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Clinical Pharmacology of the Single Tablet Regimen Bictegravir/Emtricitabine/Tenofovir Alafenamide in the evolving era of antiretroviral therapies. 在抗逆转录病毒疗法不断发展的时代,单片疗法 Bictegravir/Emtricitabine/Tenofovir Alafenamide 的临床药理学。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Giovanni Di Perri, Stefano Bonora

In this fast-evolving era of antiretroviral chemotherapy, the single-tablet regimen (STR) BIC/FTC/TAF, an oral regimen including a potent INSTI (strand-transfer integrase inhibitors) like Bictegravir plus two different NRTIs (Nucleoside Reverse Transcriptase Inhibitors), is increasingly challenged by new oral combinations. Furthermore, long-acting injectable drugs have also been developed and others are being under development. Notably, no new STR consisting of two NRTIs plus a 3rd drug like an INSTI are in the industrial pipeline. However, many People with HIV (PWH) still need potent multidrug regimens, especially those newly diagnosed with advanced HIV (defined late presenters), which represent over 50% of new infections. The asymmetrical comparison between a potent STR like BIC/FTC/TAF and new combinations is difficult to make. By comparing the STR BIC/FTC/TAF, the most representative of potent multi-drug regimens, with all approved new options, we can distinguish some features that are worthy of attention. The stronger genetic barrier and the better forgiveness resulting from BIC/FTC/TAF is self-evident, with the extra coverage here provided by the remarkable pharmacologic properties of TAF, consisting of great diffusion into target cells, long persistence at high concentration, and a much lower plasma exposure. On the pharmacokinetic side, the main difference is between oral and long-acting injectable regimens. Pk of long-acting injectables consists of a single peak (followed by a slow decrease in drug concentration), while with oral regimens daily C max - C trough fluctuations take place instead. The latter property of oral regimens should be taken into account whenever the Pk exposure is suboptimal, as it might allow inhibition of the growth of quasi-species that are less sensitive. The choice of the new combinations including long acting injectables instead of the STR BIC/FTC/TAF might be made for sure for several reasons, but compared to the past when combinations included TDF, toxicity by TAF is no longer an issue today. The size of the tablet and its net weight may be disproportional to the number of drugs, as there are multidrug regimens like the STR BIC/FTC/TAF whose weight may be lower than those of the new oral combinations INSTI-based for both naive and switching PWH. Although multi-drug regimens like the STR BIC/FTC/TAF are no longer in development, their use in clinical practice will still remain substantial for a long time and knowledge of their properties is necessary to properly select the most appropriate regimens for PWH.

在这个抗逆转录病毒化疗快速发展的时代,单片疗法(STR)BIC/FTC/TAF(一种口服疗法,包括一种强效 INSTI(链转移整合酶抑制剂),如 Bictegravir 加上两种不同的 NRTI(核苷类逆转录酶抑制剂))正日益受到新型口服组合疗法的挑战。此外,长效注射药物也已开发出来,其他药物也在开发之中。值得注意的是,目前还没有由两种 NRTI 加上第三种药物(如 INSTI)组成的新的 STR 进入工业化流水线。然而,许多艾滋病病毒感染者(PWH)仍然需要强效的多药治疗方案,特别是那些新诊断出的晚期艾滋病病毒感染者(定义为晚期患者),他们占新感染者的 50%以上。像 BIC/FTC/TAF 这样的强效 STR 与新的组合药物之间的不对称比较很难进行。通过将 BIC/FTC/TAF 这种最能代表强效多药方案的 STR 与所有已批准的新方案进行比较,我们可以发现一些值得关注的特点。BIC/FTC/TAF具有更强的基因屏障和更好的耐受性,这一点是不言而喻的,TAF显著的药理特性提供了额外的覆盖面,包括向靶细胞的巨大扩散、在高浓度下的长期持久性和更低的血浆暴露。在药代动力学方面,口服和长效注射方案之间存在主要差异。长效注射剂的 Pk 只有一个峰值(随后药物浓度缓慢下降),而口服药物的 C 最大值-C 谷值每天都有波动。只要 Pk 暴露不理想,就应考虑口服药物的后一种特性,因为它可能会抑制敏感性较低的准物种的生长。选择包括长效注射剂而不是 STR BIC/FTC/TAF 的新组合可能有几个原因,但与过去包括 TDF 的组合相比,TAF 的毒性如今已不再是一个问题。片剂的大小和净重可能与药物的数量不成比例,因为对于新感染者和转换感染的 PWH 而言,STR BIC/FTC/TAF 等多药方案的重量可能低于基于 INSTI 的新型口服组合。虽然 STR BIC/FTC/TAF 等多药方案已不再开发,但在临床实践中仍将长期大量使用,因此有必要了解这些方案的特性,以便为 PWH 正确选择最合适的方案。
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引用次数: 0
One stage extraction and reimplantation of ICD/PM in patients with CIED related endocarditis and spondiloscitis due to E. faecalis treated with double beta-lactam combination: ampicillin plus ceftobiprole. 使用双β-内酰胺类复方制剂:氨苄西林加头孢比普洛治疗因粪大肠杆菌引起的与 CIED 相关的心内膜炎和脊柱炎患者的一期摘除和再植入 ICD/PM。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Maria Lucia Narducci, Davide Pecori, Massimo Imazio, Luca Rebellato, Monica Geminiani, Giulia Bontempo, Luca Martini, Simone Giuliano, Carlo Tascini

