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Pharmacokinetics and pharmacodynamics of bacteriophage therapy: a review with a focus on multidrug-resistant Gram-negative bacterial infections. 噬菌体疗法的药代动力学和药效学:以耐多药革兰氏阴性菌感染为重点的综述。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-07-29 DOI: 10.1128/cmr.00044-24
Maria Siopi, Dimitrios Skliros, Paschalis Paranos, Nikoletta Koumasi, Emmanouil Flemetakis, Spyros Pournaras, Joseph Meletiadis

SUMMARYDespite the early recognition of their therapeutic potential and the current escalation of multidrug-resistant (MDR) pathogens, the adoption of bacteriophages into mainstream clinical practice is hindered by unfamiliarity with their basic pharmacokinetic (PK) and pharmacodynamic (PD) properties, among others. Given the self-replicative nature of bacteriophages in the presence of host bacteria, the adsorption rate, and the clearance by the host's immunity, their PK/PD characteristics cannot be estimated by conventional approaches, and thus, the introduction of new considerations is required. Furthermore, the multitude of different bacteriophage types, preparations, and treatment schedules impedes drawing general conclusions on their in vivo PK/PD features. Additionally, the drawback of acquired bacteriophage resistance of MDR pathogens with clinical and environmental implications should be taken into consideration. Here, we provide an overview of the current state of the field of PK and PD of bacteriophage therapy with a focus on its application against MDR Gram-negative infections, highlighting the potential knowledge gaps and the challenges in translation from the bench to the bedside. After reviewing the in vitro PKs and PDs of bacteriophages against the four major MDR Gram-negative pathogens, Klebsiella pneumoniae, Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Escherichia coli, specific data on in vivo PKs (tissue distribution, route of administration, and basic PK parameters in animals and humans) and PDs (survival and reduction of bacterial burden in relation to the route of administration, timing of therapy, dosing regimens, and resistance) are summarized. Currently available data merit close scrutiny, and optimization of bacteriophage therapy in the context of a better understanding of the underlying PK/PD principles is urgent to improve its therapeutic effect and to minimize the occurrence of bacteriophage resistance.

摘要尽管噬菌体的治疗潜力很早就得到了认可,而且目前耐多药(MDR)病原体不断增加,但由于不熟悉噬菌体的基本药代动力学(PK)和药效学(PD)等特性,噬菌体在主流临床实践中的应用受到了阻碍。鉴于噬菌体在宿主细菌存在下的自我复制特性、吸附率以及宿主免疫力的清除率,其 PK/PD 特性无法用传统方法估算,因此需要引入新的考虑因素。此外,由于噬菌体类型、制剂和治疗时间各不相同,因此无法对其体内 PK/PD 特征得出一般性结论。此外,还应考虑到 MDR 病原体对噬菌体产生耐药性的弊端对临床和环境的影响。在此,我们概述了噬菌体疗法的 PK 和 PD 领域的现状,重点介绍了其在治疗革兰氏阴性耐药菌感染方面的应用,并强调了在从实验室到临床转化过程中可能存在的知识差距和挑战。在回顾了噬菌体针对四种主要 MDR 革兰氏阴性病原体(肺炎克雷伯氏菌、鲍曼不动杆菌复合体、铜绿假单胞菌和大肠埃希菌)的体外 PKs 和 PDs 之后,总结了体内 PKs(组织分布、给药途径、动物和人类的基本 PK 参数)和 PDs(存活率和细菌负荷的减少与给药途径、治疗时机、给药方案和耐药性的关系)的具体数据。目前可用的数据值得仔细研究,当务之急是在更好地了解基本 PK/PD 原理的基础上优化噬菌体疗法,以提高其治疗效果并最大限度地减少噬菌体耐药性的发生。
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引用次数: 0
The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis. 角膜 HSV-1 感染和疱疹性基质角膜炎的免疫生物学。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-07-30 DOI: 10.1128/cmr.00006-24
Ferrin Antony, Divya Kinha, Anna Nowińska, Barry T Rouse, Amol Suryawanshi

