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Translation: Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10) 新冠肺炎诊疗方案(试行版10)
Q3 INFECTIOUS DISEASES Pub Date : 2023-01-25 DOI: 10.1097/im9.0000000000000112
In order to further strengthen the diagnosis and treatment of novel coronavirus infection (COVID-19), we revised the Diagnosis and Treatment Protocol for COVID-19 (Revised Trial Version 9) to Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10). 1. Etiological characteristics Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the β-genus coronaviruses. It has an envelope, and the virus particle is round or oval, with a diameter ranging 60–140 nm. It contains four structural proteins, namely, the spike (S) protein, the envelope (E) protein, the matrix protein (M) and the nucleoprotein (N) protein. The genome of SARS-CoV-2 is a single-stranded positive-sense RNA molecule with a total length of approximately 29.9 kb. The open reading frames contained within the genome are arranged in sequence as 5′-replicase (ORF1a/ORF1b)-S-ORF3a-ORF3b-E-M-ORF6-ORF7a-ORF7b-ORF8-N-ORF9a-ORF9b-ORF10–3′. The RNA genome is wrapped by the N protein, forming a nucleocapsid, a core structure of the virus particle, surrounded by lipid bilayer membrane, in which the S protein, the M protein and the N protein of SARS-CoV-2 are embedded. After invading the human respiratory tract, SARS-CoV-2 mainly relies on the receptor binding domain of the S protein on the virus cell surface to recognize the host cell receptor angiotensin-converting enzyme 2, and then interacts with the receptor, allowing the virus to enter host cells. During the epidemic and transmission of SARS-CoV-2 in the population, its genes have frequently shown mutations. When different subvariants or lineages of SARS-CoV-2 infect the human body simultaneously, these viruses might recombine, resulting in the emergence of recombinant virus strains. Certain mutations or recombinations will affect the biological characteristics of the virus. For instance, mutations of specific amino acids on the S protein enhance the affinity between SARS-CoV-2 and angiotensin-converting enzyme 2, and concomitantly the ability of the virus to replicate and spread between cells. Some amino acid mutations on the S protein will also increase viral immune escape from vaccines and reduce the cross-protection between different subvariants, resulting in breakthrough infections and a certain proportion of reinfections. As of the end of 2022, five variants of concern, namely, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529), have been designated by the World Health Organization. Compared with other variants of concern such as Delta, the transmissibility and immune escape