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Profiling of circulating immune factors and host-derived extracellular vesicles in response to bacterial or malaria acute fever. 循环免疫因子和宿主来源的细胞外囊泡对细菌性或疟疾急性发烧的反应。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-19 DOI: 10.1007/s15010-025-02694-7
Natalia Tiberti, Giulia Bertoli, Cristina Mazzi, Elisabetta Vezzelli, Serena Zanzoni, Francesca Alladio, Zeno Bisoffi, Francesca Tamarozzi, Chiara Piubelli, Dora Buonfrate, Federico Giovanni Gobbi

The misdiagnosis of acute febrile illness (AFI) aetiology is associated with antibiotic overuse and improper patient management. To develop novel strategies, a more comprehensive understanding of the pathophysiological mechanisms underlying the early response to different causes of fever is essential.Here we examined the host response to AFI, through the retrospective investigation of serum samples from febrile patients with bacterial infection (n = 52) or malaria (n = 73). The systemic levels of CXCL10, IFNγ, IL-2, IL-4, IL-6, IL-8, procalcitonin (PCT), TRAIL, ICAM-1, VCAM-1, osteopontin, TNFα, MMP-2 and MMP-9 were measured by multiplex immunoassays, while the relative abundance of 37 different surface markers of circulating extracellular vesicles (EVs) was determined using the MACSplex kit (Miltenyi Biotec).Markers of endothelial activation (CD29+, CD62P+, CD9+ EVs) and immune cell migration (MMP-2 and MMP-9) appeared elevated in bacterial AFI (q-value < 0.05). Mediators associated with antigen recognition (CD8+, CD81+, HLA-DR/DP/DQ+ EVs) and cytokine storm (IFNγ, CXCL10, TNFα) were instead prominent in malaria infection (q-value < 0.005). Interestingly, HLA-DR/DP/DQ+ EVs distinguished between bacterial and malaria AFI with area under the ROC curve (AUC) of 0.87, not significantly different from platelets' AUC (0.92), which was the best individual discriminator.Our results showed different biological processes as associated with bacterial and malaria AFI, paving the way for the identification of novel potential markers for a timely and reliable AFI diagnosis. The study also provides novel insights on the potential role of EVs as mediators of pro-inflammatory signalling during acute fever, which should be investigated more comprehensively in vitro.

急性发热性疾病(AFI)病因的误诊与抗生素过度使用和患者管理不当有关。为了制定新的策略,更全面地了解对不同发热原因的早期反应的病理生理机制是必不可少的。在这里,我们通过回顾性调查细菌感染(n = 52)或疟疾(n = 73)发热患者的血清样本,研究了宿主对AFI的反应。采用多重免疫分析法检测CXCL10、IFNγ、IL-2、IL-4、IL-6、IL-8、降钙素原(PCT)、TRAIL、ICAM-1、VCAM-1、骨桥蛋白、TNFα、MMP-2和MMP-9的系统水平,采用MACSplex试剂盒(Miltenyi Biotec)检测循环细胞外囊泡(EVs) 37种不同表面标志物的相对丰度。细菌AFI中内皮细胞激活(CD29+、CD62P+、CD9+ EVs)和免疫细胞迁移(MMP-2和MMP-9)标志物升高(q值+、CD81+、HLA-DR/DP/DQ+ EVs),而细胞因子风暴(IFNγ、CXCL10、TNFα)在疟疾感染中表现突出(q值+ EVs区分细菌和疟疾AFI的ROC曲线下面积(AUC)为0.87,与血小板AUC(0.92)无显著差异,是最佳的个体鉴别指标。我们的研究结果显示了不同的生物学过程与细菌和疟疾AFI相关,为鉴定新的潜在标志物以及时可靠地诊断AFI铺平了道路。该研究还为ev作为急性发热时促炎信号介质的潜在作用提供了新的见解,这需要在体外进行更全面的研究。
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引用次数: 0
Language matters: the case of "septic arthritis". 语言很重要:“脓毒性关节炎”的案例。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-18 DOI: 10.1007/s15010-025-02680-z
Gerd Fätkenheuer
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引用次数: 0
Otogenic meningitis in children. 儿童耳源性脑膜炎。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-17 DOI: 10.1007/s15010-025-02690-x
Laura Lempinen, Riste Saat, Anu Laulajainen-Hongisto, Antti A Aarnisalo, Tea Nieminen, Jussi Jero

Purpose: Otogenic meningitis is a rare but potentially life-threatening intracranial complication of otitis media (OM). Our aim was to study the incidence of childhood otogenic meningitis and to compare clinical presentation, causative pathogens, diagnostics, treatment, and outcome of otogenic versus non-otogenic meningitis.