SUMMARYHuman alphaherpesvirus 1 (HSV-1) is a highly successful neurotropic pathogen that primarily infects the epithelial cells lining the orofacial mucosa. After primary lytic replication in the oral, ocular, and nasal mucosal epithelial cells, HSV-1 establishes life-long latency in neurons within the trigeminal ganglion. Patients with compromised immune systems experience frequent reactivation of HSV-1 from latency, leading to virus entry in the sensory neurons, followed by anterograde transport and lytic replication at the innervated mucosal epithelial surface. Although recurrent infection of the corneal mucosal surface is rare, it can result in a chronic immuno-inflammatory condition called herpetic stromal keratitis (HSK). HSK leads to gradual vision loss and can cause permanent blindness in severe untreated cases. Currently, there is no cure or successful vaccine to prevent latent or recurrent HSV-1 infections, posing a significant clinical challenge to managing HSK and preventing vision loss. The conventional clinical management of HSK primarily relies on anti-virals to suppress HSV-1 replication, anti-inflammatory drugs (such as corticosteroids) to provide symptomatic relief from pain and inflammation, and surgical interventions in more severe cases to replace damaged cornea. However, each clinical treatment strategy has limitations, such as local and systemic drug toxicities and the emergence of anti-viral-resistant HSV-1 strains. In this review, we summarize the factors and immune cells involved in HSK pathogenesis and highlight alternate therapeutic strategies for successful clinical management of HSK. We also discuss the therapeutic potential of immunoregulatory cytokines and immunometabolism modulators as promising HSK therapies against emerging anti-viral-resistant HSV-1 strains.

摘要人类α疱疹病毒 1(HSV-1)是一种非常成功的神经性病原体,主要感染口腔粘膜上皮细胞。在口腔、眼部和鼻腔粘膜上皮细胞中进行初级溶解复制后,HSV-1 会在三叉神经节内的神经元中潜伏终身。免疫系统受损的患者会经常从潜伏期重新激活 HSV-1,导致病毒进入感觉神经元,然后在受支配的粘膜上皮细胞表面进行逆行运输和溶解复制。虽然角膜粘膜表面的复发性感染很少见,但它会导致一种慢性免疫炎症,即疱疹性基质角膜炎(HSK)。HSK 会导致视力逐渐下降,严重的患者如果不及时治疗,可能会永久失明。目前,还没有治疗方法或成功的疫苗来预防潜伏或复发的 HSV-1 感染,这给治疗 HSK 和预防视力丧失带来了巨大的临床挑战。HSK的传统临床治疗主要依靠抗病毒药物来抑制HSV-1的复制,使用抗炎药物(如皮质类固醇激素)来缓解疼痛和炎症症状,在病情较重的病例中还需要进行手术治疗,以更换受损的角膜。然而,每种临床治疗策略都有其局限性,如局部和全身药物毒性以及抗病毒 HSV-1 株的出现。在这篇综述中,我们总结了参与 HSK 发病机制的因素和免疫细胞,并强调了成功临床治疗 HSK 的替代治疗策略。我们还讨论了免疫调节细胞因子和免疫代谢调节剂作为HSK疗法的治疗潜力,以对抗新出现的抗病毒HSV-1毒株。
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引用次数: 0
Streptococcus dysgalactiae subsp. equisimilis infection and its intersection with Streptococcus pyogenes. 赤痢链球菌马氏亚种感染及其与化脓性链球菌的交叉感染。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-06-10 DOI: 10.1128/cmr.00175-23
Ouli Xie, Mark R Davies, Steven Y C Tong