The time of re-implantation of removed CIED for local infection or endocarditis has been debated because no randomized studies are available. Many authors prefer to delay reimplantation to the time of blood culture negative or clinical stability. In this case report we describe the case of E. faecalis CIED endocarditis treated with the combination ampicillin plus ceftobiprole and one-stage removal and re-implantation with early follow-up without relapse of infection. In case of E. faecalis infection, we hypothesize that ampicillin plus ceftobiprole combination might have bactericidal and anti-biofilm activity, therefore allowing one state re-implantation without relapse.

由于没有随机研究,对于因局部感染或心内膜炎而摘除的 CIED 的再植入时间一直存在争议。许多学者倾向于将再次植入时间推迟到血培养阴性或临床病情稳定时。在本病例报告中,我们描述了一例粪肠球菌CIED心内膜炎病例,该病例采用氨苄西林加头孢比普联合疗法,并进行了一期摘除和再次植入,早期随访,感染未复发。对于粪肠球菌感染,我们推测氨苄西林加头孢比普联合疗法可能具有杀菌和抗生物膜活性,因此可以在一个阶段内重新植入而不会复发。
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引用次数: 0
Comparison between rapid and laboratory serological tests in the context of the first responders during the SARS-CoV-2 outbreak: are the two tests interchangeable? 在 SARS-CoV-2 爆发期间,对第一反应人员进行快速血清学检测和实验室血清学检测的比较:这两种检测是否可以互换?
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Simone Murganti, Edoardo Cavalieri d'Oro, Matteo Villa, Antonio Papagni, Andrea Malizia

The SARS-CoV-2 virus appeared and was discovered in the year 2019, marking its significance. The spread of the virus also had serious consequences for national safety; members of the Police and Fire Brigade contracted the infection and therefore the efficiency of their operational activity decreased. Since the beginning of 2020, the biological laboratory of the Chemical Biological Radiological Nuclear (CBRN) unit of Milan's Fire Brigade headquarters performed thousands of serological tests to monitor the health of the Fire Brigade and various branches of the Police Forces. The aim of this study is to evaluate the degree of concordance and interchangeability between a lateral flow immunochromatographic assay (LFIA) and an automated laboratory immunoassay with different viral targets by comparing the data gathered from a sample group of firemen and policemen participating in a serological screening campaign. The serological tests used in this study are the LYHER® Novel Coronavirus (2019-nCoV) IgM/IgG Antibody Combo Test Kit and the Elecsys® Anti-SARS-CoV-2. The degree of concordance was computed using Cohen's kappa, with a result of 0.78 (CI 95%, 0.661-0.898), which is equivalent to a substantial agreement measured between the two tests. Additionally, the sensitivity of both serological tests was found to be 97%.

