Clinical Infectious Diseases Pharmacotherapy Questions?","authors":"Matthew Chung Yi Koh, Nares Smitasin, Paul Anantharajah Tambyah, Jinghao Nicholas Ngiam","doi":"10.1093/ofid/ofaf073","DOIUrl":"10.1093/ofid/ofaf073","url":null,"abstract":"","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 2","pages":"ofaf073"},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Comparison of COVID Waves 2-5. An Inpatient Retrospective Comparative Analysis From Karachi, Pakistan.","authors":"Muneeba Ahsan Sayeed, Elisha Shalim, Shaiza Farman, Fizza Farooqui, Beenish Syed, Ishfaque Ahmed, Anika Iqbal, Aneel Kumar, Raniyah Akhter, Furkan Hyder, Hasan Ali Shah, Adeel Hussain, Sarwat Rasheed, Saba Afshan, Rizwana Salik Nukrich, Madiha Raza, Haseeb U Rehman, Abdul Razzaque Memon, Abdul Wahid Rajput, Muhammad Saeed Quraishy","doi":"10.1093/ofid/ofaf072","DOIUrl":"10.1093/ofid/ofaf072","url":null,"abstract":"<p><strong>Background: </strong>Each coronavirus disease 2019 (COVID-19) wave is unique in its clinical presentation and outcome. In this study, we compared the clinical characteristics and outcomes of COVID waves 2-5 in inpatient settings.</p><p><strong>Methods: </strong>A retrospective study was conducted at the Sindh Infectious Diseases Hospital and Research Center on adult patients who were admitted with a positive COVID polymerase chain reaction from July 2020 to March 2022. SPSS 26 was used to analyze the data.</p><p><strong>Results: </strong>A total of 3190 COVID-19 patients were admitted. Wave 2 had the highest percentage of discharges compared with mortality (81%; <i>P</i> = .0001). Cytokine release syndrome was most common in wave 3 (32.7%; <i>P</i> = .0001). Severe COVID on admission was predominant in wave 4 (79.4%; <i>P</i> = .0001), with the highest rates of intubation (27.1%; <i>P</i> = .0001), septic shock (24.3%; <i>P</i> = .0001), and disease progression (50.8%; <i>P</i> = .0001). In wave 5, the majority were elderly (median age, 68 years) and had mild COVID (22.4%; <i>P</i> = .0001), most had comorbidities (84.6%; <i>P</i> = .0001), and the ratio of acute kidney injury was high (29.2%; <i>P</i> = .0001). Mortality was lowest in wave 2 (18.9%; <i>P</i> = .0001) and highest in wave 4 (42.5%; <i>P</i> = .0001; odds ratio, 3.18; 95% CI, 2.6-3.8; compared with wave 2).</p><p><strong>Conclusions: </strong>Each wave had some unique characteristics compared with other waves, with wave 4, driven by the Delta variant, being the deadliest one in terms of disease severity and outcomes.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 3","pages":"ofaf072"},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Interpretation of Positive Metagenomic Next-Generation Sequencing Reports on the Infection Diagnosis in Patients With Hematological Disorders.","authors":"Chunhui Xu, Yuyan Shen, Shulian Chen, Teng Liu, Xin Chen, Yuetian Yu, Li Liu, Runzhi Ma, Lining Zhang, Xin Liu, Lukun Zhou, Guoqing Zhu, Sizhou Feng","doi":"10.1093/ofid/ofaf076","DOIUrl":"10.1093/ofid/ofaf076","url":null,"abstract":"<p><strong>Background: </strong>Metagenomic next-generation sequencing (mNGS) has become a crucial diagnostic tool for infectious diseases in patients with hematological disorders. However, despite the abundant microbial information provided by positive mNGS reports, interpreting these results remains challenging due to the lack of standardized criteria.</p><p><strong>Methods: </strong>We surveyed 92 clinicians to identify common challenges in understanding mNGS reports. Microbiologists then provided additional \"report interpretation cards\" (RICs) for positive mNGS results alongside original reports. The aim of using RICs was to determine whether each detected microorganism was likely cause of infection. After a 3-month period, a panel of clinical experts retrospectively reviewed 281 cases, involving 728 detected microorganisms, to assess RIC accuracy.</p><p><strong>Results: </strong>In total, 82.6% of clinicians (76 of 92) experienced difficulties in interpreting mNGS reports. After receiving RICs, 97.8% of clinicians (90 of 92) reported satisfaction. The overall concordance rates between interpretation and adjudication in the 281 cases was 79.0% (222 of 281). In 203 cases in which multiple microorganisms were detected, 37.9% (77 of 203) and 37.4% (76 of 203) were interpreted and adjudicated as mixed infections. Among the 728 microorganisms, interpretation and adjudication revealed concordance rates of 93.9% (154 of 164), 95.7% (88 of 92), and 72.3% (339 of 469) for bacterial, fungal, and viral infections, respectively. In 68.7% of the cases (193 of 281), mNGS positively influenced pathogen diagnosis.</p><p><strong>Conclusions: </strong>Not all microorganisms detected by mNGS are responsible for infection, and appropriate interpretation is essential. The provision of interpretations by microbiologists aids clinicians in accurately using mNGS for infection diagnosis.