SUMMARYStreptococcus dysgalactiae subsp. equisimilis (SDSE) is an increasingly recognized cause of disease in humans. Disease manifestations range from non-invasive superficial skin and soft tissue infections to life-threatening streptococcal toxic shock syndrome and necrotizing fasciitis. Invasive disease is usually associated with co-morbidities, immunosuppression, and advancing age. The crude incidence of invasive disease approaches that of the closely related pathogen, Streptococcus pyogenes. Genomic epidemiology using whole-genome sequencing has revealed important insights into global SDSE population dynamics including emerging lineages and spread of anti-microbial resistance. It has also complemented observations of overlapping pathobiology between SDSE and S. pyogenes, including shared virulence factors and mobile gene content, potentially underlying shared pathogen phenotypes. This review provides an overview of the clinical and genomic epidemiology, disease manifestations, treatment, and virulence determinants of human infections with SDSE with a particular focus on its overlap with S. pyogenes. In doing so, we highlight the importance of understanding the overlap of SDSE and S. pyogenes to inform surveillance and disease control strategies.

摘要赤痢链球菌马氏亚种(SDSE)越来越多地被认为是人类疾病的诱因。疾病表现从非侵袭性表皮和软组织感染到危及生命的链球菌中毒性休克综合症和坏死性筋膜炎。侵袭性疾病通常与并发症、免疫抑制和年龄增长有关。侵袭性疾病的粗发病率接近与之密切相关的病原体化脓性链球菌。使用全基因组测序的基因组流行病学揭示了全球 SDSE 种群动态的重要信息,包括新出现的品系和抗微生物耐药性的传播。它还补充了对 SDSE 和化脓性链球菌之间重叠病理生物学的观察,包括共享毒力因子和移动基因内容,这可能是共享病原体表型的基础。本综述概述了人类感染 SDSE 的临床和基因组流行病学、疾病表现、治疗和毒力决定因素,尤其关注其与化脓性链球菌的重叠。在此过程中,我们强调了了解 SDSE 与化脓性链球菌重叠的重要性,以便为监测和疾病控制策略提供依据。
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引用次数: 0
HIV-associated cancers and lymphoproliferative disorders caused by Kaposi sarcoma herpesvirus and Epstein-Barr virus. 由卡波济肉瘤疱疹病毒和 Epstein-Barr 病毒引起的艾滋病毒相关癌症和淋巴增生性疾病。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-06-20 DOI: 10.1128/cmr.00022-23
Kathryn A Lurain, Ramya Ramaswami, Laurie T Krug, Denise Whitby, Joseph M Ziegelbauer, Hao-Wei Wang, Robert Yarchoan

SUMMARYWithin weeks of the first report of acquired immunodeficiency syndrome (AIDS) in 1981, it was observed that these patients often had Kaposi sarcoma (KS), a hitherto rarely seen skin tumor in the USA. It soon became apparent that AIDS was also associated with an increased incidence of high-grade lymphomas caused by Epstein-Barr virus (EBV). The association of AIDS with KS remained a mystery for more than a decade until Kaposi sarcoma-associated herpesvirus (KSHV) was discovered and found to be the cause of KS. KSHV was subsequently found to cause several other diseases associated with AIDS and human immunodeficiency virus (HIV) infection. People living with HIV/AIDS continue to have an increased incidence of certain cancers, and many of these cancers are caused by EBV and/or KSHV. In this review, we discuss the epidemiology, virology, pathogenesis, clinical manifestations, and treatment of cancers caused by EBV and KSHV in persons living with HIV.