SARS-CoV-2 病毒在 2019 年出现并被发现,这标志着它的重要性。病毒的传播也对国家安全造成了严重后果;警察和消防队成员感染了病毒,因此他们的业务活动效率下降。自 2020 年初以来,米兰消防队总部化学、生物、放射、核(CBRN)部门的生物实验室进行了数千次血清学检测,以监测消防队和警察部队各部门的健康状况。本研究的目的是通过比较从参加血清学筛查活动的消防员和警察样本组收集到的数据,评估采用不同病毒目标的侧流免疫层析(LFIA)和自动实验室免疫测定之间的一致性和互换性。本研究中使用的血清学检测方法是 LYHER® 新型冠状病毒(2019-nCoV)IgM/IgG 抗体组合检测试剂盒和 Elecsys® 抗 SARS-CoV-2 检测试剂盒。使用科恩卡帕(Cohen's kappa)计算的吻合度为 0.78(CI 95%,0.661-0.898),这相当于测得两种检测方法的吻合度非常高。此外,两种血清检验的灵敏度均为 97%。
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引用次数: 0
Rifampin-like Red-brown Bronchial Secretions Staining in a Patient Treated with Cefiderocol. 一名接受头孢羟氨苄治疗的患者出现利福平样红棕色支气管分泌物染色。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Tommaso Lupia, Marco Casarotto, Antonio D'Avolio, Jacopo Mula, Antonio Curtoni, Silvia Corcione, Francesco Giuseppe De Rosa

Numerous drugs are known to alter the colour of human body fluids. Although drug-induced bronchial secretions staining is normally harmless, it may frighten the patient and could lead to unnecessary clinical inquiries. Cefiderocol is often removed renally as an unmodified drug; bronchial secretion staining has not been seen at doses used in clinical practice. We report a possible first case of bronchoalveolar lavage staining occurred during Cefiderocol treatment in a critical patient.

众所周知,许多药物会改变人体体液的颜色。虽然药物引起的支气管分泌物染色通常是无害的,但它可能会吓到病人,并可能导致不必要的临床检查。头孢羟氨苄通常作为一种未经改良的药物从肾脏排出;在临床实践中使用的剂量尚未出现支气管分泌物染色的情况。我们报告了可能是首例在治疗危重病人的头孢羟氨苄期间出现支气管肺泡灌洗液染色的病例。
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引用次数: 0
Epidemiological characteristics and related risk factors of mixed infection in children with mycoplasma pneumoniae pneumonia. 肺炎支原体肺炎患儿混合感染的流行病学特征和相关风险因素。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Wenli Lv, Chunyan Guo, Guofeng Lv, Xueqin Xi

Mycoplasma pneumoniae infection is a manifestation of pneumonia, which can be combined with multiple bacterial flora infection at the same time. This study explored the epidemiological characteristics and related risk factors of mixed infection in children with mycoplasma pneumonia (MP). 462 children with MP were enrolled and divided into simple infection and mixed infection groups. The mixed infection group was further divided into concurrent bacteria, virus, and chlamydia groups. Clinical data were collected to explore the epidemiological characteristics, and the related factors were analyzed by logistic regression. The co-infection rate was the highest in the mixed infection group (50.27%). Children under 1 year of age had the highest bacterial co-infection rate (40.95%). Children aged 1-5 years and >5 years had the highest viral co-infection rate (39.53%, 51.51%). Patients were more likely to be infected with virus from September to November (52.73%), and patients were more likely to be infected with bacteria from December to February (52.73%). The independent risk factors for concurrent viral, bacterial, and chlamydia infections were extrapulmonary complications, fever >10 days, high white blood cell count (WBC), and age, respectively. Conclusion: analysis of the epidemiological characteristics and risk factors of mixed infection in children with MP can provide guidance for clinicians to formulate a more reasonable diagnosis and treatment plan, reduce the occurrence of mixed infection, and improve the treatment effect.

