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Dynamic characteristics of high-risk HPV infection in women with low-grade cervical intraepithelial neoplasia, based on a community longitudinal study. 基于社区纵向研究的低级别宫颈上皮内瘤变妇女中高危 HPV 感染的动态特征。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-04 DOI: 10.1007/s10096-024-05036-x
Kailu Zhao, Huimin Li, Meng Cui, Li Song, Yuanjing Lyu, Ling Ding, Jintao Wang

Background: High-risk human papillomavirus (HR-HPV) infection is the primary cause of cervical cancer and precancerous lesions. Approximately 35% of women with low-grade cervical intraepithelial neoplasia (CIN1) may experience persistence or progression to high-grade lesions. Yet, the dynamic characteristics of HR-HPV infection in women with CIN1 remain unclear.

Methods: A total of 564 women diagnosed with CIN1, recruited from a community-based cohort, underwent a 24-month follow-up at 6th, 12th, and 24th month intervals. Hazard ratios (HRs) with 95% confidence interval (CI) were calculated to evaluate the risk of HR-HPV infection prognosis and their associated factors. Kaplan-Meier survival curves illustrated the dynamic changes of HR-HPV infection and association between HR-HPV infection prognosis and various influencing factors.

Results: HPV16 was the predominant carcinogenic genotype, followed by HPV58 and HPV52. Over the 24-month follow-up, persistent HPV16 infection occurred in 10.6% of women, with 14.4% converting from positive to negative and 4% developing HPV16 positivity from baseline HR-HPV negativity. Rates of persistent infection for HPV58, 52, 18, and 56 decreased over time, with HPV58, 52, and 31 infections more likely to turn HR-HPV negative. Additionally, rates of positive conversion from negative for HPV58, 56, 33, and 66 increased with extended follow-up time. Variables associated with dynamic characteristics of HR-HPV infection prognosis included personal hygiene, age of first menarche, age at first sexual intercourse, educational level, age, and menopausal status (all P < 0.05).

Conclusions: These findings contribute to understanding the dynamic characteristics of HR-HPV infection prognosis in women with CIN1 and its association with non-viral factors.

背景:高危人乳头瘤病毒(HR-HPV)感染是宫颈癌和癌前病变的主要原因。大约35%患有低级别宫颈上皮内瘤变(CIN1)的女性可能持续存在或进展为高级别病变。然而,CIN1女性HR-HPV感染的动态特征仍不清楚。方法:从社区队列中招募了564名诊断为CIN1的女性,分别在第6、12和24个月的间隔进行了24个月的随访。计算95%可信区间(CI)的风险比(hr),评估HR-HPV感染的预后风险及其相关因素。Kaplan-Meier生存曲线显示了HR-HPV感染的动态变化,以及HR-HPV感染预后与各种影响因素的关系。结果:HPV16为主要致癌基因型,其次为HPV58和HPV52。在24个月的随访中,10.6%的女性发生了持续的HPV16感染,其中14.4%从阳性转化为阴性,4%从基线HR-HPV阴性发展为HPV16阳性。HPV58、52、18和56的持续感染率随着时间的推移而下降,HPV58、52和31的感染更有可能变为HR-HPV阴性。此外,HPV58、56、33和66的阴性转化率随着随访时间的延长而增加。与HR-HPV感染预后动态特征相关的变量包括个人卫生、初潮年龄、初次性交年龄、受教育程度、年龄和绝经状态(均为P)。结论:这些发现有助于了解CIN1女性HR-HPV感染预后的动态特征及其与非病毒因素的关系。
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引用次数: 0
Diagnostic accuracy of Xpert MTB/RIF Ultra for detecting pulmonary tuberculosis and rifampicin resistance: a systematic review and meta-analysis. Xpert MTB/RIF Ultra 检测肺结核和利福平耐药性的诊断准确性:系统综述和荟萃分析。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-04 DOI: 10.1007/s10096-024-05032-1
Man-Qing Wang, Ya-Fang Zheng, Yu-Qi Hu, Jin-Xia Huang, Zi-Xin Yuan, Zu-Yan Wu, Lu-Fang Huang, Chu-Ting Tang, Feng-Yi Zhang, Yan Chen, Jin-Ke He, Xu-Guang Guo, Bao-Mei Yan

Background: Public health issues related to tuberculosis still exist. Because Xpert MTB/RIF Ultra is more effective than conventional TB diagnostic techniques are, it is now regarded as an emerging technology. The diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculosis was assessed in this systematic study.