摘要在 1981 年首次报告获得性免疫缺陷综合症(艾滋病)后的几周内,人们发现这些患者通常患有卡波西肉瘤(KS),这是一种迄今为止在美国很少见的皮肤肿瘤。很快,人们发现艾滋病还与 Epstein-Barr 病毒(EBV)引起的高级别淋巴瘤发病率增加有关。十多年来,艾滋病与 KS 的关系一直是个谜,直到卡波西肉瘤相关疱疹病毒(KSHV)被发现并被认为是 KS 的病因。随后又发现 KSHV 可导致其他几种与艾滋病和人类免疫缺陷病毒(HIV)感染相关的疾病。艾滋病病毒感染者/艾滋病患者某些癌症的发病率持续上升,其中许多癌症是由 EBV 和/或 KSHV 引起的。在这篇综述中,我们将讨论 HIV 感染者中由 EBV 和 KSHV 引起的癌症的流行病学、病毒学、发病机制、临床表现和治疗。
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引用次数: 0
The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies. 太空中的人类微生物群:地球上菌群失调的相似之处、对长期太空飞行的影响以及可能的缓解策略。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-08-13 DOI: 10.1128/cmr.00163-22
Sofia Etlin, Julianna Rose, Luca Bielski, Claire Walter, Ashley S Kleinman, Christopher E Mason

SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.

摘要人体微生物群包括居住在人体各部位(如皮肤、鼻腔和胃肠道)内、上和周围的各种微生物群落。尽管研究仍在继续,但微生物群通过产生和改变代谢物和小分子对人体产生重大影响的观点已得到公认。微生物群组成的紊乱--菌群失调--也与各种不良健康后果有关。随着人类开始执行更长时间的太空任务,了解太空旅行的条件如何影响微生物群,进而影响宇航员的健康非常重要。本文将首先描述人类肠道微生物群的主要分类群及其相关代谢物的特征,然后讨论潜在的菌群失调和对健康的负面影响。文章还将详细介绍宇航员在太空飞行期间观察到的微生物变化,重点是肠道微生物群的组成以及致病菌的毒力和存活率。然后将分析如何通过饮食、运动和抗生素保护宇航员的健康免受不利微生物变化的影响,最后讨论航天器微生物群和太空微生物培养方法。这篇综述的影响至关重要,尤其是美国国家航空航天局正在实施的 "从月球到火星架构"(Moon to Mars Architecture),其中将包括数周或数月的太空生活和新的栖息地。
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引用次数: 0
mRNA-based HIV-1 vaccines. 基于 mRNA 的 HIV-1 疫苗。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-07-17 DOI: 10.1128/cmr.00041-24
Shamim Ahmed, Alon Herschhorn

SUMMARYThe success of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA vaccines to lessen/prevent severe COVID-19 opened new opportunities to develop RNA vaccines to fight other infectious agents. HIV-1 is a lentivirus that integrates into the host cell genome and persists for the lifetime of infected cells. Multiple mechanisms of immune evasion have posed significant obstacles to the development of an effective HIV-1 vaccine over the last four decades since the identification of HIV-1. Recently, attempts to address some of these challenges have led to multiple studies that manufactured, optimized, and tested, in different animal models, mRNA-based HIV-1 vaccines. Several clinical trials have also been initiated or are planned to start soon. Here, we review the current strategies applied to HIV-1 mRNA vaccines, discuss different targeting approaches, summarize the latest findings, and offer insights into the challenges and future of HIV-1 mRNA vaccines.

摘要 严重急性呼吸系统综合征冠状病毒 2 mRNA 疫苗在减轻/预防严重 COVID-19 方面取得了成功,这为开发 RNA 疫苗以对抗其他传染病病原体提供了新的机遇。HIV-1 是一种慢病毒,可整合到宿主细胞基因组中,并在受感染细胞的整个生命周期中持续存在。自发现 HIV-1 以来的 40 年中,多种免疫逃避机制对开发有效的 HIV-1 疫苗构成了重大障碍。最近,为了应对其中的一些挑战,人们开展了多项研究,制造、优化并在不同动物模型中测试基于 mRNA 的 HIV-1 疫苗。一些临床试验也已经启动或计划很快启动。在此,我们回顾了目前应用于 HIV-1 mRNA 疫苗的策略,讨论了不同的靶向方法,总结了最新发现,并对 HIV-1 mRNA 疫苗面临的挑战和未来提出了见解。
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引用次数: 0
Staphylococcus capitis: insights into epidemiology, virulence, and antimicrobial resistance of a clinically relevant bacterial species. 头癣葡萄球菌:对一种临床相关细菌的流行病学、毒性和抗菌药耐药性的深入研究。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-06-20 DOI: 10.1128/cmr.00118-23
Deborah M Crepin, Marie Chavignon, Paul O Verhoeven, Frédéric Laurent, Jérôme Josse, Marine Butin