Methods: Charts were reviewed for 47 children admitted to our tertiary center with bacterial meningitis (BM) between 2010 and 2020. Otoscopy and/or imaging were used to determine the otogenic meningitis ratio and the mean annual incidence was calculated.

Results: Eight (17%) of the 47 BM cases were otogenic [5 males; median age 1.3 years (range 2 months to 16 years)]. The otogenic meningitis incidence was 0.3/100 000/year. The classic triad of fever, altered level of consciousness, and meningeal irritation was more common in children with otogenic meningitis (50%, 4/8) than without OM (14%, 5/36) (P = 0.042). Streptococcus pneumoniae was a more common pathogen in children with OM (88%, 7/8) than without OM (14%, 4/29) (P < 0.001), whereas Neisseria meningitidis infection occurred only in children without OM (41%, 12/29) (P = 0.036). Neurological sequelae at discharge were present in 3 (38%) children with OM. Deafness was diagnosed in two children, both with otogenic backgrounds. Three children showed long-term sequelae: 2 had deafness (aged < 2 years) and 1 had aphasia/dysphasia.

Conclusion: The incidence of otogenic meningitis was 0.3/100 000/year, with S. pneumoniae the most common causative pathogen. Deafness was the most common long-term sequela and occurred only in children with otogenic meningitis.

目的:耳源性脑膜炎是一种罕见但可能危及生命的颅内并发症中耳炎(OM)。我们的目的是研究儿童耳源性脑膜炎的发病率,并比较耳源性脑膜炎与非耳源性脑膜炎的临床表现、致病病原体、诊断、治疗和结果。方法:回顾性分析2010 ~ 2020年我院收治的细菌性脑膜炎(BM)患儿47例。耳镜检查和/或影像学检查用于确定耳源性脑膜炎的发病率,并计算平均年发病率。结果:47例BM中8例(17%)为耳源性[男性5例;中位年龄1.3岁(范围2个月至16岁)。耳源性脑膜炎发病率为0.3/10万/年。发热、意识水平改变和脑膜刺激的典型三联征在耳源性脑膜炎患儿中(50%,4/8)比无OM患儿(14%,5/36)更为常见(P = 0.042)。结论:耳源性脑膜炎的发病率为0.3/10万/年,其中肺炎链球菌为最常见的致病菌。耳聋是最常见的长期后遗症,仅发生在耳源性脑膜炎患儿中。
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引用次数: 0
Is short-course antibiotic therapy as safe and effective as long-course therapy after surgery for complicated appendicitis? A systematic review and meta-analysis. 复杂性阑尾炎术后短期抗生素治疗与长期抗生素治疗一样安全有效吗?系统回顾和荟萃分析。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-14 DOI: 10.1007/s15010-025-02693-8
Kai Lu, Shilong Shu, Xuefeng Peng, Faqiang Zhang, Yong Cheng, Hua Yang

Background: Short-course antibiotic (SCA) therapy after appendectomy for complicated appendicitis (CA) has gained increasing attention, but its safety and efficacy remain insufficiently supported by meta-analyses. This study aimed to evaluate whether SCA therapy is as safe and effective as conventional long-course antibiotic (LCA) therapy following appendectomy for CA.

Methods: A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) and observational studies comparing different durations of postoperative antibiotic therapy for CA. Data were analyzed using RevMan 5.3 for meta-analysis, and the GRADE approach was applied to assess the quality of evidence for key outcomes.

