BACKGROUNDAccurate non-sputum tests are essential for improving tuberculosis (TB) detection. We report the first evaluation of the Xpert TB/LTBI assay (research-use-only, Cepheid, USA), which detects nine Mycobacterium tuberculosis antigen-stimulated mRNA targets from blood.METHODSWe enrolled individuals ≥12 years with presumptive TB from clinics in Uganda and Vietnam. All participants underwent sputum- (liquid culture; Xpert MTB/RIF Ultra) and blood-based (Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]) testing. Participants were classified as having active TB (positive sputum results), latent TB infection (LTBI; positive QFT-Plus with negative sputum results), or no TB infection. Diagnostic accuracy for active TB (primary analysis) and of a two-step algorithm that first predicted TB infection (active TB or LTBI) and then distinguished active TB from LTBI was assessed using logistic regression and receiver operating characteristic analysis.RESULTSAmong 214 participants included, 56.5% were male, 9.3% were living with HIV, 29.0% had active TB, and 31.8% had LTBI. Xpert TB/LTBI area under the curve (AUC) was 0.92 (95% CI 0.88-0.96) for identifying active TB, and sensitivity was 93.5% (95% CI 84.6-97.5) and specificity 76.3% (95% CI 69.0-82.4) at a cut-point that achieved ≥90% sensitivity. In the two-step algorithm, Xpert TB/LTBI had high accuracy for identifying TB infection in the first step, but accuracy was lower for distinguishing active TB from LTBI in the second step.CONCLUSIONSXpert TB/LTBI exceeded World Health Organization (WHO)-recommended minimum accuracy targets for a TB screening test. However, further refinement is needed to improve its ability to distinguish active TB from LTBI.
背景：准确的非痰液检测对于提高结核病的检出率至关重要。我们报告了对Xpert TB/LTBI检测（仅供研究使用，造父变星，美国）的首次评估，该检测从血液中检测出9个结核分枝杆菌抗原刺激的mRNA靶点。方法：我们从乌干达和越南的诊所招募了年龄≥12岁的推定结核病患者。所有参与者都进行了痰液（液体培养；Xpert MTB/RIF Ultra）和血液（Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]）检测。参与者被分类为活动性结核（痰液结果阳性）、潜伏性结核感染（LTBI； QFT-Plus阳性，痰液结果阴性）或无结核感染。对活动性结核病的诊断准确性（初步分析）以及首先预测结核病感染（活动性结核病或LTBI），然后将活动性结核病与LTBI区分开来的两步算法，使用逻辑回归和患者工作特征分析进行了评估。结果在214名参与者中，56.5%为男性，9.3%为艾滋病毒携带者，29.0%为活动性结核病，31.8%为LTBI。Xpert TB/LTBI识别活动性TB的曲线下面积（AUC）为0.92 (95% CI 0.88-0.96)，在达到≥90%灵敏度的切点上，灵敏度为93.5% (95% CI 84.6-97.5)，特异性为76.3% （95% CI 69.0-82.4）。在两步算法中，Xpert TB/LTBI在第一步识别结核感染的准确率较高，但在第二步区分活动性结核和LTBI的准确率较低。结论专家结核病/LTBI超过了世界卫生组织（WHO）推荐的结核病筛查试验的最低准确性目标。然而，需要进一步改进以提高其区分活动性结核和LTBI的能力。
{"title":"Evaluating the Cepheid Xpert TB/LTBI research-use-only assay for detection of active and latent Mycobacterium tuberculosis infection.","authors":"Brittney Sweetser,Hoang Nguyen,Hai Dang,David Katumba,Tessa Mochizuki,Qiao Wang,Mangeni Wilson,Ha Phan,Patrick Phillips,Seda Yerlikaya,Payam Nahid,Claudia M Denkinger,Adithya Cattamanchi,William Worodria, ","doi":"10.1093/cid/ciag005","DOIUrl":"https://doi.org/10.1093/cid/ciag005","url":null,"abstract":"BACKGROUNDAccurate non-sputum tests are essential for improving tuberculosis (TB) detection. We report the first evaluation of the Xpert TB/LTBI assay (research-use-only, Cepheid, USA), which detects nine Mycobacterium tuberculosis antigen-stimulated mRNA targets from blood.METHODSWe enrolled individuals ≥12 years with presumptive TB from clinics in Uganda and Vietnam. All participants underwent sputum- (liquid culture; Xpert MTB/RIF Ultra) and blood-based (Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]) testing. Participants were classified as having active TB (positive sputum results), latent TB infection (LTBI; positive QFT-Plus with negative sputum results), or no TB infection. Diagnostic accuracy for active TB (primary analysis) and of a two-step algorithm that first predicted TB infection (active TB or LTBI) and then distinguished active TB from LTBI was assessed using logistic regression and receiver operating characteristic analysis.RESULTSAmong 214 participants included, 56.5% were male, 9.3% were living with HIV, 29.0% had active TB, and 31.8% had LTBI. Xpert TB/LTBI area under the curve (AUC) was 0.92 (95% CI 0.88-0.96) for identifying active TB, and sensitivity was 93.5% (95% CI 84.6-97.5) and specificity 76.3% (95% CI 69.0-82.4) at a cut-point that achieved ≥90% sensitivity. In the two-step algorithm, Xpert TB/LTBI had high accuracy for identifying TB infection in the first step, but accuracy was lower for distinguishing active TB from LTBI in the second step.CONCLUSIONSXpert TB/LTBI exceeded World Health Organization (WHO)-recommended minimum accuracy targets for a TB screening test. However, further refinement is needed to improve its ability to distinguish active TB from LTBI.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"39 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005024","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}