SUMMARYStaphylococcus capitis is divided into two subspecies, S. capitis subsp. ureolyticus (renamed urealyticus in 1992; ATCC 49326) and S. capitis subsp. capitis (ATCC 27840), and fits with the archetype of clinically relevant coagulase-negative staphylococci (CoNS). S. capitis is a commensal bacterium of the skin in humans, which must be considered an opportunistic pathogen of interest particularly as soon as it is identified in a clinically relevant specimen from an immunocompromised patient. Several studies have highlighted the potential determinants underlying S. capitis pathogenicity, resistance profiles, and virulence factors. In addition, mobile genetic element acquisitions and mutations contribute to S. capitis genome adaptation to its environment. Over the past decades, antibiotic resistance has been identified for S. capitis in almost all the families of the currently available antibiotics and is related to the emergence of multidrug-resistant clones of high clinical significance. The present review summarizes the current knowledge concerning the taxonomic position of S. capitis among staphylococci, the involvement of this species in human colonization and diseases, the virulence factors supporting its pathogenicity, and the phenotypic and genomic antimicrobial resistance profiles of this species.

摘要头状葡萄球菌分为两个亚种:头状葡萄球菌尿解亚种(1992 年更名为尿解葡萄球菌;ATCC 49326)和头状葡萄球菌头状亚种(ATCC 27840),符合临床相关凝固酶阴性葡萄球菌(CoNS)的原型。毛囊炎葡萄球菌是人类皮肤的共生细菌,一旦在免疫力低下患者的临床相关标本中发现这种细菌,就必须将其视为机会性病原体。一些研究强调了毛囊虫致病性、抗药性特征和毒力因子的潜在决定因素。此外,移动遗传因子的获得和突变也有助于毛滴虫基因组对环境的适应。在过去的几十年中,已发现毛滴虫对几乎所有目前可用的抗生素家族都具有抗药性,这与具有高度临床意义的多重耐药克隆的出现有关。本综述总结了当前关于头孢霉菌在葡萄球菌中的分类地位、该菌种在人类定植和疾病中的参与、支持其致病性的毒力因素以及该菌种的表型和基因组抗菌药耐药性概况的知识。
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引用次数: 0
Vaccines and monoclonal antibodies to prevent healthcare-associated bacterial infections. 预防医疗相关细菌感染的疫苗和单克隆抗体。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-08-09 DOI: 10.1128/cmr.00160-22
Léo Sauvat, Paul O Verhoeven, Julie Gagnaire, Philippe Berthelot, Stéphane Paul, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon

SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridioides difficile, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.

摘要医疗相关感染(HAIs)是公共卫生的一个负担,其发病率和死亡率都很高。抗菌药耐药性潜力高的病原体,如 ESKAPE 病原体(粪肠球菌、金黄色葡萄球菌、肺炎克雷伯氏菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌)和难辨梭状芽胞杆菌是大多数 HAIs 的罪魁祸首。尽管实施了感染预防和控制干预措施,但在全球范围内,HAIs 的发病率仍保持稳定,而且主要是由内源性病原体引起的。不可否认,除了感染预防和控制措施外,还需要采取主动或被动免疫的预防方法。高危人群(老年人、免疫力低下的慢性病患者)和医护人员是重点关注对象。除了接触医院环境外,医疗程序和特定干预措施也有可能导致 HAIs。疫苗或单克隆抗体可被视为具有吸引力的预防 HAIs 的方法。在这篇综述中,我们概述了为预防主要细菌性 HAIs 病原体而进行临床开发的疫苗和单克隆抗体。基于目前的知识水平,我们探讨了通过这些方法改善预防效果所面临的挑战和未来前景。
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引用次数: 0
Practical Guidance for Clinical Microbiology Laboratories: Updated guidance for processing respiratory tract samples from people with cystic fibrosis. 临床微生物实验室实用指南》:处理囊性纤维化患者呼吸道样本的最新指南。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-12 Epub Date: 2024-08-19 DOI: 10.1128/cmr.00215-21
Lisa Saiman, Valerie Waters, John J LiPuma, Lucas R Hoffman, Kevin Alby, Sean X Zhang, Yvonne C Yau, Damian G Downey, Isabelle Sermet-Gaudelus, Jean-Philippe Bouchara, Timothy J Kidd, Scott C Bell, A Whitney Brown

SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., Stenotrophomonas maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of S. aureus, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., S. maltophilia, Inquilinus, Achromobacter, Ralstonia, and Pandoraea species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.

摘要 本指南提出了临床微生物实验室处理囊性纤维化患者 (pwCF) 呼吸道样本的建议。适当处理呼吸道样本对于检测细菌和真菌病原体、指导治疗、监测囊性纤维化 (CF) 病原体的流行病学以及评估治疗干预措施至关重要。得益于囊性纤维化跨膜传导调节剂的治疗,囊性纤维化患者的健康状况有所改善,但自发排痰的囊性纤维化患者却越来越少。因此,痰样本的采集量减少了,而口咽和支气管肺泡灌洗液样本等其他类型呼吸道样本的采集量却增加了。为了优化微生物的检测,包括铜绿假单胞菌、金黄色葡萄球菌、流感嗜血杆菌、伯克霍尔德氏菌头孢菌素复合体,以及其他不常见的非乳糖发酵革兰氏阴性杆菌,如嗜血杆菌、恶性链球菌等、对于所有类型的呼吸道样本,包括肺移植后从 pwCF 获得的样本,建议使用非选择性和选择性培养基来培养酵母菌和丝状真菌。对于检测、鉴定和报告金黄色葡萄球菌小菌落变异(SCVs)的实验室方法,目前还没有达成共识的建议,尽管针对 SCVs 潜在临床影响的研究正在进行中。建议准确鉴定不常见的革兰氏阴性杆菌,例如:S. maltopholia、Inquilinus、Achromobacter、Ralstonia 和 Pandoraea 菌种,以及酵母菌和丝状真菌,以了解它们的流行病学和临床影响。
{"title":"Practical Guidance for Clinical Microbiology Laboratories: Updated guidance for processing respiratory tract samples from people with cystic fibrosis.","authors":"Lisa Saiman, Valerie Waters, John J LiPuma, Lucas R Hoffman, Kevin Alby, Sean X Zhang, Yvonne C Yau, Damian G Downey, Isabelle Sermet-Gaudelus, Jean-Philippe Bouchara, Timothy J Kidd, Scott C Bell, A Whitney Brown","doi":"10.1128/cmr.00215-21","DOIUrl":"10.1128/cmr.00215-21","url":null,"abstract":"<p><p>SUMMARYThis guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Haemophilus influenzae</i>, and <i>Burkholderia cepacia</i> complex; other less common non-lactose fermenting Gram-negative bacilli, e.g., <i>Stenotrophomonas maltophilia</i>, <i>Inquilinus</i>, <i>Achromobacter</i>, <i>Ralstonia</i>, and <i>Pandoraea</i> species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of <i>S. aureus</i>, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g., <i>S. maltophilia</i>, <i>Inquilinus</i>, <i>Achromobacter</i>, <i>Ralstonia</i>, and <i>Pandoraea</i> species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0021521"},"PeriodicalIF":19.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The emerging challenge of Enterococcus faecalis endocarditis after transcatheter aortic valve implantation: time for innovative treatment approaches. 经导管主动脉瓣植入术后新出现的粪肠球菌心内膜炎挑战:创新治疗方法的时机已到。
IF 19 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-09-05 DOI: 10.1128/cmr.00168-23
Jaclyn A Cusumano, Andreas P Kalogeropoulos, Mathieu Le Provost, Nicolas R Gallo, Steven M Levine, Thomas Inzana, Aikaterini Papamanoli