Results: Four RCTs and nine observational studies involving 3,251 patients were included. The meta-analysis revealed no significant increase in the risk of surgical site infection (SSI) (RR = 1.19, 95% CI: 0.52 to 2.73, P = 0.67, low-quality evidence) or intra-abdominal abscess (IAA) (RR = 1.18, 95% CI: 0.92 to 1.51, P = 0.19, moderate-quality evidence) with less than 3-day SCA therapy compared to LCA therapy. Secondary outcomes showed no significant differences between the two regimens (moderate to very-low quality evidence). However, SCA therapy was associated with a shorter length of hospital stay (low-quality evidence).

Conclusion: For patients with CA, less than 3-day SCA therapy does not increase the risk of SSI or IAA. Moreover, reducing the duration of antibiotic use may help minimize unnecessary antibiotic consumption.

背景:复杂性阑尾炎(CA)阑尾切除术后短期抗生素(SCA)治疗越来越受到关注,但其安全性和有效性仍未得到meta分析的充分支持。本研究旨在评估SCA治疗是否与传统的长疗程抗生素(LCA)治疗一样安全有效。我们进行了全面的文献检索,以确定比较CA术后不同抗生素治疗时间的随机对照试验(rct)和观察性研究。使用RevMan 5.3对数据进行荟萃分析,并采用GRADE方法评估关键结局的证据质量。结果:纳入4项随机对照试验和9项观察性研究,涉及3251例患者。荟萃分析显示,与LCA治疗相比,少于3天的SCA治疗没有显著增加手术部位感染(SSI) (RR = 1.19, 95% CI: 0.52至2.73,P = 0.67,低质量证据)或腹腔脓肿(IAA) (RR = 1.18, 95% CI: 0.92至1.51,P = 0.19,中等质量证据)的风险。次要结果显示两种方案之间无显著差异(中度至极低质量证据)。然而,SCA治疗与较短的住院时间相关(低质量证据)。结论:对于CA患者,少于3天的SCA治疗不会增加SSI或IAA的风险。此外,减少抗生素使用的持续时间可能有助于减少不必要的抗生素消耗。
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引用次数: 0
Evaluating Seqstant LiveGene Analysis in real-time assessment of metagenomic next-generation sequencing (mNGS) data from respiratory samples. 评估Seqstant LiveGene分析在实时评估呼吸样本宏基因组下一代测序(mNGS)数据中的应用。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-11 DOI: 10.1007/s15010-025-02665-y
Sébastien Boutin, Sabrina Klein, Gerold Untergasser, Tobias P Loka, Suzan Jakob, Yasemin Caf, Elham Khatamzas, Ludwig Knabl, Georg Wrettos, Henri Knobloch, Dennis Nurjadi

Background: The detection of pathogens causing infections by conventional diagnostic methods can be challenging and next-generation sequencing (NGS) technology offers a promising alternative method. In this study, we evaluated the performance of real-time metagenomic next-generation sequencing (rt-mNGS) for the detection of pathogens in respiratory samples.

Method: We used rt-mNGS, using the Seqstant LiveGene Analysis platform, on 335 respiratory samples in comparison to conventional culture results.

Results: We observed an overall good concordance in 71.64% (240/335) of the methods. The rt-mNGS outperformed the gold standard culture in 16.12% (54/335) of the samples, while the culture was superior in detecting the clinically relevant pathogen in 12.24% (41/335) of the samples. The non-inferiority of rt-mNGS was statistically significant (δ = 10, α = 0.05, 1 - β = 0.8). We also observed that the real-time analysis of NGS data is beneficial in obtaining reliable, timely results, as the initial report at cycle 46 exhibits a Positive Predictive Value (PPV) of 93.75% at the species-level with a sensitivity of 32.09%.

Conclusion: Overall, our study showed the non-inferiority of rt-mNGS compared to the standard-of-care microbiology for respiratory samples with statistical significance. Moreover, the rt-mNGS method exhibited superior sensitivity and superior overall performance. It also uniquely detected certain organisms that are typically hard to culture. However, rt-mNGS reported a higher number of false positives and faced limitations in detecting Aspergillus spp. In conclusion, the study highlights the potential of rt-mNGS as a powerful tool in clinical diagnostics of respiratory infections and beyond.