ability of the Omicron variant, which emerged in the population in November 2021, have been significantly enhanced and the Omicron variant has promptly replaced the Delta variant as the dominant global epidemic variant since early 2022. Up to now, the five subvariants of Omicron (BA.1, BA.2, BA.3, BA.4 and BA.5) have successively evolved into 709 serial lineages, including 72 recombinant lineages. As SARS-C
为了进一步加强对新型冠状病毒感染(COVID-19)的诊断和治疗,我们将《COVID-19诊疗方案(修订试行版9)》修订为《COVID-19诊疗方案(试行版10)》。1. 严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)属于β属冠状病毒。它有一个包膜,病毒颗粒为圆形或椭圆形,直径在60-140纳米之间。它包含四种结构蛋白,即刺突(S)蛋白、包膜(E)蛋白、基质蛋白(M)和核蛋白(N)蛋白。SARS-CoV-2的基因组是一个单链正义RNA分子,全长约29.9 kb。基因组中包含的开放阅读框按顺序排列为5 ' -复制酶(ORF1a/ORF1b) -S-ORF3a-ORF3b-E-M-ORF6-ORF7a-ORF7b-ORF8-N-ORF9a-ORF9b-ORF10-3 '。RNA基因组被N蛋白包裹,形成一个核衣壳,这是病毒颗粒的核心结构,被脂质双层膜包围,其中嵌入了SARS-CoV-2的S蛋白、M蛋白和N蛋白。SARS-CoV-2侵入人呼吸道后,主要依靠病毒细胞表面S蛋白受体结合域识别宿主细胞受体血管紧张素转换酶2,然后与受体相互作用,使病毒进入宿主细胞。在SARS-CoV-2在人群中的流行和传播过程中,其基因经常出现突变。当SARS-CoV-2的不同亚变体或谱系同时感染人体时,这些病毒可能会重组,从而产生重组病毒株。某些突变或重组会影响病毒的生物学特性。例如,S蛋白上特定氨基酸的突变增强了SARS-CoV-2与血管紧张素转换酶2之间的亲和力,从而增强了病毒在细胞间复制和传播的能力。S蛋白上的一些氨基酸突变也会增加病毒对疫苗的免疫逃逸,减少不同亚变异体之间的交叉保护,导致突破性感染和一定比例的再感染。截至2022年底,世界卫生组织已指定了五个令人关注的变体,即Alpha (B.1.1.7)、Beta (B.1.351)、Gamma (P.1)、Delta (B.1.617.2)和Omicron (B.1.1.529)。与Delta等其他受关注的变异相比,2021年11月在人群中出现的Omicron变异的传播性和免疫逃逸能力显著增强,自2022年初以来,Omicron变异迅速取代Delta变异成为全球流行的主要变异。迄今为止,Omicron的5个亚变体(BA.1、BA.2、BA.3、BA.4和BA.5)已先后进化出709个序列谱系,其中包括72个重组谱系。随着SARS-CoV-2继续在全球传播,新的欧米克隆亚变体将不断出现。在全球流行了几个月的Omicron变异株为BA.5.2,但自2022年10月以来,具有更强免疫逃逸能力和传播力的BF.7、BQ.1、BQ.1.1等亚变异株和XBB等重组变异株迅速传播,取代BA.5.2成为部分国家和地区的优势流行毒株。国内外证据表明,Omicron变异菌株的肺致病性明显减弱,临床表现由肺炎转变为上呼吸道感染。国内常用的聚合酶链反应试验的诊断准确性未受影响,但部分上市单克隆抗体类药物的中和效果明显下降。SARS-CoV-2对紫外线、有机溶剂(如乙醚、75%乙醇、过氧乙酸和氯仿)以及含氯消毒剂敏感。含氯消毒剂和75%乙醇在临床实践和实验室中更常用,可以有效灭活病毒,但氯己定不能灭活病毒。2. 流行病学特征感染源sars - cov -2的患者是主要的感染源。感染在潜伏期可具有传染性,并在出现症状后3天内具有很强的传染性。2.2. 传播途径(一)病毒主要通过呼吸道飞沫和密切接触传播。㈡病毒可在相对封闭的环境中通过气溶胶传播。(三)接触被病毒污染的物体也可引起感染。2.3. 易受影响的群体人们通常是易受影响的。在感染或接种疫苗后可获得免疫力。 老年人群和有严重基础疾病的患者在感染后发生严重疾病和死亡的发生率高于一般人群,通过接种疫苗可以降低严重疾病发生和死亡的风险。3.3.1预防。接种SARS-CoV-2疫苗可降低SARS-CoV-2的感染率和发病率,是降低重症发病率和死亡率的有效手段。任何符合要求的人都应该接种疫苗。凡符合加强免疫条件的,应及时接种疫苗,增强免疫力。3.2. 一般注意事项保持良好的个人及环境卫生,饮食均衡,适当运动及休息,避免过度疲劳。提高卫生知识,养成良好的卫生习惯和生活方式,如保持“1米距离”,勤洗手,戴口罩,使用公共筷子,咳嗽或打喷嚏时捂住口鼻。保持室内通风,做好个人防护。4. 临床特点潜伏期一般为2-4天。主要表现为喉咙干、喉咙痛、咳嗽,常伴有中低烧。有些病人还会出现高烧,高烧的持续时间通常不超过3天。部分患者出现肌肉酸痛、嗅觉和味觉减退或丧失、鼻塞、流鼻涕、腹泻和结膜炎等症状。少数患者病情进展,伴有持续发热和肺炎相关表现。重症患者在5-7天后出现呼吸困难和/或低氧血症,并可迅速发展为急性呼吸窘迫综合征、感染性休克、难治性代谢性酸中毒、凝血功能障碍和多器官衰竭。罕见病例可表现为中枢神经系统受累。儿童感染后的临床表现与成人相似,尤其是高热较为常见。部分患儿可能有不典型症状,表现为呕吐、腹泻等胃肠道症状,或仅表现为低反应和呼吸急促。少数儿童可出现急性喉炎或喉气管炎,如声音嘶哑、哮喘或肺部喘息,但很少发生严重的呼吸窘迫。少数儿童可发生热性惊厥,并可发生危及生命的神经系统并发症,如脑炎、脑膜炎和脑病,甚至在极少数情况下可发生急性坏死性脑病、急性播散性脑脊髓炎和格林-巴罗综合征。受感染的儿童还可能出现多系统炎症综合征(misc),主要表现为发热伴皮疹、非化脓性结膜炎、粘膜炎症、低血压或休克、凝血功能障碍、急性胃肠道症状以及惊厥和脑水肿等脑病。一旦发生,这种疾病会在短时间内迅速恶化。