Patricia Winokur,Oyeniyi Diya,David Fitz-Patrick,Michael Dever,Juleen Gayed,Stephen Lockhart,Xia Xu,Ying Zhang,Vishva Bangad,L Tyler Wadsworth,Kevin Cannon,Jose F Cardona,Lisa Usdan,John Ginis,Federico J Mensa,Jing Zou,Xuping Xie,Claire Lu,Sandra Buitrago,Ingrid L Scully,David Cooper,Kenneth Koury,Kathrin U Jansen,Ӧzlem Türeci,Uğur Şahin,Kena A Swanson,William C Gruber,Nicholas Kitchin
BACKGROUNDEmergence of SARS-CoV-2 sublineages warrants the use of sequence-adapted vaccines to provide protection against COVID-19.METHODSIn this phase 3 trial, adults 18‒55 years old who had previously received three 30-μg doses of BNT162b2 vaccine were randomized to receive a 60- or 30-μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60-μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron-BA.1, BA.4, and BA.5 subvariants and ancestral strain.RESULTSAmong the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60-µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs]: 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs: 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n=30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5.CONCLUSIONSBivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains.NCT04955626.
{"title":"Safety and Immunogenicity of a Fourth Dose of Omicron-BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18‒55 Years Old.","authors":"Patricia Winokur,Oyeniyi Diya,David Fitz-Patrick,Michael Dever,Juleen Gayed,Stephen Lockhart,Xia Xu,Ying Zhang,Vishva Bangad,L Tyler Wadsworth,Kevin Cannon,Jose F Cardona,Lisa Usdan,John Ginis,Federico J Mensa,Jing Zou,Xuping Xie,Claire Lu,Sandra Buitrago,Ingrid L Scully,David Cooper,Kenneth Koury,Kathrin U Jansen,Ӧzlem Türeci,Uğur Şahin,Kena A Swanson,William C Gruber,Nicholas Kitchin","doi":"10.1093/cid/ciag026","DOIUrl":"https://doi.org/10.1093/cid/ciag026","url":null,"abstract":"BACKGROUNDEmergence of SARS-CoV-2 sublineages warrants the use of sequence-adapted vaccines to provide protection against COVID-19.METHODSIn this phase 3 trial, adults 18‒55 years old who had previously received three 30-μg doses of BNT162b2 vaccine were randomized to receive a 60- or 30-μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60-μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron-BA.1, BA.4, and BA.5 subvariants and ancestral strain.RESULTSAmong the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60-µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs]: 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs: 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n=30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5.CONCLUSIONSBivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains.NCT04955626.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"49 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005025","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}
Adriana R Marques,Siu-Ping Ng,Julie E McCarthy,Sam R Telford,Kenneth Dardick,Gary P Wormser,Luis A Marcos,Rafal Tokarz,Carla Williams,Melissa Law,Joshua Norville,Maureen Lundt,Tanja Petnicki-Ocwieja,Carol Scavarda,Donna McKenna,Heidi K Goethert,Allyson Mateja,Dean Follman,Mark W Eshoo,Linden T Hu