背景:通过传统的诊断方法检测引起感染的病原体是具有挑战性的,而下一代测序(NGS)技术提供了一种有前途的替代方法。在这项研究中,我们评估了实时宏基因组下一代测序(rt-mNGS)检测呼吸道样本中病原体的性能。方法:利用Seqstant LiveGene分析平台,对335份呼吸道样本进行rt-mNGS检测,并与常规培养结果进行比较。结果:71.64%(240/335)的方法总体一致性较好。rt-mNGS在16.12%(54/335)的样品中优于金标准培养,在12.24%(41/335)的样品中优于金标准培养。rt-mNGS的非劣效性具有统计学意义(δ = 10, α = 0.05, 1 - β = 0.8)。我们还发现,NGS数据的实时分析有助于获得可靠、及时的结果,因为第46周期的初始报告在物种水平上的阳性预测值(PPV)为93.75%,灵敏度为32.09%。结论:总体而言,我们的研究显示rt-mNGS与呼吸样本的标准护理微生物学相比具有非劣效性,具有统计学意义。此外,rt-mNGS方法表现出优越的灵敏度和综合性能。它还独特地检测到某些通常难以培养的生物体。然而,rt-mNGS报告的假阳性数量较高,并且在检测曲霉菌方面存在局限性。总之,该研究强调了rt-mNGS作为临床诊断呼吸道感染及其他疾病的强大工具的潜力。
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引用次数: 0
Endemic avian influenza landscape in Asia: sustained zoonotic risks. 亚洲地方性禽流感形势:持续的人畜共患风险。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-11 DOI: 10.1007/s15010-025-02681-y
Nitin Gupta, Martin P Grobusch, Jan Felix Drexler, José Ramón Paño-Pardo, Galadriel Pellejero-Sagastizabal, Sotirios Tsiodras, Aleksandra Barac, F-Xavier Lescure, Pikka Jokelainen

Avian influenza remains a persistent global health threat, with Asia at its epicentre due to dense poultry production, live bird markets, and cross-species interfaces with ducks and swine. Several pathogenic subtypes continue to cause recurrent zoonotic spillovers with varying human case fatality, reinforcing the region's role as a pandemic hotspot. Surveillance highlights the main key ecological drivers: sustained viral circulation in live bird markets, subclinical infection in domestic ducks, wild birds serving as reservoirs, and multiple species with dual receptors that can act as mixing vessels enabling reassortment. Recent events in the United States, where H5N1 has emerged in dairy cattle with viral RNA detectable in retail milk and human cases arising from both poultry and dairy cattle exposures, further demonstrate the capacity of these viruses to invade new mammalian hosts and the food chain. Advances in poultry vaccination and next-generation antivirals show promise but are constrained by antigenic drift, incomplete protection, logistical barriers, and uneven uptake. Human preparedness remains weakened by diagnostic delays, limited access to therapeutics, and fragmented surveillance. Mitigation requires regionally tailored, One Health-driven strategies, market regulation, duck vaccination, swine surveillance, and rapid therapeutic deployment, together with equitable access to tools and transparent international collaboration to reduce zoonotic risk and strengthen global pandemic readiness. This review synthesizes recent evidence on avian influenza virus infections in Asia, outlining zoonotic risks, key drivers, and mitigation strategies, and concludes that the sustained circulation of these viruses in poultry and wild birds continues to present significant challenges for animal health, public health, and pandemic preparedness, highlighting the importance of strengthened One Health surveillance and control measures.