大多数患者预后良好。老年人、慢性基础疾病患者、妊娠晚期和围产期妇女以及肥胖者的预后较差。4.2. 实验室检测4.2.1。在疾病早期,外周血白细胞计数正常或减少,淋巴细胞计数减少。部分患者肝酶、乳酸脱氢酶、肌肉酶、肌红蛋白、肌钙蛋白和铁蛋白水平升高。一些患者c反应蛋白(CRP)和红细胞沉降率升高,降钙素原水平正常。在重症和危重症患者中,d -二聚体增加,外周血淋巴细胞逐渐减少,炎症因子增加。4.2.2. (一)核酸检测:采用核酸扩增检测方法,可在呼吸道标本(鼻咽拭子、咽拭子、痰液等气管提取液)及其他标本中检测到SARS-CoV-2核酸。荧光定量聚合酶链反应是目前最常用的SARS-CoV-2检测方法。(二)抗原检测:采用胶体金法和免疫荧光法在呼吸道标本中检测SARS-CoV-2抗原。检测速度快,灵敏度与感染患者的病毒载量呈正相关。抗原检测阳性支持SARS-CoV-2诊断,但阴性不能排除。(三)病毒分离培养:SARS-CoV-2可通过呼吸道标本和粪便分离培养。(四)血清学检测:sars - cov -2特异性免疫球蛋白IgM、IgG抗体阳性。发病后1周内阳性率低。 儿童(i) RR升高;精神反应差,嗜睡和抽搐;(iii)外周血淋巴细胞减少和/或血小板减少;(iv)低(高)血糖水平和/或乳酸水平升高;炎症因子,如c反应蛋白、降钙素原和铁蛋白显著增加;天冬氨酸转氨酶、丙氨酸转氨酶和/或肌酸激酶显著增加;(vii) d -二聚体等凝血功能相关指标显著增加;(viii)颅脑显像显示脑水肿或其他变化,或胸部显像显示短时间内肺部病变发展迅速;患有基础疾病的儿童。9. (一)新冠肺炎的表
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引用次数: 1
Global Transmission of the penA Allele 60.001–Containing High-Level Ceftriaxone-Resistant Gonococcal FC428 Clone and Antimicrobial Therapy of Associated Cases: A Review 含高水平头孢曲松耐药淋球菌FC428克隆的penA等位基因60.001的全球传播及相关病例的抗菌治疗:综述
Q3 INFECTIOUS DISEASES Pub Date : 2023-01-23 DOI: 10.1097/IM9.0000000000000113
S. van der Veen
Abstract Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line therapy. However, ceftriaxone susceptibility has been waning in a number of countries over the last decade and ceftriaxone treatment failures have been reported, commonly as a result of sporadic high-level ceftriaxone-resistant strains. In recent years, N. gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or strains that acquired its main ceftriaxone resistance determinant, penA allele 60.001, have shown global transmission, resulting in ceftriaxone treatment failure in a number of cases. The FC428 clone was first encountered in Japan in 2015 and subsequently in China, Europe, Australia, North America and Southeast Asia afterward. Strains associated with the FC428 clone commonly display a ceftriaxone minimum inhibitory concentration of 0.5–1 mg/L. However, where penA alleles encountered in sporadic high-level ceftriaxone-resistant isolates induce an in vitro growth defect, penA allele 60.001 does not seem to affect in vitro growth. The limited impact of penA allele 60.001 on biological fitness might be associated with its successful global transmission. Although the FC428 clone displays high-level ceftriaxone resistance, most gonorrhea cases associated with this clone were still successfully cured with ceftriaxone when intramuscular or intravenous doses of 500 mg to 2 g were used. A successful alternative therapy seems to be ertapenem given at 1-g doses, although further clinical studies are required to validate ertapenem efficacy. This review summarizes the global transmission of strains associated with the FC428 clone and antimicrobial treatment of associated cases.