BACKGROUNDSome patients report non-specific symptoms after antibiotic therapy for Lyme disease (LD), raising questions about ongoing infection, despite no compelling evidence. We investigated whether xenodiagnosis could detect Borrelia burgdorferi in such patients, and if positive results correlated with symptoms.METHODSParticipants were adults who completed antibiotic treatment for LD 3-12 months earlier (post-therapy, n=40) or had persistent symptoms for ≥ 12 months after treatment, (post-treatment LD symptoms [PTLDS], n=20). Controls included one patient with erythema migrans (EM), one patient with untreated Lyme arthritis (LA), and 9 healthy volunteers (HV). Participants had 25-30 larval Ixodes scapularis ticks placed; ticks were collected 3-6 days later and tested for B. burgdorferi. The primary analysis evaluated if B. burgdorferi detection by xenodiagnosis was associated with persistence of symptoms in patients during the first year after treatment. This trial is registered with ClinicalTrials.gov, NCT02446626.RESULTSRecovered ticks included 402 from post-therapy, 314 from PTLDS, 30 from the EM patient, 11 from the LA patient, and 80 from HV. All ticks tested negative for B. burgdorferi except for 1 tick from a recovered patient. An unplanned interim analysis led to the early termination of the study for futility.CONCLUSIONXenodiagnosis with larval I. scapularis ticks showed no evidence of B. burgdorferi in most patients after treatment, irrespective of symptoms. This may be due to absence of bacteria or to the low sensitivity of the technique in humans. This method is unlikely to detect persistent B. burgdorferi infection in humans and further research on the use of xenodiagnosis is unwarranted.
{"title":"Xenodiagnosis to search for Borrelia burgdorferi after antibiotic treatment of Lyme disease: a prospective cohort study.","authors":"Adriana R Marques,Siu-Ping Ng,Julie E McCarthy,Sam R Telford,Kenneth Dardick,Gary P Wormser,Luis A Marcos,Rafal Tokarz,Carla Williams,Melissa Law,Joshua Norville,Maureen Lundt,Tanja Petnicki-Ocwieja,Carol Scavarda,Donna McKenna,Heidi K Goethert,Allyson Mateja,Dean Follman,Mark W Eshoo,Linden T Hu","doi":"10.1093/cid/ciag031","DOIUrl":"https://doi.org/10.1093/cid/ciag031","url":null,"abstract":"BACKGROUNDSome patients report non-specific symptoms after antibiotic therapy for Lyme disease (LD), raising questions about ongoing infection, despite no compelling evidence. We investigated whether xenodiagnosis could detect Borrelia burgdorferi in such patients, and if positive results correlated with symptoms.METHODSParticipants were adults who completed antibiotic treatment for LD 3-12 months earlier (post-therapy, n=40) or had persistent symptoms for ≥ 12 months after treatment, (post-treatment LD symptoms [PTLDS], n=20). Controls included one patient with erythema migrans (EM), one patient with untreated Lyme arthritis (LA), and 9 healthy volunteers (HV). Participants had 25-30 larval Ixodes scapularis ticks placed; ticks were collected 3-6 days later and tested for B. burgdorferi. The primary analysis evaluated if B. burgdorferi detection by xenodiagnosis was associated with persistence of symptoms in patients during the first year after treatment. This trial is registered with ClinicalTrials.gov, NCT02446626.RESULTSRecovered ticks included 402 from post-therapy, 314 from PTLDS, 30 from the EM patient, 11 from the LA patient, and 80 from HV. All ticks tested negative for B. burgdorferi except for 1 tick from a recovered patient. An unplanned interim analysis led to the early termination of the study for futility.CONCLUSIONXenodiagnosis with larval I. scapularis ticks showed no evidence of B. burgdorferi in most patients after treatment, irrespective of symptoms. This may be due to absence of bacteria or to the low sensitivity of the technique in humans. This method is unlikely to detect persistent B. burgdorferi infection in humans and further research on the use of xenodiagnosis is unwarranted.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"275 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005239","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}
Samuel Starke,Keziah Thomas,Supriya Jasuja,Ronald Lubelchek
In a U.S. health department TB program serving primarily non-U.S.-born clients, 78% of those evaluated for latent TB infection initiated TB preventive therapy, with 71% completing treatment. Completion was lower among newly arrived migrants. A novel one-month isoniazid-rifapentine regimen (1HP) was well tolerated, with similar completion rates to conventional regimens.