禽流感仍然是一个持续存在的全球健康威胁,由于密集的家禽生产、活禽市场以及鸭和猪的跨物种接触,亚洲是其震中。几种致病亚型继续引起反复出现的人畜共患病外溢,造成不同的人间病死率,加强了该区域作为大流行热点的作用。监测突出了主要的生态驱动因素:活禽市场中持续的病毒循环,家鸭的亚临床感染,作为宿主的野鸟,以及具有双重受体的多种物种可以作为混合容器,从而实现重新组合。最近在美国发生的事件进一步表明,这些病毒有能力侵入新的哺乳动物宿主和食物链。在美国,在零售牛奶中发现H5N1型病毒,并在家禽和奶牛中发现病毒RNA。家禽疫苗接种和下一代抗病毒药物的进展显示出希望,但受到抗原漂移、保护不完全、后勤障碍和吸收不均匀的限制。由于诊断延误、获得治疗的机会有限以及监测不完整,人类的防范能力仍然被削弱。缓解需要根据地区情况量身定制、以“一种健康”为导向的战略、市场监管、鸭疫苗接种、猪监测和快速治疗部署,以及公平获得工具和透明的国际合作,以减少人畜共患病风险并加强全球大流行防范。本综述综合了亚洲禽流感病毒感染的最新证据,概述了人畜共患风险、主要驱动因素和缓解战略,并得出结论认为,这些病毒在家禽和野生鸟类中的持续传播继续对动物卫生、公共卫生和大流行防范构成重大挑战,强调了加强“同一个卫生”监测和控制措施的重要性。
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引用次数: 0
'Herpes simplex virus infection in a bipulmonary transplant recipient'. “双肺移植受者的单纯疱疹病毒感染”
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-10 DOI: 10.1007/s15010-025-02558-0
Miguel Mansilla-Polo, Daniel Martín-Torregrosa, Sara Becerril-Andrés, Javier López-Davia
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引用次数: 0
Editorial letter - Infection. : Asymptomatic bacteriuria in pregnancy: limitations of Registry-Based research. 社论:感染。妊娠期无症状细菌性尿症:基于登记研究的局限性。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-10 DOI: 10.1007/s15010-025-02688-5
Jon Dissing Sund, Nina Weis, Ellen Moseholm
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引用次数: 0
CanDRes: Exploring the Mutation Landscape of Candida and its Role in Antifungal Resistance. 念珠菌:探索念珠菌的突变景观及其在抗真菌耐药性中的作用。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-08 DOI: 10.1007/s15010-025-02686-7
Chandan Kumar, Anam Arshi, Anchal Yadav, Prashik Chavan, Susan Idicula-Thomas

Purpose: Candida spp. has emerged as major fungal pathogens, especially in immunocompromised individuals, posing significant challenges in clinical settings. Their growing prevalence and increasing resistance to antifungal agents underscore the urgent need for systematic investigation into resistance mechanisms. Constant monitoring of resistance-associated mutations is essential to mitigate drug resistance and develop effective therapeutic strategies.

Method: We developed CanDRes, a manually curated, open-access resource cataloging mutations linked to antifungal resistance in Candida spp. Mutations were systematically compiled from published literature, focusing on those identified in drug-resistant clinical isolates. Each entry was annotated with gene-level information, drug associations, organism specificity, resistance mechanisms, and evidence-based validation scores. 3D structures of mutant proteins were developed and are available for download from the CanDRes database.

Results: CanDRes encompasses 1053 unique mutations across 56 genes from drug-resistant strains of 13 Candida spp., assessed against 19 antifungal drugs. The database also includes resistance mechanisms, protein sequences, predicted 3D structural models, and mutation plots. These data provide a valuable foundation for understanding molecular resistance patterns and for guiding therapeutic decision-making.

Conclusion: Our study emphasizes the critical need to investigate antifungal resistance in Candida spp., which are among the most clinically challenging fungal pathogens. Understanding the mechanisms driving resistance to frontline antifungals can improve treatment strategies. CanDRes serves as a free and accessible resource for clinicians and researchers aiming to address antifungal resistance. Users can access CanDRes via https://candres.bicnirrh.res.in/ .