摘要淋病奈瑟菌是一种耐多药细菌病原体,头孢曲松是目前唯一推荐的一线治疗方法。然而,在过去十年中,许多国家对头孢曲松的易感性一直在下降,据报道,头孢曲松治疗失败,通常是由于散发的高水平头孢曲松耐药菌株。近年来,与高水平头孢曲松耐药性FC428克隆相关的淋病奈瑟菌菌株或获得其主要头孢曲松耐药决定簇penA等位基因60.001的菌株已显示出全球传播,导致许多病例中头孢曲松治疗失败。FC428克隆于2015年首次在日本发现,随后在中国、欧洲、澳大利亚、北美和东南亚发现。与FC428克隆相关的菌株通常显示头孢曲松的最低抑制浓度为0.5–1 mg/L。然而,当在散发的高水平头孢曲松耐药分离株中遇到的penA等位基因诱导体外生长缺陷时,penA等位点60.001似乎不影响体外生长。penA等位基因60.001对生物适应性的有限影响可能与其成功的全球传播有关。尽管FC428克隆显示出高水平的头孢曲松耐药性,但当肌肉注射或静脉注射剂量为500mg至2g时,与该克隆相关的大多数淋病病例仍然可以用头孢曲松成功治愈。虽然还需要进一步的临床研究来验证厄他培南的疗效,但一种成功的替代疗法似乎是以1g的剂量给予厄他培宁。这篇综述总结了与FC428克隆相关的菌株的全球传播和相关病例的抗菌治疗。
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引用次数: 2
The Top 100 Twitter Influencers in Infectious Diseases 推特传染病影响者前100名
Q3 INFECTIOUS DISEASES Pub Date : 2022-11-14 DOI: 10.1097/IM9.0000000000000111
Marcela Araujo de Oliveira Santana, S. Butt
Abstract Healthcare professionals in infectious diseases have been using Twitter to disseminate knowledge and interact with other professionals. This study aimed to identify and characterize the top 100 Twitter influencers in infectious diseases and to analyze the correlation between Twitter and academic influence. The Right Relevance Application Programming Interface was used to search for the term “infectious diseases,” producing a Twitter topic score for the top 100 infectious disease influencers. The influencers' Hirsch index (h-index) was compared with their Twitter topic score for a possible correlation. We identified that 46% of the infectious disease influencers were physicians. A correlation between the Twitter topic score of the infectious disease influencers and their h-index was not identified (r = 0.123, P = 0.22). The study also provides a list of the infectious disease influencers for those who have an interest in engaging and interacting with them on Twitter.
传染病领域的医疗保健专业人员一直在使用Twitter传播知识并与其他专业人员进行互动。本研究旨在识别和表征前100名Twitter传染病影响者,并分析Twitter与学术影响力之间的相关性。使用Right Relevance Application Programming Interface搜索“传染病”一词,生成100个传染病影响者的Twitter话题得分。影响者的赫希指数(h-index)与他们的推特话题得分进行了比较,以寻找可能的相关性。我们发现46%的传染病影响者是医生。传染病影响者的Twitter话题得分与其h指数之间没有相关性(r = 0.123, P = 0.22)。这项研究还为那些有兴趣在推特上与他们互动的人提供了一份传染病影响者名单。
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引用次数: 1
Minimum Core Genome Sequence Typing of Brucella From China 中国布鲁氏菌最小核心基因组序列分型
Q3 INFECTIOUS DISEASES Pub Date : 2022-11-04 DOI: 10.1097/IM9.0000000000000109
N. Zhao, B. Cui
Abstract The Gram-negative bacterial genus Brucella includes six classic species based on host specificity, pathogenicity and phenotypic differences. Four more Brucella species were identified in 2007. Although many Brucella genomes have been sequenced, genome sequences and analysis of Brucella strains isolated in China are still scarce. An efficient genome-based Brucella typing method is also needed. In this study, we used the minimum core genome (MCG) typing method to identify and type Brucella strains. Twenty Brucella isolates from China were newly sequenced. The genome sequences of 55 representative Brucella strains were downloaded. Among the 75 genomes, 1089 genes and 52,030 single nucleotide polymorphisms (SNPs) shared by all isolates were considered as the MCG genes and MCG SNPs. Using these 52,030 MCG SNPs, Brucella was divided into six MCG groups. In addition, average nucleotide identity (ANI) values and the distributions of 184 virulence genes were all computed. The proportions of virulence genes were 90.96%, 93.56%, 95.89%, 86.04%, 85.78% and 91.87% for MCG groups 1 to 6, respectively. The intragroup ANI values were higher than the intergroup values, further confirming the validity of the MCG taxonomy classification. Brucella melitensis and Brucella abortus, the two main Brucella species pathogenic to humans, were well separated from other species. With the development and cost reduction of next-generation sequencing, the MCG typing method can be used for rapid identification of Brucella, which can contribute to the rapid diagnosis of brucellosis and ensure timely and effective treatment.