肺炎支原体感染是肺炎的一种表现形式,可同时合并多种细菌菌群感染。本研究探讨了支原体肺炎(MP)患儿混合感染的流行病学特征和相关风险因素。研究共招募了 462 名支原体肺炎患儿,将其分为单纯感染组和混合感染组。混合感染组又分为细菌组、病毒组和衣原体组。收集临床数据以探讨流行病学特征,并通过逻辑回归分析相关因素。混合感染组的合并感染率最高(50.27%)。1 岁以下儿童的细菌合并感染率最高(40.95%)。1-5 岁和 5 岁以上儿童的病毒合并感染率最高(39.53%、51.51%)。9 月至 11 月的患者更容易感染病毒(52.73%),12 月至 2 月的患者更容易感染细菌(52.73%)。并发病毒、细菌和衣原体感染的独立危险因素分别是肺外并发症、发烧超过 10 天、白细胞计数(WBC)高和年龄。结论:分析MP患儿混合感染的流行病学特征和危险因素,可指导临床医生制定更合理的诊疗方案,减少混合感染的发生,提高治疗效果。
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引用次数: 0
PRESTIGIO RING: "A 28-year-old highly treatmentexperienced man with vertical HIV infection on ibalizumab therapy: ART simplification perspectives". prestigio ring:"一名接受伊巴珠单抗治疗的 28 岁高度治疗经验男性艾滋病垂直感染者:简化抗逆转录病毒疗法的视角"。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Rebecka Papaioannu Borjesson, Maurizio Zazzi, Francesco Saladini, Maria Mercedes Santoro, Daniele Armenia, Vincenzo Spagnuolo, Antonella Castagna

Due to a limited range of effective treatment options, highly treatment-experienced (HTE) people with HIV (PWH) still struggle to maintain virological suppression and obtain an adequate immunological recovery. To increase the likelihood of virologic success, HTE PWH require an individualized treatment regimen based on cumulative genotypic resistance testing (GRT) data, potential drug-drug interactions, and adherence. From the PRESTIGIO Registry, we present a case of a 28-year-old man with vertically transmitted HIV-1 infection, on therapy with an ibalizumab-including regimen and desiring a treatment simplification. In January 2024, the patient was started on a lenacapavir-containing regimen along with optimized background therapy in an attempt to maintain sustained virological suppression, simplify antiretroviral regimen, and potentially increase CD4+ T-cell count. At six months follow-up evaluation, virological suppression was confirmed, and an increase in CD4+ T-cell count of 60 cells/μL was observed. Close follow-up of this patient is ongoing.

由于有效治疗方案的范围有限,有高度治疗经验(HTE)的艾滋病病毒感染者(PWH)仍在努力维持病毒学抑制并获得充分的免疫学恢复。为了提高病毒学治疗成功的可能性,HTE 患者需要根据累积的基因型耐药性检测(GRT)数据、潜在的药物相互作用和依从性来制定个性化的治疗方案。我们从 PRESTIGIO 登记处获得了一例 28 岁男性垂直传播 HIV-1 感染者的病例,该患者正在接受包括伊巴珠单抗在内的治疗方案,并希望简化治疗。2024 年 1 月,患者开始接受含来那帕韦的治疗方案和优化的背景治疗,试图维持持续的病毒抑制、简化抗逆转录病毒治疗方案并增加 CD4+ T 细胞数量。在 6 个月的随访评估中,病毒抑制得到了证实,CD4+ T 细胞计数增加了 60 个细胞/μL。目前正在对该患者进行密切随访。
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引用次数: 0
Safety and Pharmacokinetic Profiles of Subcutaneous Administration of Beta-Lactams: A Systematic Review. β-内酰胺类药物皮下注射的安全性和药代动力学特征:系统回顾
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Chiara Moreal, Stefania Chiappinotto, George G Zhanel, Simone Lanini, Luca Montanari, Alvisa Palese, Carlo Tascini