{"title":"Short-Course Tuberculosis Preventive Therapy in a High Migration Setting: Early Experience With 1HP in Cook County, Illinois.","authors":"Samuel Starke,Keziah Thomas,Supriya Jasuja,Ronald Lubelchek","doi":"10.1093/cid/ciaf723","DOIUrl":"https://doi.org/10.1093/cid/ciaf723","url":null,"abstract":"In a U.S. health department TB program serving primarily non-U.S.-born clients, 78% of those evaluated for latent TB infection initiated TB preventive therapy, with 71% completing treatment. Completion was lower among newly arrived migrants. A novel one-month isoniazid-rifapentine regimen (1HP) was well tolerated, with similar completion rates to conventional regimens.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"36 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005022","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}
Chin Fen Neoh,Sharon C-A Chen,Arthur J Morris,Christopher H Heath,Shu Jin Tan,Rebekah Lane,Shio Yen Tio,Sze Yen Tay,Matthew B Roberts,Karina Kennedy,Sebastiaan J van Hal,Hugh C Murray,Robert Pickles,Natasha Marcella Vaselli,Abby Douglas,Karen Urbancic,Mahesh Menon,Adam Stewart,Julia C Howard,Caitlin Keighley,Spiros Miyakis,Rohan Beresford,Louise Cooley,Marjoree Sehu,Catriona L Halliday,Sarah Kidd,David C M Kong,Tim Spelman,Leon J Worth,Monica A Slavin,
BACKGROUNDUnderstanding the epidemiology of invasive non-Aspergillus mold infections is essential to inform effective therapy. Robust regional studies remain scarce. This study aimed to determine the epidemiology and infection characteristics of non-Aspergillus mold infections in Australasia.METHODSA 21-center, retrospective study of proven/probable non-Aspergillus mold infections from 2016 to 2023 was conducted in Australia and New Zealand. Data collected included demographic, clinical, microbiological, treatment and outcome information until 180 days of follow-up.RESULTSOf 421 cases, 346 (82.2%) were proven infections and 315 (74.8%) were localized. Lung (n=150/421, 35.6%) was the most common site of infection. Twenty cases (4.8%) were due to >1 non-Aspergillus mold pathogen, resulting in 443 isolates altogether. Dematiaceous molds, inclusive of Lomentospora prolificans (n=96, 21.7%), Scedosporium spp. (n=87, 19.6%) and other dematiaceous molds of various genera (n=48, 10.8%), were the most common (n=231, 52.1%), followed by Mucorales (n=141, 31.8%). Common underlying conditions were hematological malignancy (n=146/421, 34.7%) and diabetes mellitus (n=122/421, 29.0%) while 68 cases (16.2%) had no comorbidities. Lymphopenia was present in 46.6% (n=196/421). One-third (n=138/421, 32.8%) received antifungal prophylaxis 30 days before non-Aspergillus mold diagnosis and L. prolificans was the most common cause of breakthrough infections (p<0.001). All-cause 90-day mortality was 31.4% (n=132/421), with higher mortality observed in L. prolificans (n=51/89, 57.3%) and Mucorales (n=56/129, 43.4%) infections.CONCLUSIONSL. prolificans, Scedosporium spp. and Mucorales are the most frequent non-Aspergillus mold pathogens in Australasia, with other emerging species and mixed infections encountered. Mortality from L. prolificans and Mucorales infections remains high.