Methods: We searched the PubMed, Cochrane, EMBASE, and Web of Science databases for pertinent literature published before January 18, 2024. The quality of the collected literature was assessed via Review Manager 5.3 software, which applies the quality assessment of diagnostic accuracy studies criteria. Using Metadisc 1.40 software, the sensitivity, specificity, and summary receiver operating characteristic curves were plotted and examined. Stata 12.0 was the program we utilized to assess publication bias in this investigation. The Prospero prospective register of systematic reviews included this study (reference number CRD42024569674).

Results: Analysis of 187 fourfold tables from 72 studies revealed that Xpert MTB/RIF Ultra demonstrated an overall pooled sensitivity of 76% and specificity of 95% for detecting pulmonary tuberculosis. The positive likelihood ratio (PLR) was 14.91, and the negative likelihood ratio (NLR) was 0.23, with an area under the curve (AUC) of 0.9351 and a diagnostic odds ratio (DOR) of 73.39. For detecting rifampin resistance, the combined sensitivity and specificity were 94% and 97%, respectively. The pooled PLR was 24.94, the NLR was 0.07, and the DOR was 429.05. The area under the summary receiver operating characteristic (SROC) curve was 0.9868.

Conclusion: In conclusion, developing effective laboratory diagnostic tools for identifying Mycobacterium tuberculosis is essential for epidemiological research. This study demonstrated that Xpert MTB/RIF Ultra effectively diagnosed Mycobacterium tuberculosis infection, including pulmonary tuberculosis, as well as rifampin resistance, highlighting its potential as a valuable tool for both diagnosis and resistance detection.

背景:与结核病有关的公共卫生问题仍然存在。由于专家MTB/RIF Ultra比传统的结核病诊断技术更有效,它现在被视为一种新兴技术。本系统研究评估了Xpert MTB/RIF Ultra对结核病的诊断准确性。方法:检索PubMed、Cochrane、EMBASE和Web of Science数据库,检索2024年1月18日前发表的相关文献。收集文献的质量通过Review Manager 5.3软件进行评估,该软件应用诊断准确性研究标准的质量评估。使用Metadisc 1.40软件,绘制并检查敏感性、特异性和总体受试者工作特征曲线。Stata 12.0是我们在本研究中用于评估发表偏倚的程序。普洛斯彼罗前瞻性系统评价登记纳入了本研究(参考号CRD42024569674)。结果:对72项研究的187个四重表的分析显示,Xpert MTB/RIF Ultra检测肺结核的总总敏感性为76%,特异性为95%。阳性似然比(PLR)为14.91,阴性似然比(NLR)为0.23,曲线下面积为0.9351,诊断优势比(DOR)为73.39。检测利福平耐药的敏感性和特异性分别为94%和97%。合并PLR为24.94,NLR为0.07,DOR为429.05。受试者工作特征(SROC)曲线下面积为0.9868。结论:开发有效的实验室诊断工具对流行病学研究具有重要意义。这项研究表明,Xpert MTB/RIF Ultra有效地诊断了结核分枝杆菌感染,包括肺结核,以及利福平耐药性,突出了其作为诊断和耐药性检测的有价值工具的潜力。
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引用次数: 0
In vitro activity of cefepime-tazobactam against oxyimino cephalosporin-resistant clinical isolates of E. coli: exploring a potential carbapenem-sparing strategy. 头孢吡肟-他唑巴坦对耐氧亚胺类头孢菌素临床分离株的体外活性:探索潜在的碳青霉烯节约策略。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-03 DOI: 10.1007/s10096-024-05033-0
Rimjhim Kanaujia, Satinder Kaur, Manisha Biswal, Pallab Ray, Navneet Sharma, Archana Angrup

Cefepime-tazobactam (FEP-TAZ) consists of cefepime combined with tazobactam, a penicillanic acid-sulfone recognized as an established beta-lactamase inhibitor. This study aims to investigate the in-vitro effectiveness of FEP-TAZ against cefepime-resistant clinical isolates of Escherichia coli (E. coli). A total of 105 E. coli clinical isolates characterized by cefepime-resistant/susceptible dose-dependent and carbapenem-sensitive profiles were tested for susceptibility by broth microdilution (BMD) method against cefepime and FEP-TAZ (tazobactam at a fixed concentration of 4 mg/L). Minimum inhibitory concentration (MIC) values for cefepime were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (M100-2022). Simultaneously, we also performed Disk-diffusion (DD) to observe the concordance between BMD and DD. FEP-TAZ exhibited inhibitory efficacy against 83.8% of E. coli isolates, markedly reducing the geometric mean from 20.4 to 1.9. Comparative analysis with DD revealed concordance with MIC for all isolates except four isolates. FEP-TAZ demonstrated potent activity against E.coli. This may be used as a carbapenem-sparing agent for the treatment of serious infections caused by cefepime-resistant Gram-negative bacilli. Furthermore, in settings where BMD implementation poses challenges, the pragmatic application of DD proves to be a viable alternative.