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 2","pages":"ofaf076"},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Big Data Bayesian Truths: No Vancomycin Trough Concentration Target Is Sufficiently Precise for Safety or Efficacy.","authors":"Justin Shiau, Sharmeen Roy, Paul Sabourenkov, Marc H Scheetz","doi":"10.1093/ofid/ofaf041","DOIUrl":"10.1093/ofid/ofaf041","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic drug monitoring is standard of care for vancomycin because of the known efficacy and safety exposure window (ie, area under the concentration-time curve [AUC] of 400-600 mg × 24 hours/L). Despite guideline recommendations, AUCs are infrequently calculated because of the perceived adequacy of trough (Cmin) concentrations. Yet, the percentage of real-world patients with goal measured vancomycin trough concentrations that achieve target vancomycin AUC remains unknown.</p><p><strong>Methods: </strong>A large cohort of internationally represented adult patients treated with vancomycin in 2021 and 2022 and therapeutic drug monitoring performed had data anonymized via an electronic clearinghouse at DoseMe. Unique patients, dosing events, and measured Cmin were identified. Patient-individualized AUC was calculated using a Bayesian method with 4 validated models. For each dosing event, Cmin and AUC pairs were compared and categorized as \"low,\" \"target,\" and \"high\" using the therapeutic ranges for Cmin of 15-20 mg/L and AUC of 400-600 mg × 24 hours/L.</p><p><strong>Results: </strong>In 2022, 17,711 adult patients from the European Union (4.9%), Australia (4.0%), and the United States (91.1%) had 26 769 measured trough levels obtained. Categorical disagreement between Cmin and AUC was 34.3%, with most disagreement (7959 Cmin levels, 30%) occurring with low Cmin but target AUC. Only 23% of paired Cmin and AUC were within range. AUC was variable for all trough categories (ie, low, target, and high).</p><p><strong>Conclusions: </strong>These findings support AUC therapeutic drug monitoring and challenge Cmin as an adequate vancomycin AUC proxy. Because no trough concentration or range was sufficiently precise to ensure AUC targets, we suggest direct calculation of AUC.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 3","pages":"ofaf041"},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: \"Continuing the Chat: How Can We Improve the Performance of an Artificial Intelligence Chatbot in Answering Clinical Infectious Diseases Pharmacotherapy Questions?\"","authors":"Wesley D Kufel, Conan MacDougall, Elizabeth W Covington, Jason C Gallagher, Robert W Seabury, Jeffrey M Steele","doi":"10.1093/ofid/ofaf074","DOIUrl":"10.1093/ofid/ofaf074","url":null,"abstract":"","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 2","pages":"ofaf074"},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Chart Biopsy to Liquid Biopsy: Evaluating the Diagnostic Yield and Clinical Impact of Plasma Microbial Cell-Free DNA Next-Generation Sequencing in the Management of Fever of Unknown Origin.","authors":"Nischal Ranganath, Bismarck Bisono Garcia, James Vaillant, Silpita Katragadda, Melissa Kerkelis, Omar Abu Saleh, Madiha Fida","doi":"10.1093/ofid/ofaf038","DOIUrl":"10.1093/ofid/ofaf038","url":null,"abstract":"<p><strong>Background: </strong>The underlying cause of fever of unknown origin (FUO) remains unidentified in up to 51% of cases despite systematic evaluation. Microbial cell-free DNA next-generation sequencing (mcfDNA-NGS) offers an agnostic, noninvasive approach to pathogen identification, but the utility and clinical impact of this assay in FUO remain unknown.</p><p><strong>Methods: </strong>This retrospective cohort study evaluated adult patients referred for FUO evaluation at a tertiary medical center between November 2019 and November 2023. Patients underwent both standard microbiologic testing (ST) and mcfDNA-NGS. Diagnostic impact was assessed in 4 domains: new diagnoses, earlier time to diagnosis, avoidance of invasive procedures, and non-hypothesis-driven diagnoses. Logistic regression was used to identify predictors of positive mcfDNA-NGS testing.</p><p><strong>Results: </strong>Among 176 patients, mcfDNA-NGS was positive in 44.3%, with 49% of these cases considered clinically significant. Infectious cause of FUO was identified in 39% of patients, noninfectious in 35%, and unknown in 26%. mcfDNA-NGS contributed to a positive diagnostic impact in 30% of cases, mainly by earlier diagnosis (16%) and potential for avoidance of invasive procedures (10%). Positive mcfDNA-NGS was significantly associated with higher Charlson comorbidity index score (odds ratio [OR], 1.22; <i>P</i> < .001) and white blood cell (WBC) count ≤4.5 × 10⁹ cells/L (OR, 8.61; <i>P</i> < .001). Conversely, FUO without localization was associated with a decreased likelihood of positive mcfNDA testing (OR, 0.18; <i>P</i> < .001).</p><p><strong>Conclusions: </strong>mcfDNA-NGS effectively complements ST in diagnosing FUO, providing earlier detection and minimizing invasive testing. Clinical predictors such as high comorbidity and low WBC count may guide the optimal use of mcfDNA-NGS in FUO. Prospective evaluation of optimal timing and use of mcfDNA-NGS and cost-benefit analysis in FUO is needed.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 2","pages":"ofaf038"},"PeriodicalIF":3.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}