SUMMARYInfective endocarditis (IE) is a life-threatening infection that has nearly doubled in prevalence over the last two decades due to the increase in implantable cardiac devices. Transcatheter aortic valve implantation (TAVI) is currently one of the most common cardiac procedures. TAVI usage continues to exponentially rise, inevitability increasing TAVI-IE. Patients with TAVI are frequently nonsurgical candidates, and TAVI-IE 1-year mortality rates can be as high as 74% without valve or bacterial biofilm removal. Enterococcus faecalis, a historically less common IE pathogen, is the primary cause of TAVI-IE. Treatment options are limited due to enterococcal intrinsic resistance and biofilm formation. Novel approaches are warranted to tackle current therapeutic gaps. We describe the existing challenges in treating TAVI-IE and how available treatment discovery approaches can be combined with an in silico "Living Heart" model to create solutions for the future.

摘要感染性心内膜炎(IE)是一种威胁生命的感染,由于植入式心脏设备的增加,其发病率在过去二十年中几乎翻了一番。经导管主动脉瓣植入术(TAVI)是目前最常见的心脏手术之一。经导管主动脉瓣植入术的使用率继续呈指数增长,不可避免地增加了经导管主动脉瓣植入术的创伤。TAVI 患者通常都是非手术候选者,如果不清除瓣膜或细菌生物膜,TAVI-IE 1 年死亡率可高达 74%。粪肠球菌是一种历史上较少见的 IE 病原,是导致 TAVI-IE 的主要原因。由于肠球菌的内在耐药性和生物膜的形成,治疗方案十分有限。需要采用新方法来解决目前的治疗空白。我们介绍了治疗 TAVI-IE 的现有挑战,以及如何将现有的治疗发现方法与硅学 "活体心脏 "模型相结合,为未来创造解决方案。
{"title":"The emerging challenge of <i>Enterococcus faecalis</i> endocarditis after transcatheter aortic valve implantation: time for innovative treatment approaches.","authors":"Jaclyn A Cusumano, Andreas P Kalogeropoulos, Mathieu Le Provost, Nicolas R Gallo, Steven M Levine, Thomas Inzana, Aikaterini Papamanoli","doi":"10.1128/cmr.00168-23","DOIUrl":"10.1128/cmr.00168-23","url":null,"abstract":"<p><p>SUMMARYInfective endocarditis (IE) is a life-threatening infection that has nearly doubled in prevalence over the last two decades due to the increase in implantable cardiac devices. Transcatheter aortic valve implantation (TAVI) is currently one of the most common cardiac procedures. TAVI usage continues to exponentially rise, inevitability increasing TAVI-IE. Patients with TAVI are frequently nonsurgical candidates, and TAVI-IE 1-year mortality rates can be as high as 74% without valve or bacterial biofilm removal. <i>Enterococcus faecalis,</i> a historically less common IE pathogen, is the primary cause of TAVI-IE. Treatment options are limited due to enterococcal intrinsic resistance and biofilm formation. Novel approaches are warranted to tackle current therapeutic gaps. We describe the existing challenges in treating TAVI-IE and how available treatment discovery approaches can be combined with an <i>in silico</i> \"Living Heart\" model to create solutions for the future.</p>","PeriodicalId":10378,"journal":{"name":"Clinical Microbiology Reviews","volume":" ","pages":"e0016823"},"PeriodicalIF":19.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132040","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}
引用次数: 0
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Clinical Microbiology Reviews
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