头孢吡肟-他唑巴坦(FEP-TAZ)由头孢吡肟和他唑巴坦组成,他唑巴坦是一种青霉素砜,是公认的β-内酰胺酶抑制剂。本研究旨在探讨 FEP-TAZ 对头孢吡肟耐药临床大肠埃希菌(大肠杆菌)分离株的体外疗效。研究人员采用肉汤微量稀释法(BMD),对头孢吡肟和 FEP-TAZ(他唑巴坦,固定浓度为 4 毫克/升)进行了药敏试验。头孢吡肟的最低抑菌浓度(MIC)值采用临床和实验室标准协会(CLSI)肉汤微稀释法(M100-2022)测定。同时,我们还进行了盘扩散(DD),以观察 BMD 和 DD 之间的一致性。FEP-TAZ 对 83.8% 的大肠杆菌分离物具有抑制效果,几何平均数从 20.4 显著降至 1.9。与 DD 的比较分析表明,除 4 个分离物外,对所有分离物的 MIC 均一致。FEP-TAZ 对大肠杆菌具有很强的活性。该药物可作为碳青霉烯类药物,用于治疗耐头孢吡肟革兰氏阴性杆菌引起的严重感染。此外,在实施 BMD 存在挑战的情况下,DD 的实际应用证明是一种可行的替代方法。
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引用次数: 0
Evaluation of metagenomic next-generation sequencing (mNGS) combined with quantitative PCR: cutting-edge methods for rapid diagnosis of non-invasive fungal rhinosinusitis. 元基因组新一代测序(mNGS)结合定量 PCR 的评估:快速诊断非侵袭性真菌性鼻炎的前沿方法。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-10-23 DOI: 10.1007/s10096-024-04962-0
Xiao Liu, Shaoqin Zhou, Rong Yan, Caifeng Xia, Ruoning Xue, Zhe Wan, Ruoyu Li, Sybren de Hoog, Sarah A Ahmed, Quangui Wang, Yinggai Song

Purpose: Fungal rhinosinusitis is a significant and growing health concern in arid regions, with an increasing incidence over recent decades. Without timely and appropriate management, it can lead to severe complications, including potential intracranial spread. This study aims to establish efficient and rapid diagnostics for non-invasive fungal rhinosinusitis (FRS), addressing the challenge of its difficult-to-culture diagnosis.

Methods: Twenty-eight patients suspected of FRS were studied using endoscopic sinus surgery to obtain tissue samples for histopathology, direct microscopy, fungal culture, quantitative PCR (qPCR) and metagenomic next-generation sequencing (mNGS) detection. A patented qPCR targeting prevalent Aspergillus species was evaluated.

Results: The patient cohort had a male-to-female ratio of 9:14, with disease duration up to 50 years. Histopathologically, 23 out of 28 cases were positive. Fungal culture exhibited a sensitivity of 21.74%, with one false positive. qPCR and mNGS showed 100% sensitivity and specificity, with a 100% consistency rate for identification at the species level (23/23), and potential detection of cases with co-infections. The most common pathogen was A. flavus, followed by A. fumigatus and A. niger. Two cases involved mixed infections of A. fumigatus and A. flavus.

Conclusion: qPCR and mNGS proved effective in rapidly identifying fungi from fresh sinus tissue that are challenging to culture, surpassing conventional methods. However, further evaluation and optimization with a larger cohort of patients are necessary. Histopathology is still recommended to confirm the clinical significance of the detected fungal species.

目的:真菌性鼻炎是干旱地区日益严重的健康问题,近几十年来发病率不断上升。如果不及时采取适当的治疗措施,可能会导致严重的并发症,包括潜在的颅内扩散。本研究旨在为非侵入性真菌性鼻炎(FRS)建立高效、快速的诊断方法,解决其难以培养诊断的难题:方法:研究人员对 28 名疑似鼻窦炎患者进行了鼻窦内窥镜手术,获取组织样本进行组织病理学、直接显微镜检查、真菌培养、定量 PCR (qPCR) 和元基因组新一代测序 (mNGS) 检测。对一种针对流行曲霉菌种的专利 qPCR 进行了评估:患者男女比例为 9:14,病程长达 50 年。从组织病理学角度来看,28 个病例中有 23 个呈阳性。qPCR 和 mNGS 的灵敏度和特异性均为 100%,物种鉴定的一致性为 100%(23/23),并可发现合并感染的病例。最常见的病原体是黄曲霉,其次是烟曲霉和黑曲霉。结论:事实证明,qPCR 和 mNGS 能有效地从新鲜鼻窦组织中快速鉴定出难以培养的真菌,超过了传统方法。然而,有必要对更多患者进行进一步评估和优化。仍建议采用组织病理学方法确认检测到的真菌种类的临床意义。
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引用次数: 0
A prospective analysis of clinical and parasitological outcomes after treatment or a wait-and-see approach of Dientamoeba fragilis infection in an adult general practice population. 前瞻性分析成人全科医生对脆弱片阿米巴感染采取治疗或观望态度后的临床和寄生虫学结果。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI: 10.1007/s10096-024-04989-3
Hanna M J L Hazenberg, Theo G Mank, Caterina Band, Sjoerd M Euser, Ellert J van Soest