根据宿主特异性、致病性和表型差异,革兰氏阴性细菌布鲁氏菌属包括6个经典种。2007年又发现了四种布鲁氏菌。虽然已经对许多布鲁氏菌基因组进行了测序,但中国分离的布鲁氏菌菌株的基因组序列和分析仍然很少。还需要一种高效的基于基因组的布鲁氏菌分型方法。本研究采用最小核心基因组(MCG)分型方法对布鲁氏菌菌株进行鉴定和分型。从中国分离的20株布鲁氏菌进行了新测序。下载55株代表性布鲁氏菌的基因组序列。在75个基因组中,共有1089个基因和52030个单核苷酸多态性(snp)被认为是MCG基因和MCG snp。利用这52,030个MCG snp,布鲁氏菌被分为6个MCG组。计算了184个毒力基因的平均核苷酸同一性(ANI)值和分布。MCG 1 ~ 6组毒力基因比例分别为90.96%、93.56%、95.89%、86.04%、85.78%和91.87%。组内ANI值高于组间ANI值,进一步证实了MCG分类分类的有效性。对人类致病的两种主要布鲁氏菌——melitensis布鲁氏菌和abortus布鲁氏菌与其他种类的布鲁氏菌分离较好。随着下一代测序技术的发展和成本的降低,MCG分型方法可用于布鲁氏菌的快速鉴定,有助于布鲁氏菌病的快速诊断和及时有效的治疗。
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引用次数: 0
A Systematic Review on Antituberculosis Drug Discovery and Antimycobacterial Potential of Biologically Synthesized Silver Nanoparticles: Overview and Future Perspectives 抗结核药物发现和生物合成银纳米粒子抗分枝杆菌潜力的系统综述:综述和未来展望
Q3 INFECTIOUS DISEASES Pub Date : 2022-11-01 DOI: 10.1097/IM9.0000000000000107
Christian K. Ezeh, C. Eze, U. Dibua, S. Emencheta
Abstract Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health problem. Green/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial agents. This review focused on the biological (green) synthesis of silver nanoparticles (AgNPs) as an alternative source of antimycobacterial agents. Data for this study were searched and screened from three electronic databases (Google Scholar, PubMed and ScienceDirect) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart. Data from in total 17 eligible studies were reported in this systematic review. Twelve of the 17 studies used plants to fabricate AgNPs, whereas the remaining five studies used microorganisms (bacteria and/or fungi). Silver as part of silver nitrate (AgNO3) was the metal precursor reported for the synthesis of AgNPs in these studies. Silver nanoparticles were mostly spherical, with sizes ranging from 12 to 140 nm. Results based on minimum inhibitory concentrations varied between studies and were divided into three groups: (i) those more effective than the antibiotic (controls), (ii) those more effective than plant extracts, and (iii) those less effective than the antibiotic controls. In addition, little or no cytotoxicity effects were reported. Silver nanoparticles were also shown to be highly specific or selective toward mycobacterial strains. This systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs, underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.
摘要耐药和侵袭性分枝杆菌菌株的快速出现和快速进化导致了目前的抗分枝杆菌药物危机,并使结核病成为一个主要的公共卫生问题。绿色/生物纳米技术是发现抗分枝杆菌制剂的一个有趣的研究领域。这篇综述的重点是生物(绿色)合成银纳米颗粒(AgNPs)作为抗分枝杆菌剂的替代来源。根据系统评价首选报告项目和荟萃分析流程图,从三个电子数据库(Google Scholar、PubMed和ScienceDirect)中搜索和筛选本研究的数据。本系统综述共报告了17项符合条件的研究的数据。17项研究中有12项使用植物制造AgNP,而其余5项研究使用微生物(细菌和/或真菌)。银作为硝酸银(AgNO3)的一部分是这些研究中报道的用于合成AgNPs的金属前体。银纳米颗粒大多是球形的,尺寸在12至140nm之间。基于最小抑制浓度的结果在不同的研究中各不相同,并分为三组:(i)比抗生素更有效的(对照组),(ii)比植物提取物更有效的,以及(iii)比抗生素对照组更无效的。此外,很少或没有细胞毒性作用的报道。银纳米颗粒也被证明对分枝杆菌菌株具有高度特异性或选择性。这篇系统综述强调了生物合成的AgNPs的抗分枝杆菌潜力,强调了使用毒性小、选择性高的生物合成方法发现/开发新的抗分枝菌剂的可能性。
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引用次数: 0
Cytokine Profiling in Influenza A Virus and Staphylococcal (Co-)Infections 甲型流感病毒和葡萄球菌(Co-)感染的细胞因子谱分析
Q3 INFECTIOUS DISEASES Pub Date : 2022-11-01 DOI: 10.1097/IM9.0000000000000108
Lea A. Tölken, Antje D. Paulikat, Fabian Cuypers, Sebastian B. Skorka, S. Hammerschmidt, N. Siemens
Abstract Influenza A virus and Staphylococcus aureus are common causative agents of pneumonia. Co-infections with these two pathogens frequently occur and are characterized, among others, by higher morbidity and mortality due to hyper-inflammation of the lungs. Here, we aimed to profile systemic and local cytokine composition at early acute stages of pneumonia in a murine model. All mice recovered from single influenza A virus and/or staphylococcal infections. In contrast, co-infections led to a severe clinical outcome. While distinct cytokine patterns were detected in lungs of single-pathogen-infected animals, co-infections combined both virus- and bacteria-driven responses. However, analyses of infected human primary monocytic cells as well as bronchial epithelial cells did not reflect murine profiles. Based on infectious dose, mainly bacteria-driven responses were noted. The impact of single cells to cytokine composition of the lungs and translation of murine studies to humans remains uncertain and warrants further studies.