{"title":"Current Epidemiology and Infection Characteristics of Non-Aspergillus Mold Infections: A Multicenter Study in Australia and New Zealand.","authors":"Chin Fen Neoh,Sharon C-A Chen,Arthur J Morris,Christopher H Heath,Shu Jin Tan,Rebekah Lane,Shio Yen Tio,Sze Yen Tay,Matthew B Roberts,Karina Kennedy,Sebastiaan J van Hal,Hugh C Murray,Robert Pickles,Natasha Marcella Vaselli,Abby Douglas,Karen Urbancic,Mahesh Menon,Adam Stewart,Julia C Howard,Caitlin Keighley,Spiros Miyakis,Rohan Beresford,Louise Cooley,Marjoree Sehu,Catriona L Halliday,Sarah Kidd,David C M Kong,Tim Spelman,Leon J Worth,Monica A Slavin, ","doi":"10.1093/cid/ciag029","DOIUrl":"https://doi.org/10.1093/cid/ciag029","url":null,"abstract":"BACKGROUNDUnderstanding the epidemiology of invasive non-Aspergillus mold infections is essential to inform effective therapy. Robust regional studies remain scarce. This study aimed to determine the epidemiology and infection characteristics of non-Aspergillus mold infections in Australasia.METHODSA 21-center, retrospective study of proven/probable non-Aspergillus mold infections from 2016 to 2023 was conducted in Australia and New Zealand. Data collected included demographic, clinical, microbiological, treatment and outcome information until 180 days of follow-up.RESULTSOf 421 cases, 346 (82.2%) were proven infections and 315 (74.8%) were localized. Lung (n=150/421, 35.6%) was the most common site of infection. Twenty cases (4.8%) were due to >1 non-Aspergillus mold pathogen, resulting in 443 isolates altogether. Dematiaceous molds, inclusive of Lomentospora prolificans (n=96, 21.7%), Scedosporium spp. (n=87, 19.6%) and other dematiaceous molds of various genera (n=48, 10.8%), were the most common (n=231, 52.1%), followed by Mucorales (n=141, 31.8%). Common underlying conditions were hematological malignancy (n=146/421, 34.7%) and diabetes mellitus (n=122/421, 29.0%) while 68 cases (16.2%) had no comorbidities. Lymphopenia was present in 46.6% (n=196/421). One-third (n=138/421, 32.8%) received antifungal prophylaxis 30 days before non-Aspergillus mold diagnosis and L. prolificans was the most common cause of breakthrough infections (p<0.001). All-cause 90-day mortality was 31.4% (n=132/421), with higher mortality observed in L. prolificans (n=51/89, 57.3%) and Mucorales (n=56/129, 43.4%) infections.CONCLUSIONSL. prolificans, Scedosporium spp. and Mucorales are the most frequent non-Aspergillus mold pathogens in Australasia, with other emerging species and mixed infections encountered. Mortality from L. prolificans and Mucorales infections remains high.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"36 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005023","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}
{"title":"The clinical thermometer as the first home test for infectious disease.","authors":"Michele Augusto Riva","doi":"10.1093/cid/ciag030","DOIUrl":"https://doi.org/10.1093/cid/ciag030","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005026","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}
Emily A Rosen,Elizabeth M Krantz,Allison Thibodeau,Keara Kennedy,Leah H Yoke,Frank Tverdek,Zahra Kassamali Escobar,Jason P Cooper,Masumi Ueda Oshima,Paul Hendrie,Marco Mielcarek,Catherine Liu
BACKGROUNDThe optimal frequency of repeat blood cultures in persistent febrile neutropenia (FN) remains unknown. This study aims to identify opportunities for blood culture diagnostic stewardship in persistent FN.METHODSThis is a retrospective cohort study of patients with hematology/oncology diagnoses and an FN episode >3 days. Generalized estimating equation logistic regression models were used to evaluate risk factors for new bloodstream infection (BSI) after FN day 3.RESULTSAmong 620 patients, median FN duration was 5 days and median blood culture bottles collected per patient was 12. On FN day 1, 25% of patients had a positive blood culture; on FN days 2-9, <5% of patients per day had a new organism isolated. Among 31 new organisms isolated after FN day 3, 8 (26%) were contaminants. Of 503 patients with ≥1 blood culture collected after FN day 3, 19 (4%) had a new BSI after FN day 3. FN onset in the peri-hematopoietic cell transplant (HCT) period (day -7 to +30) was associated with lower odds of new BSI after FN day 3 (OR 0.18; 95%CI [0.04-0.71]; p=0.01).Thirty-six patients died within 30 days after FN day 3, including 4 with a new BSI after FN day 3; 1 death was attributable to BSI after FN day 3.CONCLUSIONSDetection of new BSI after FN day 3 was uncommon, demonstrating low diagnostic yield of repeat blood cultures after FN day 3. FN episodes in the peri-HCT period may be a potential focus for blood culture diagnostic stewardship initiatives.