Purpose: Dientamoeba fragilis is a protozoan frequently encountered in stool samples globally. It is debated whether Dientamoeba fragilis carries pathogenic capacities. This study prospectively analyses clinical and parasitological outcomes after treatment or a wait-and-see approach of Dientamoeba fragilis infection in a general practice adult population.

Methods: In this prospective observational cohort study 113 adult patients with a positive Polymerase Chain Reaction (PCR) test result for D. fragilis (T0) in a primary care setting, were followed-up longitudinally with a control PCR-test and microscopic stool examination at 30 days (T1) and 90 days (T2) after inclusion. Standardized patient-reported questionnaires including treatment details and the adjusted Irritable Bowel Syndrome-Severity Score (IBS-SS) were retrieved at T0, T1 and T2.

Results: Parasitology and questionnaires were retrieved from 87 participants at T0 and T1, and 74 at T2. Treated patients(n = 64) more often tested PCR negative at T1 (64.1% vs. 16.4%, p < 0.001) and T2 (67.3% vs. 5.3%, p < 0.001) compared to untreated patients. No difference in decline in IBS-SS was seen comparing the treatment and non-treatment groups at T1 (p = 0.403) or T2 (p = 1.00).

Conclusion: A short and long term increased parasitological clearance is shown with treatment of clioquinol or metronidazole compared with no treatment. A clear and significant correlation between parasitological cure and decline of clinical complaints as reported by the participants could not be established.

目的:脆弱片阿米巴是全球粪便样本中经常出现的一种原生动物。脆弱片阿米巴是否具有致病能力尚存争议。本研究前瞻性地分析了普通成人群体中脆弱片阿米巴感染后的临床和寄生虫学结果:在这项前瞻性观察性队列研究中,对初级医疗机构中113名PCR检测结果呈阳性(T0)的成人患者进行了纵向随访,并在入院后30天(T1)和90天(T2)进行了对照PCR检测和粪便镜检。在 T0、T1 和 T2 期 间回收了标准化的患者报告问卷,其中包括治疗细节和调整后的肠易激综合征严重程度评分(IBS-SS):在 T0 和 T1 对 87 名参与者进行了寄生虫检查和问卷调查,在 T2 对 74 名参与者进行了寄生虫检查和问卷调查。接受治疗的患者(64 人)在 T1 阶段的 PCR 检测结果多为阴性(64.1% 对 16.4%,P 结论:短期和长期的寄生虫感染率会增加:与不治疗相比,使用氯喹酚或甲硝唑治疗后,短期和长期的寄生虫清除率均有所提高。寄生虫学治愈与参与者报告的临床症状减轻之间没有明显的相关性。
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引用次数: 0
Incidence of colistin heteroresistance among carbapenem-resistant Acinetobacter baumannii clinical isolates in a tertiary care hospital in Pakistan. 巴基斯坦一家三级医院中耐碳青霉烯类鲍曼不动杆菌临床分离株的可乐定异抗性发生率。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-11-15 DOI: 10.1007/s10096-024-04988-4
Azka Zulfiqar, Faisal Hanif, Rafia Irfan, Amber Qasim, Javaid Usman

Purpose: The emergence of colistin-resistant and heteroresistant strains of carbapenem-resistant Acinetobacter baumannii (CRAB) complicates treatment and exacerbates the global health crisis of drug-resistant bacteria. This study aims to investigate the incidence and clinical implications of colistin heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates from a tertiary hospital in Pakistan.

Materials and methods: A total of 130 CRAB isolates were collected from December 2022 to December 2023. Colistin susceptibility was assessed using broth microdilution, and heteroresistance was detected through population analysis profiling.

Results: Heteroresistance (HR) was identified in 31.5% (41/130) of the isolates, while 7.7% were colistin-resistant, despite initial susceptibility indicated by broth microdilution. Clinical data revealed that HR was associated with significant 14-day clinical failure but not with 30-day all-cause mortality. Heteroresistant strains showed extensive multidrug resistance, posing a serious threat to effective treatment.