甲型流感病毒和金黄色葡萄球菌是常见的肺炎病原体。这两种病原体的合并感染经常发生,其特点之一是由于肺部的高度炎症导致较高的发病率和死亡率。在这里,我们的目的是在小鼠模型中分析肺炎早期急性阶段的全身和局部细胞因子组成。所有小鼠均从单一甲型流感病毒和/或葡萄球菌感染中恢复。相反,合并感染导致严重的临床结果。虽然在单一病原体感染动物的肺部检测到不同的细胞因子模式,但合并感染结合了病毒和细菌驱动的反应。然而,对感染的人原代单核细胞和支气管上皮细胞的分析并没有反映小鼠的特征。根据感染剂量,主要注意到细菌驱动的反应。单细胞对肺部细胞因子组成的影响以及小鼠研究对人类的转化仍然不确定,需要进一步研究。
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引用次数: 1
Identification of Persister Drug Combination Clinafloxacin + Cefuroxime + Gentamicin That Eradicates Persistent Pseudomonas aeruginosa Infection in a Murine Cystic Fibrosis Model 克林沙星+头孢呋辛+庆大霉素联合用药根除小鼠囊性纤维化模型中铜绿假单胞菌持续性感染的鉴定
Q3 INFECTIOUS DISEASES Pub Date : 2022-10-27 DOI: 10.1097/IM9.0000000000000106
Yuting Yuan, R. Yee, N. Gour, Xinzhong Dong, Jie Feng, W. Shi, Y. Zhang
Abstract Pseudomonas aeruginosa can cause persistent infections, such as biofilm infections, in cystic fibrosis patients, which are difficult to cure due to non-growing persister bacteria that are not effectively killed by the current treatments. While antibiotic activity against growing P. aeruginosa is well documented, their activity against non-growing stationary phase cultures is less clear. Here, we evaluated six major classes of antibiotics, including cell wall and cell membrane inhibitors, protein synthesis inhibitors, DNA synthesis inhibitors, RNA synthesis inhibitors, sulfa drugs and nitrofurantoin, for their activity against growing and non-growing P. aeruginosa. We found that cell wall and cell membrane inhibitors (cefuroxime and colistin), DNA synthesis inhibitors (clinafloxacin) and sulfa drugs (sulfamethoxazole) had good activity against stationary-phase bacteria, while protein synthesis inhibitors (gentamicin), RNA synthesis inhibitor (rifampin) and nitrofurantoin showed relatively poor activity. Clinafloxacin was the only drug able to completely eradicate stationary-phase bacteria within four days. The cefuroxime + gentamicin + clinafloxacin combination was able to kill all bacteria from a biofilm within two days, whereas the clinically used drug combination cefuroxime + gentamicin/colistin only partially killed the biofilm bacteria. In a murine persistent cystic fibrosis lung infection model, only the cefuroxime + gentamicin + clinafloxacin drug combination eradicated all bacteria from the lungs, whereas clinafloxacin alone, cefuroxime + clinafloxacin or the currently recommended drug combination cefuroxime + gentamicin failed to do so. The complete eradication is a property of the clinafloxacin combination, as the otherwise identical levofloxacin combination did not clear the bacterial loads from the lungs. Our findings offer new therapeutic options for more effective treatment of persistent P. aeruginosa infections, with possible implications for treating other persistent infections.