{"title":"Diagnostic Yield of Repeat Blood Cultures and Risk Factors for Bloodstream Infection in Persistent Febrile Neutropenia.","authors":"Emily A Rosen,Elizabeth M Krantz,Allison Thibodeau,Keara Kennedy,Leah H Yoke,Frank Tverdek,Zahra Kassamali Escobar,Jason P Cooper,Masumi Ueda Oshima,Paul Hendrie,Marco Mielcarek,Catherine Liu","doi":"10.1093/cid/ciag014","DOIUrl":"https://doi.org/10.1093/cid/ciag014","url":null,"abstract":"BACKGROUNDThe optimal frequency of repeat blood cultures in persistent febrile neutropenia (FN) remains unknown. This study aims to identify opportunities for blood culture diagnostic stewardship in persistent FN.METHODSThis is a retrospective cohort study of patients with hematology/oncology diagnoses and an FN episode >3 days. Generalized estimating equation logistic regression models were used to evaluate risk factors for new bloodstream infection (BSI) after FN day 3.RESULTSAmong 620 patients, median FN duration was 5 days and median blood culture bottles collected per patient was 12. On FN day 1, 25% of patients had a positive blood culture; on FN days 2-9, <5% of patients per day had a new organism isolated. Among 31 new organisms isolated after FN day 3, 8 (26%) were contaminants. Of 503 patients with ≥1 blood culture collected after FN day 3, 19 (4%) had a new BSI after FN day 3. FN onset in the peri-hematopoietic cell transplant (HCT) period (day -7 to +30) was associated with lower odds of new BSI after FN day 3 (OR 0.18; 95%CI [0.04-0.71]; p=0.01).Thirty-six patients died within 30 days after FN day 3, including 4 with a new BSI after FN day 3; 1 death was attributable to BSI after FN day 3.CONCLUSIONSDetection of new BSI after FN day 3 was uncommon, demonstrating low diagnostic yield of repeat blood cultures after FN day 3. FN episodes in the peri-HCT period may be a potential focus for blood culture diagnostic stewardship initiatives.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005031","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}
Subcutaneous antibiotic administration is increasingly recognized as a valuable alternative to intravenous therapy in selected clinical contexts. It is particularly advantageous for patients with poor venous access, frail or cachectic individuals, and in outpatient or palliative care settings, when oral options are not feasible. Subcutaneous delivery of antibiotics with predominantly time-dependent activity, particularly β-lactams (eg ceftriaxone, ertapenem) and glycopeptides (teicoplanin), allows attainment of therapeutic pharmacokinetic/pharmacodynamic (PK/PD) targets comparable to intravenous administration, while maintaining stable concentrations and reducing catheter-related complications. By contrast, PK/PD benefits are limited for agents with more concentration-dependent activity, such as aminoglycosides and fluoroquinolones due to reduced peak levels and local toxicity, whereas daptomycin shows favorable exposure and target attainment with acceptable tolerability. Available evidence suggests good tolerability, although regulatory frameworks remain limited. This multidisciplinary review, authored by infectious disease specialists, clinical pharmacologists, and nurses, summarizes current clinical experience, PK/PD data, and technical aspects of subcutaneous infusion.
{"title":"When and How to Use Subcutaneous Antibiotics.","authors":"Stefano Di Bella,Nicholas Geremia,Federico Pea,Markus Zeitlinger,Gianfranco Sanson,Jacopo Monticelli,Felix Bergmann,Christian Motet,Christophe Lambotte-Buffet,Verena Zerbato,Milo Gatti","doi":"10.1093/cid/ciaf691","DOIUrl":"https://doi.org/10.1093/cid/ciaf691","url":null,"abstract":"Subcutaneous antibiotic administration is increasingly recognized as a valuable alternative to intravenous therapy in selected clinical contexts. It is particularly advantageous for patients with poor venous access, frail or cachectic individuals, and in outpatient or palliative care settings, when oral options are not feasible. Subcutaneous delivery of antibiotics with predominantly time-dependent activity, particularly β-lactams (eg ceftriaxone, ertapenem) and glycopeptides (teicoplanin), allows attainment of therapeutic pharmacokinetic/pharmacodynamic (PK/PD) targets comparable to intravenous administration, while maintaining stable concentrations and reducing catheter-related complications. By contrast, PK/PD benefits are limited for agents with more concentration-dependent activity, such as aminoglycosides and fluoroquinolones due to reduced peak levels and local toxicity, whereas daptomycin shows favorable exposure and target attainment with acceptable tolerability. Available evidence suggests good tolerability, although regulatory frameworks remain limited. This multidisciplinary review, authored by infectious disease specialists, clinical pharmacologists, and nurses, summarizes current clinical experience, PK/PD data, and technical aspects of subcutaneous infusion.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"88 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005242","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}