Conclusions: The study highlights the critical need for accurate detection of colistin HR to prevent treatment failure and improve patient outcomes. The prevalence of colistin HR underscores the necessity for revised diagnostic and treatment strategies in Pakistan, emphasizing the importance of recognizing and addressing this emerging threat in healthcare settings.

目的:耐碳青霉烯类鲍曼不动杆菌(CRAB)中出现的耐可乐定和杂合耐药菌株使治疗复杂化,并加剧了耐药细菌的全球健康危机。本研究旨在调查巴基斯坦一家三级医院分离的耐碳青霉烯类鲍曼不动杆菌中可乐定异耐药性的发生率和临床影响:从2022年12月至2023年12月,共收集了130株CRAB分离株。使用肉汤微量稀释法评估了对秋水仙素的敏感性,并通过群体分析图谱检测了异抗性:结果:31.5%(41/130)的分离菌株中发现了异抗性(HR),7.7%的分离菌株对秋水仙素耐药,尽管肉汤微量稀释法显示了最初的药敏性。临床数据显示,HR 与 14 天的严重临床失败有关,但与 30 天的全因死亡率无关。异耐药菌株表现出广泛的多药耐药性,对有效治疗构成严重威胁:本研究强调了准确检测秋水仙素耐药菌株以防止治疗失败并改善患者预后的迫切需要。耐秋水仙素菌株的流行凸显了在巴基斯坦修订诊断和治疗策略的必要性,强调了在医疗保健环境中认识和应对这一新兴威胁的重要性。
{"title":"Incidence of colistin heteroresistance among carbapenem-resistant Acinetobacter baumannii clinical isolates in a tertiary care hospital in Pakistan.","authors":"Azka Zulfiqar, Faisal Hanif, Rafia Irfan, Amber Qasim, Javaid Usman","doi":"10.1007/s10096-024-04988-4","DOIUrl":"10.1007/s10096-024-04988-4","url":null,"abstract":"<p><strong>Purpose: </strong>The emergence of colistin-resistant and heteroresistant strains of carbapenem-resistant Acinetobacter baumannii (CRAB) complicates treatment and exacerbates the global health crisis of drug-resistant bacteria. This study aims to investigate the incidence and clinical implications of colistin heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates from a tertiary hospital in Pakistan.</p><p><strong>Materials and methods: </strong>A total of 130 CRAB isolates were collected from December 2022 to December 2023. Colistin susceptibility was assessed using broth microdilution, and heteroresistance was detected through population analysis profiling.</p><p><strong>Results: </strong>Heteroresistance (HR) was identified in 31.5% (41/130) of the isolates, while 7.7% were colistin-resistant, despite initial susceptibility indicated by broth microdilution. Clinical data revealed that HR was associated with significant 14-day clinical failure but not with 30-day all-cause mortality. Heteroresistant strains showed extensive multidrug resistance, posing a serious threat to effective treatment.</p><p><strong>Conclusions: </strong>The study highlights the critical need for accurate detection of colistin HR to prevent treatment failure and improve patient outcomes. The prevalence of colistin HR underscores the necessity for revised diagnostic and treatment strategies in Pakistan, emphasizing the importance of recognizing and addressing this emerging threat in healthcare settings.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"151-158"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Group A Streptococcus vulvovaginitis in Spain, 2011-2023: antibiotic resistance and emm-type distribution. 2011-2023 年西班牙 A 群链球菌外阴阴道炎:抗生素耐药性和 emm 型分布。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.1007/s10096-024-04971-z
Elena Sánchez-Báscones, Alba Bellés-Bellés, Pilar Villalón Panzano, Noelia Garrido Castrillo, Andrea Castellano Verdasco, Albert Bernet Sánchez, Saray Mormeneo Bayo, Eric López González, Iván Prats Sánchez, Mercè García-González

An increase in Group A Streptococcus vulvovaginitis was detected in 2023: The average number of cases per year was 13 during 2011-2017. Twenty-five and 27 cases were reported in 2018 and 2019 followed by a decline coinciding with the COVID-19 pandemic. The 2023 increase surpassed previous data. The most frequent resistances were to erythromycin (11.3%;) and tetracycline (8.8%). Eleven different emm-types were detected among 30 GAS isolated in 2023: emm 1 was predominant (36.7%) followed by emm 89 (20%), emm 87 (10%) and emm 28 (6.7%). GAS should be increasingly considered in women with vulvovaginitis.