摘要铜绿假单胞菌可导致囊性纤维化患者的持续感染,如生物膜感染,由于目前的治疗方法无法有效杀死不生长的持续细菌,这种感染很难治愈。虽然抗生素对生长中的铜绿假单胞菌的活性已被充分证明,但它们对非生长固定相培养物的活性尚不清楚。在这里,我们评估了六类主要的抗生素,包括细胞壁和细胞膜抑制剂、蛋白质合成抑制剂、DNA合成抑制剂、RNA合成抑制剂、磺胺类药物和呋喃妥因,它们对生长和非生长的铜绿假单胞菌的活性。我们发现细胞壁和细胞膜抑制剂(头孢呋辛和粘菌素)、DNA合成抑制剂(克林霉素)和磺胺类药物(磺胺甲恶唑)对固定相细菌具有良好的活性,而蛋白质合成抑制剂(庆大霉素)、RNA合成抑制剂(利福平)和呋喃妥因的活性相对较差。Clinafloxacin是唯一一种能够在四天内完全根除固定相细菌的药物。头孢呋辛+庆大霉素+克林霉素组合能够在两天内杀死生物膜中的所有细菌,而临床使用的药物组合头孢呋辛+庆大霉素/粘菌素仅部分杀死生物膜细菌。在小鼠持续性囊性纤维化肺部感染模型中,只有头孢呋辛+庆大霉素+克林沙星药物组合根除了肺部的所有细菌,而单独的克林沙星、头孢呋辛和克林沙星或目前推荐的药物组合头孢呋辛加庆大霉素未能做到这一点。完全根除是克林沙星组合的一个特性,因为在其他方面相同的左氧氟沙星组合不能清除肺部的细菌载量。我们的发现为更有效地治疗持续性铜绿假单胞菌感染提供了新的治疗选择,并可能对治疗其他持续性感染产生影响。
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引用次数: 1
Vibrio Septicemia Diagnosed With Next-Generation Sequencing: A Case Report 用新一代测序诊断败血症弧菌:一例报告
Q3 INFECTIOUS DISEASES Pub Date : 2022-10-02 DOI: 10.1097/IM9.0000000000000104
Zutao Chen, Xiao Liu, Yajuan Wang, Yun-hai Yao
Abstract Vibrio vulnificus and Vibrio parahaemolyticus are marine gram-negative bacilli that can cause septicemia and gastrointestinal and wound infections. Early suspicion, diagnosis and appropriate antibiotic therapy for those infections are essential as delay can adversely affect the outcome. Here, we report a patient who developed a V. vulnificus and V. parahaemolyticus infection after contact with a fishing net. The cause of infection was finally diagnosed by metagenomic next-generation sequencing. The patient required an emergency amputation of the upper- and middle-third of the right upper limb.
摘要创伤弧菌和副溶血性弧菌是海洋革兰氏阴性杆菌,可引起败血症、胃肠道和伤口感染。对这些感染进行早期怀疑、诊断和适当的抗生素治疗至关重要,因为延迟可能会对结果产生不利影响。在这里,我们报告了一名患者,他在接触渔网后感染了创伤弧菌和副溶血弧菌。感染原因最终通过宏基因组下一代测序得到诊断。患者需要紧急截肢右上肢的中三分之一和上三分之一。
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引用次数: 0
The Utility of Voided Urine Samples as a Proxy for the Vaginal Microbiome and for the Prediction of Bacterial Vaginosis 排尿样本作为阴道微生物组和细菌性阴道病预测指标的应用
Q3 INFECTIOUS DISEASES Pub Date : 2022-09-27 DOI: 10.1097/IM9.0000000000000103
Bin Zhu, Christopher Diachok, Laahirie Edupuganti, David J. Edwards, Jeffrey R. Donowitz, K. Tossas, A. Matveyev, Katherine M. Spaine, Vladimir Lee, M. Serrano, Gregory A. Buck
Abstract Recent work has shown that the vaginal microbiome exerts a strong impact on women's gynecological health. However, collection of vaginal specimens is invasive and requires previous clinical training or the involvement of a trained clinician. In contrast, urine sample collection is routine and noninvasive and does not require involvement of a clinician. We sought to compare the vaginal and urogenital microbiomes to assess the utility of voided urine samples as a proxy for the vaginal microbiome. Paired urogenital and vaginal samples were collected from pregnant women and characterized by 16S rRNA taxonomic profiling. We examined diversities and compositions of paired urogenital and vaginal microbiomes using five discrete strategies to explore the similarity between the vaginal and urogenital microbiomes. A strategy comparing the paired urogenital and vaginal microbiomes in which taxa were assigned using the STIRRUPS database and urine-specific taxa were removed showed no significant difference in diversity and composition between the paired urogenital and vaginal microbiomes. Moreover, the relative abundances of common vaginal taxa were linearly correlated with those in the paired urogenital microbiomes. These similarities suggest that voided urine samples could represent a noninvasive protocol for accurate profiling of the vaginal microbiome with likely clinical applications. Finally, a machine learning model was established in which the voided urine microbiome was compared favorably to the vaginal microbiome in predicting bacterial vaginosis.