目的:念珠菌已经成为主要的真菌病原体,特别是在免疫功能低下的个体中,在临床环境中提出了重大挑战。它们日益流行,对抗真菌药物的耐药性也越来越强,因此迫切需要对其耐药机制进行系统研究。持续监测耐药性相关突变对于减轻耐药性和制定有效的治疗策略至关重要。方法:我们开发了CanDRes,这是一个人工编辑的、开放获取的资源,用于编目念珠菌菌株抗真菌耐药性相关的突变。我们从已发表的文献中系统地汇编了突变,重点是在耐药临床分离株中发现的突变。每个条目都附有基因水平信息、药物关联、生物体特异性、耐药机制和循证验证分数的注释。突变蛋白的三维结构被开发出来,并且可以从CanDRes数据库下载。结果:CanDRes包含来自13种念珠菌耐药菌株的56个基因的1053个独特突变,对19种抗真菌药物进行了评估。该数据库还包括抗性机制、蛋白质序列、预测的3D结构模型和突变图。这些数据为理解分子耐药模式和指导治疗决策提供了宝贵的基础。结论:我们的研究强调了研究念珠菌属抗真菌耐药性的迫切需要,念珠菌属是临床上最具挑战性的真菌病原体之一。了解对一线抗真菌药物产生耐药性的机制可以改善治疗策略。CanDRes为临床医生和研究人员提供免费和可访问的资源,旨在解决抗真菌耐药性问题。用户可以通过https://candres.bicnirrh.res.in/访问CanDRes。
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引用次数: 0
The infectome framework: linking polymicrobial ecology and biofilm dynamics to precision diagnostic approaches. 感染组框架:将多微生物生态学和生物膜动力学与精确诊断方法联系起来。
IF 3.6 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-07 DOI: 10.1007/s15010-025-02687-6
Reem Mahdi Saleh, Omar Mohammed Hassan

Chronic infections are a persistent global health problem and are frequently sustained by polymicrobial communities rather than by a single pathogen. This review brings together current evidence for the infectome concept, defined as the dynamic set of pathogenic or pathobiont taxa in the host, their shared functional capacities, and the interactions that connect them. We analyze how community-level processes promote persistence, cause diagnostic failure, and drive therapeutic resistance, with emphasis on multispecies biofilms, quorum sensing, horizontal gene transfer, metabolic cooperation, and immune modulation. We also highlight advances in multi-omics and computational integration that now permit high-resolution infectome profiling and reveal taxa and interspecies networks that are not captured by routine culture. Clinical examples such as periodontitis, bacterial vaginosis, chronic rhinosinusitis, device-associated infections, and recurrent urinary tract infections show the translational value of this shift. On the therapeutic side, we discuss infectome-informed options including antivirulence agents, biofilm-disrupting enzymes, bacteriophages and lysins, community-wide susceptibility-guided regimens, and microbiome-restoration strategies. Finally, we identify the main requirements for the field: standardized sampling and analytic workflows, reproducible infectome signatures linked to clinical outcomes, and trial designs able to capture ecological dynamics and meet regulatory expectations for community-targeted interventions. Adopting an infectome perspective can enable precision infectiology and reshape the management of chronic and recurrent infections.

慢性感染是一个持续存在的全球健康问题,经常由多种微生物群落而不是单一病原体造成。这篇综述汇集了感染组概念的现有证据,感染组被定义为宿主中病原或病原体分类群的动态集合,它们的共同功能能力,以及将它们联系起来的相互作用。我们分析了社区层面的过程如何促进持久性,导致诊断失败,并驱动治疗耐药性,重点是多物种生物膜,群体感应,水平基因转移,代谢合作和免疫调节。我们还强调了多组学和计算集成方面的进展,这些进展现在允许高分辨率的感染组分析,并揭示常规培养无法捕获的分类群和种间网络。临床实例如牙周炎、细菌性阴道病、慢性鼻窦炎、器械相关感染和复发性尿路感染显示了这种转变的转化价值。在治疗方面,我们讨论了感染信息选择,包括抗毒剂,生物膜破坏酶,噬菌体和溶酶,社区范围内的敏感性指导方案,以及微生物组恢复策略。最后,我们确定了该领域的主要要求:标准化采样和分析工作流程,与临床结果相关的可重复感染组特征,以及能够捕捉生态动态并满足社区目标干预的监管期望的试验设计。采用感染学的观点可以使精确的感染学和重塑慢性和复发性感染的管理。
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引用次数: 0
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