2023 年发现 A 群链球菌外阴阴道炎病例有所增加:2011-2017年期间,每年平均病例数为13例。2018年和2019年分别报告了25例和27例病例,随后随着COVID-19大流行而下降。2023 年的增长超过了之前的数据。最常见的耐药性是红霉素(11.3%;)和四环素(8.8%)。在 2023 年分离出的 30 例 GAS 中,检测到 11 种不同的 emm 类型:emm 1 型占主导地位(36.7%),其次是 emm 89 型(20%)、emm 87 型(10%)和 emm 28 型(6.7%)。患有外阴阴道炎的妇女应越来越多地考虑 GAS。
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引用次数: 0
Role of letermovir therapeutic drug monitoring for cytomegalovirus prophylaxis in allogeneic hematopoietic stem cell transplantation recipients: a prospective study. 同种异体造血干细胞移植受者预防巨细胞病毒的利特莫韦治疗药物监测作用:一项前瞻性研究。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-11-09 DOI: 10.1007/s10096-024-04977-7
Yulan Qiu, Xiaoning Wang, Juan Ren, Yijing Zhang, Chuqi Bai, Sasa Hu, Taotao Wang, Jiaojiao Chen, Chuhui Wang, Pengcheng He, Yalin Dong

Purpose: The role of therapeutic drug monitoring (TDM) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receiving letermovir has not yet been clarified. This study is to explore letermovir trough concentration (Cmin) correlation with its clinical efficacy and adverse events, and factors affecting its plasma concentrations.

Methods: A prospective, non-interventional study was performed in allo-HSCT recipients receiving letermovir prophylaxis. Plasma concentrations were determined using high-performance liquid chromatography-tandem mass spectrometry. Data analysis was performed using logistic regression, linear regression, and classification and regression tree (CART) models.

Results: 701 trough concentrations from 71 recipients were included, uncovering pronounced intra- and inter-individual variability in letermovir Cmin. During 24-week follow-up, CMV infection incidence was 16.4%. A significant correlation was identified between letermovir Cmin and its clinical efficacy, and the CART model showed an increased risk of CMV infection when Cmin ≤ 2731 ng/mL. However, no clear correlation was found between Cmin and adverse events. Gastrointestinal graft-versus-host disease, cyclosporine Cmin, gender, and concomitant medications, including mycophenolate mofetil, ondansetron, caspofungin, and methylprednisolone, may impact letermovir Cmin. Additionally, coadministration with cyclosporine injection significantly decreased median letermovir Cmin compared with cyclosporine capsules (2311 vs. 3386 ng/mL). Moreover, with the extension of time post-transplant, trough concentrations of both cyclosporine and letermovir significantly decreased.

Conclusion: TDM for letermovir may be beneficial in allo-HSCT recipients considering the variability in letermovir Cmin and its correlation with clinical efficacy. Moreover, drug interactions and the effects of changes in cyclosporine dosage forms or concentrations require careful monitoring for their effect on letermovir Cmin.

目的:治疗药物监测(TDM)在接受来特莫韦治疗的异基因造血干细胞移植(allo-HSCT)受者中的作用尚未明确。本研究旨在探讨来曲莫韦谷浓度(Cmin)与其临床疗效和不良反应的相关性,以及影响其血浆浓度的因素:这项前瞻性、非干预性研究针对接受来特莫韦预防治疗的allo-HSCT受者。采用高效液相色谱-串联质谱法测定血浆浓度。数据分析采用逻辑回归、线性回归和分类回归树(CART)模型:结果:共纳入了 71 名受试者的 701 个谷浓度,发现了来特莫韦 Cmin 在个体内和个体间的明显差异。随访 24 周期间,CMV 感染率为 16.4%。来特莫韦 Cmin 与临床疗效之间存在明显的相关性,CART 模型显示,当 Cmin ≤ 2731 纳克/毫升时,CMV 感染风险增加。然而,在 Cmin 与不良事件之间没有发现明确的相关性。胃肠道移植物抗宿主疾病、环孢素 Cmin、性别以及同时服用的药物(包括霉酚酸酯、昂丹司琼、卡泊芬净和甲基强的松龙)可能会影响利特莫韦 Cmin。此外,与环孢素胶囊相比,与环孢素注射液联合用药可显著降低来曲米韦 Cmin 中位数(2311 对 3386 纳克/毫升)。此外,随着移植后时间的延长,环孢素和来特莫韦的谷浓度均显著下降:结论:考虑到来特莫韦 Cmin 的变化及其与临床疗效的相关性,来特莫韦的 TDM 可能对异体 HSCT 受者有益。此外,药物相互作用以及环孢素剂型或浓度变化的影响也需要仔细监测,以了解其对来特莫韦 Cmin 的影响。
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引用次数: 0
PhenoMATRIX™ for the screening of Group B Streptococcus (GBS) carriage in pregnant women: ready to get rid of the LIM broth? 用于筛查孕妇乙型链球菌(GBS)携带情况的 PhenoMATRIX™:准备好摆脱 LIM 肉汤的束缚了吗?
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-11-09 DOI: 10.1007/s10096-024-04985-7
Abdessalam Cherkaoui, Gesuele Renzi, Jacques Schrenzel