摘要最近的研究表明,阴道微生物组对女性的妇科健康有很大影响。然而,阴道标本的采集是侵入性的,需要之前的临床培训或训练有素的临床医生的参与。相反,尿液样本采集是常规的和非侵入性的,不需要临床医生的参与。我们试图比较阴道和泌尿生殖道微生物组,以评估排泄尿液样本作为阴道微生物组替代品的效用。从孕妇身上采集成对的泌尿生殖道和阴道样本,并通过16S rRNA分类图谱进行表征。我们使用五种离散策略检测了配对的泌尿生殖道和阴道微生物组的多样性和组成,以探索阴道和泌尿生殖道微生物组之间的相似性。一项比较配对的泌尿生殖道和阴道微生物群的策略显示,配对的泌尿生殖器和阴道微生物组之间的多样性和组成没有显著差异,其中使用STIRRUPS数据库分配了分类群,并删除了尿液特异性分类群。此外,常见阴道分类群的相对丰度与配对的泌尿生殖微生物群中的相对丰度呈线性相关。这些相似之处表明,排泄的尿液样本可能是一种无创的方案,可以准确分析阴道微生物组,并可能在临床上应用。最后,建立了一个机器学习模型,在该模型中,在预测细菌性阴道病时,将排泄尿液微生物组与阴道微生物组进行了有利的比较。
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引用次数: 0
Global Transmission of Human Immunodeficiency Virus 1 Subtype C and Its Impact on the Circulation of B/C Recombination Strains in China 人免疫缺陷病毒1型C亚型的全球传播及其对中国B/C重组毒株传播的影响
Q3 INFECTIOUS DISEASES Pub Date : 2022-09-15 DOI: 10.1097/IM9.0000000000000102
Zhanmou Liu, Yanling Liang, Yi Feng, Kang Li, Y. Shao
Abstract This study aimed to reconstruct the origin and worldwide epidemic history of human immunodeficiency virus (HIV) 1 subtype C and comprehend how HIV-1 subtype C was introduced into and spread throughout China in the form of B/C recombinant strains. Envelope sequences of HIV-1 subtype C and some other subtypes deposited before December 31, 2020 were downloaded from the Los Alamos HIV Database and the Chinese National Center for AIDS/STD Control and Prevention Database. The available sequences were screened for quality, and Bayesian analysis was used to build the maximum clade credibility evolutionary tree to analyze and judge the origin and spread of HIV-1 subtype C. HIV-1 subtype C originated in central Africa around 1952, then spread to southern Africa around 1969 and to eastern Africa around 1973. HIV-1 subtype C from southern Africa was introduced into India in 1977. HIV-1 subtype C of eastern Africa was introduced into Brazil in 1987. Indian HIV-1 subtype C was exported to China in three migration events during the period from 1986 to 1989. The two predominant recombinants in China (CRF07_BC and CRF08_BC) emerged in 1988 and 1990, respectively. Other B/C recombinants, namely, CRF64_BC, CRF61_BC and CRF62_BC, originated in 1993, 2002 and 2000, respectively. Our study has reconstructed the global origin and evolutionary history of HIV-1 subtype C. In addition, our study demonstrated that the Chinese HIV-1 subtype C originated from three related Indian lineages around the mid to late 1980s and, since then, has formed some B/C recombinants with subtype B that caused a widespread epidemic in China.
摘要本研究旨在重建人类免疫缺陷病毒(HIV)1亚型C的起源和全球流行史,了解HIV-1亚型C是如何以B/C重组株的形式传入中国并在中国各地传播的。2020年12月31日前保存的HIV-1 C亚型和其他一些亚型的包膜序列从洛斯阿拉莫斯HIV数据库和中国国家艾滋病/性病预防控制中心数据库下载。对可用序列进行质量筛选,并使用贝叶斯分析建立最大分支可信度进化树,以分析和判断HIV-1 C亚型的起源和传播。HIV-1 C亚型于1952年左右起源于中非,1969年左右传播至南部非洲,1973年左右传播到东部非洲。1977年,来自南部非洲的HIV-1亚型C被引入印度。非洲东部的HIV-1亚型C于1987年被引入巴西。1986年至1989年期间,印度HIV-1 C亚型在三次迁徙事件中出口到中国。中国两个主要的重组子(CRF07_BC和CRF08_BC)分别出现在1988年和1990年。其他B/C重组体,即CRF64_BC、CRF61_BC和CRF62_BC,分别起源于1993年、2002年和2000年。我们的研究重建了HIV-1 C亚型的全球起源和进化史。此外,我们的研究表明,中国HIV-1 C亚型起源于20世纪80年代中后期左右的三个相关的印度谱系,从那时起,与B亚型形成了一些B/C重组体,并在中国引起了广泛的流行。
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引用次数: 0
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Infectious microbes & diseases
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