Michihiko Goto,Anindita Bandyopadhyay,Qianyi Shi,Yaohua Wang,Eli N Perencevich,David Hernandez,W Nick Street
BACKGROUNDConventional hospital antibiograms summarize aggregated resistance rates, limiting their utility for individualized antimicrobial selection. Existing statistical and machine learning models predict each phenotype separately, ignoring correlations among resistance profiles. We developed novel multi-task extreme gradient boosting (XGBoost) models utilizing structured data in electronic health records (EHRs) to predict resistance to eight antimicrobial classes simultaneously and evaluated their performance within the Veterans Health Administration (VHA).METHODSWe conducted a retrospective multicenter study of Escherichia coli and Klebsiella spp. isolates collected at 127 hospitals and >1,400 clinics from January 2017 to September 2024. Data from January 2017 to September 2023 were used for model development, while data from October 2023 to September 2024 were used for simulated prospective testing. Model performances were compared to hospital antibiograms and single-target XGBoost models.RESULTSThe training cohort included 536,252 E. coli and 246,898 Klebsiella spp. isolates; the test cohort included 75,138 and 38,015 isolates, respectively. On the test data, the multi-task model achieved overall areas under the receiver operating characteristic curve (AUROCs) of 0.779 (E. coli) and 0.810 (Klebsiella spp.), with good to excellent per-class performance (AUROCs range: 0.743-0.847). A multi-task approach improved calibration and decreased false negative rates for carbapenem resistance, while predicting individualized resistance probabilities for all target antimicrobials simultaneously ("personalized antibiograms").CONCLUSIONSA multi-task XGBoost framework can accurately predict individualized resistance profiles for common Gram-negative pathogens, outperforming conventional antibiograms and single-target models. Personalized antibiograms may enhance the selection of empiric therapy, including the detection of carbapenem resistance in low-endemicity settings.
{"title":"Personalized Antibiogram: A Novel Multi-Task Machine Learning Framework for Simultaneous Prediction of Antimicrobial Resistance Profile with Enhanced Detection of Carbapenem Resistance in Enterobacteriaceae.","authors":"Michihiko Goto,Anindita Bandyopadhyay,Qianyi Shi,Yaohua Wang,Eli N Perencevich,David Hernandez,W Nick Street","doi":"10.1093/cid/ciag027","DOIUrl":"https://doi.org/10.1093/cid/ciag027","url":null,"abstract":"BACKGROUNDConventional hospital antibiograms summarize aggregated resistance rates, limiting their utility for individualized antimicrobial selection. Existing statistical and machine learning models predict each phenotype separately, ignoring correlations among resistance profiles. We developed novel multi-task extreme gradient boosting (XGBoost) models utilizing structured data in electronic health records (EHRs) to predict resistance to eight antimicrobial classes simultaneously and evaluated their performance within the Veterans Health Administration (VHA).METHODSWe conducted a retrospective multicenter study of Escherichia coli and Klebsiella spp. isolates collected at 127 hospitals and >1,400 clinics from January 2017 to September 2024. Data from January 2017 to September 2023 were used for model development, while data from October 2023 to September 2024 were used for simulated prospective testing. Model performances were compared to hospital antibiograms and single-target XGBoost models.RESULTSThe training cohort included 536,252 E. coli and 246,898 Klebsiella spp. isolates; the test cohort included 75,138 and 38,015 isolates, respectively. On the test data, the multi-task model achieved overall areas under the receiver operating characteristic curve (AUROCs) of 0.779 (E. coli) and 0.810 (Klebsiella spp.), with good to excellent per-class performance (AUROCs range: 0.743-0.847). A multi-task approach improved calibration and decreased false negative rates for carbapenem resistance, while predicting individualized resistance probabilities for all target antimicrobials simultaneously (\"personalized antibiograms\").CONCLUSIONSA multi-task XGBoost framework can accurately predict individualized resistance profiles for common Gram-negative pathogens, outperforming conventional antibiograms and single-target models. Personalized antibiograms may enhance the selection of empiric therapy, including the detection of carbapenem resistance in low-endemicity settings.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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