There is a constant need to reduce turn-around times and keep costs as low as possible for the carriage screening of GBS in pregnant patients. Laboratory automation might provide an edge in this field. The objectives of the present study were: i) to compare the performance of the direct chromID™ Strepto B agar (CA) plating against LIM-broth enriched plating on CA for the detection of GBS from vagino-rectal screening-swabs; and ii) to assess the usage of PhenoMATRIX™ for the automated screening of GBS. Between January 2021 and December 2023, 9'107 vagino-rectal specimens were collected from pregnant women at Geneva University Hospitals and were used to address the first objective. There was a small difference in the GBS detection rates between direct CA plating (13.2%; 1'202/9'107) and LIM-broth enriched plating on CA (13.2%; 1'198/9'107). Based on the LIM-broth enrichment results, the sensitivity and specificity of the direct CA plating were 98.3% (95% CI, 97.3%-98.9%) and 99.7% (95% CI, 99.5%-99.8%), respectively. Importantly, for 25 specimens, GBS growth was only detected by direct CA plating. We used a random set of 8'768 CA plate pictures for the machine learning of PhenoMATRIX™. The validation was carried out on an additional set of 830 CA plate pictures. The sensitivity and specificity of PhenoMATRIX™ were 100% (95% CI, 96.6%-100.0%) and 90.2% (95% CI, 87.8%-92.1%), respectively. We established that for GBS screening, the performance of direct CA plating is not inferior to the LIM-broth enriched approach. By relying on PhenoMATRIX™, the negative predictive value for GBS screening reaches 100% (95% CI, 99.4%-100.0%), enabling the automatic release of GBS-negative cases within 24 h.

在对孕妇进行肠道病毒携带筛查时,需要不断缩短周转时间并尽可能降低成本。实验室自动化可为这一领域提供优势。本研究的目的是:i) 比较直接 chromID™ Strepto B 琼脂 (CA) 镀膜与 LIM-broth 富集镀膜在从阴道直肠筛查拭子中检测 GBS 方面的性能;ii) 评估 PhenoMATRIX™ 在自动筛查 GBS 方面的应用。2021 年 1 月至 2023 年 12 月期间,日内瓦大学医院从孕妇处采集了 9 107 份阴道直肠标本,用于实现第一个目标。CA直接镀膜(13.2%;1'202/9'107)和CA上的LIM-broth富集镀膜(13.2%;1'198/9'107)的GBS检出率差异很小。根据 LIM-菌落富集结果,CA 直接镀膜的敏感性和特异性分别为 98.3% (95% CI, 97.3%-98.9%) 和 99.7% (95% CI, 99.5%-99.8%) 。重要的是,有 25 份标本只能通过直接 CA 镀层检测到 GBS 生长。我们使用一组随机的 8 768 张 CA 平板图片对 PhenoMATRIX™ 进行机器学习。在另外一组 830 张 CA 平板图片上进行了验证。PhenoMATRIX™ 的灵敏度和特异度分别为 100%(95% CI,96.6%-100.0%)和 90.2%(95% CI,87.8%-92.1%)。我们证实,在 GBS 筛查中,直接 CA 镀膜法的效果并不亚于 LIM 盆富集法。依靠 PhenoMATRIX™,GBS 筛查的阴性预测值达到 100%(95% CI,99.4%-100.0%),可在 24 小时内自动发布 GBS 阴性病例。
{"title":"PhenoMATRIX™ for the screening of Group B Streptococcus (GBS) carriage in pregnant women: ready to get rid of the LIM broth?","authors":"Abdessalam Cherkaoui, Gesuele Renzi, Jacques Schrenzel","doi":"10.1007/s10096-024-04985-7","DOIUrl":"10.1007/s10096-024-04985-7","url":null,"abstract":"<p><p>There is a constant need to reduce turn-around times and keep costs as low as possible for the carriage screening of GBS in pregnant patients. Laboratory automation might provide an edge in this field. The objectives of the present study were: i) to compare the performance of the direct chromID™ Strepto B agar (CA) plating against LIM-broth enriched plating on CA for the detection of GBS from vagino-rectal screening-swabs; and ii) to assess the usage of PhenoMATRIX™ for the automated screening of GBS. Between January 2021 and December 2023, 9'107 vagino-rectal specimens were collected from pregnant women at Geneva University Hospitals and were used to address the first objective. There was a small difference in the GBS detection rates between direct CA plating (13.2%; 1'202/9'107) and LIM-broth enriched plating on CA (13.2%; 1'198/9'107). Based on the LIM-broth enrichment results, the sensitivity and specificity of the direct CA plating were 98.3% (95% CI, 97.3%-98.9%) and 99.7% (95% CI, 99.5%-99.8%), respectively. Importantly, for 25 specimens, GBS growth was only detected by direct CA plating. We used a random set of 8'768 CA plate pictures for the machine learning of PhenoMATRIX™. The validation was carried out on an additional set of 830 CA plate pictures. The sensitivity and specificity of PhenoMATRIX™ were 100% (95% CI, 96.6%-100.0%) and 90.2% (95% CI, 87.8%-92.1%), respectively. We established that for GBS screening, the performance of direct CA plating is not inferior to the LIM-broth enriched approach. By relying on PhenoMATRIX™, the negative predictive value for GBS screening reaches 100% (95% CI, 99.4%-100.0%), enabling the automatic release of GBS-negative cases within 24 h.</p>","PeriodicalId":11782,"journal":{"name":"European Journal of Clinical Microbiology & Infectious Diseases","volume":" ","pages":"63-69"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular detection of Staphylococcus aureus in urine in patients with S. aureus bacteremia: an exploratory study. 金黄色葡萄球菌菌血症患者尿液中金黄色葡萄球菌的分子检测:一项探索性研究。
IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.1007/s10096-024-04969-7
Franziska Schuler, Achim J Kaasch, Frieder Schaumburg

Purpose: Staphylococcus aureus bacteremia (SAB) is associated with a 90-day mortality of 28-34%. Many SAB-patients (7.8-39%) have a secondary S. aureus bacteriuria (SABU) mainly without symptoms of a urinary tract infection. Due to high morbidity and mortality, there is an interest in rapid detection of S. aureus bacteremia. Here, we compared a rapid nucleic acid amplification test (NAAT) with conventional culture to detect S. aureus in urine and to identify cases with increased risk for SAB.

Methods: In a cross-sectional study, we assessed urine samples (mid-stream, clean catch and catheter urine) of patients with SAB and bacteremia other than SAB (non-SAB). Urine samples were collected ± 3 days to the collection of the positive blood culture and were cultured on a set of selective and non-selective agar plates. NAAT was performed using a commercial test (Xpert® SA Nasal Complete G3, Cepheid) from a sterile swab soaked in urine.

Results: We included samples from 100 patients (68% male, median age: 67.4 years) with SAB and 20 patients (75% male, median age: 65.84 years) with non-SAB. The sensitivity of detecting SAB from urine samples was 47% (specificity: 90%) for NAAT, when applying a Ct-value of ≤ 37.4 for positive results. Urine culture had a sensitivity of 25% and a specificity of 95%. Molecular and culture methods showed a moderate agreement (80%, Cohens kappa: 0.55).

Conclusion: NAAT from urine has a higher sensitivity than culture in patients with SAB and could potentially identify cases with increased risk for SAB. Future studies should investigate whether this characteristic could translate into a clinical benefit through rapid detection of SAB.

目的:金黄色葡萄球菌菌血症(SAB)的 90 天死亡率为 28-34%。许多 SAB 患者(7.8%-39%)有继发性金黄色葡萄球菌菌尿(SABU),主要没有尿路感染症状。由于发病率和死亡率较高,人们对快速检测金黄色葡萄球菌菌血症很感兴趣。在此,我们比较了快速核酸扩增检验(NAAT)与传统培养法,以检测尿液中的金黄色葡萄球菌,并确定 SAB 风险增加的病例:在一项横断面研究中,我们对 SAB 患者和 SAB 以外的菌血症(非 SAB)患者的尿液样本(中段尿、清洁接尿和导管尿)进行了评估。尿液样本在血液培养阳性后 3 天内采集,并在一组选择性和非选择性琼脂平板上进行培养。使用商用检测试剂(Xpert® SA Nasal Complete G3,Cepheid)对浸泡在尿液中的无菌拭子进行 NAAT 检测:我们采集了 100 名 SAB 患者(68% 为男性,中位年龄为 67.4 岁)和 20 名非 SAB 患者(75% 为男性,中位年龄为 65.84 岁)的样本。当阳性结果的 Ct 值小于 37.4 时,NAAT 从尿液样本中检测 SAB 的灵敏度为 47%(特异性:90%)。尿培养的灵敏度为 25%,特异性为 95%。分子法和培养法显示出中等程度的一致性(80%,Cohens kappa:0.55):结论:在 SAB 患者中,尿液 NAAT 的灵敏度高于培养,有可能识别出 SAB 风险增加的病例。未来的研究应探讨这一特性是否能通过快速检测 SAB 转化为临床益处。
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引用次数: 0
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European Journal of Clinical Microbiology & Infectious Diseases
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