Beta-lactams are extensively used antibiotics known for their safety and effectiveness. The rise in patients who receive care in outpatient settings has increased the interest in subcutaneous administration (SA). The aim of the study is to assess the safety and pharmacokinetic (PK) profiles of SA of beta-lactams compared with other routes. The protocol was registered in the PROSPERO database and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. Online databases were searched, and the quality of the eligible studies was assessed. The data extracted related to adverse events (AEs) and PK were summarised narratively. Sixteen studies were included. The reported AEs were generally mild, localised, and temporary. Although SA and intravenous administration had similar PK profiles, SA resulted in lower peak drug concentrations and slower absorption. Heterogeneity in the populations, medication delivery, outcome measures, and methodological quality emerged across the studies. The mild severity of AEs suggests that SA is a viable route. Additionally, SA appears to demonstrate effective PK profiles and delays drug release, with potential to reduce the dosing frequency and prolong the therapeutic effects. SA of beta-lactams is a promising viable alternative to intravenous administration, potentially enhancing treatment in the outpatient and long-term care settings.

β-内酰胺类抗生素因其安全性和有效性而被广泛使用。随着在门诊接受治疗的患者人数增加,人们对皮下注射(SA)的兴趣也随之增加。本研究旨在评估与其他途径相比,β-内酰胺类药物皮下注射的安全性和药代动力学(PK)特征。研究方案已在 PROSPERO 数据库中注册,并遵循了《系统综述和元分析首选报告项目》指南。对在线数据库进行了检索,并对符合条件的研究进行了质量评估。对提取的不良事件(AEs)和PK相关数据进行了叙述性总结。共纳入 16 项研究。所报告的不良反应一般较轻微、局部且暂时。虽然 SA 和静脉给药具有相似的 PK 曲线,但 SA 导致峰值药物浓度较低且吸收较慢。各项研究在研究对象、给药方式、结果测量和方法质量等方面都存在异质性。不良反应的严重程度较轻,这表明 SA 是一种可行的途径。此外,SA 似乎显示出有效的 PK 曲线,并能延迟药物释放,有可能减少用药频率并延长疗效。β-内酰胺类药物的 SA 是一种替代静脉给药的可行方法,具有广阔的前景,有可能提高门诊和长期护理环境中的治疗效果。
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引用次数: 0
The Symbiotic Defence: Lung Microbiota and The Local Immune System. 共生防御:肺部微生物群与局部免疫系统。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Ozel Yuruker, İskender Yılmaz, Meryem Güvenir

Microbiota defines all microorganisms that are vital for our immunological, hormonal, and metabolic homeostasis by living symbiotically in different parts of our body. On the other hand, the microbiome is a collection of microorganisms that can be detected together. The lungs are constantly exposed to airborne microorganisms found in the upper respiratory tract. Until recently, the lower respiratory tract was considered sterile, as bacteria were rarely isolated from the lungs by conventional culture methods. Most chronic inflammatory lung diseases are caused by dysregulation of the lung microbiota, which has been discussed in many review papers. However, little is known whether microbiota dysymbiosis is a consequence or a cause of these diseases. In this review, we provide an overview of lung microbiota and lung immunity.

微生物群是指在我们身体不同部位共生的、对我们的免疫、荷尔蒙和新陈代谢平衡至关重要的所有微生物。另一方面,微生物组是可以一起检测到的微生物的集合。肺部经常暴露于上呼吸道中的微生物。直到最近,下呼吸道还被认为是无菌的,因为用传统的培养方法很少能从肺部分离出细菌。大多数慢性肺部炎症性疾病都是由肺部微生物群失调引起的,许多综述论文都对此进行了讨论。然而,微生物群共生失调究竟是这些疾病的结果还是原因,人们对此知之甚少。在这篇综述中,我们将概述肺微生物群和肺免疫。
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引用次数: 0
Analysis of infection indicators and risk factors for influenza A after the COVID-19 pandemic. COVID-19 大流行后甲型流感的感染指标和风险因素分析。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Rui Ying Wang, Yu Wang, Xin Xin Wang, Bin Yan Wu, Hong Pei Wu, Hui Zheng Hu

The flu outbreak after the coronavirus disease 2019 (COVID-19) pandemic has put a heavy burden on the medical system. We aimed to investigate the infection indicators and risk factors for influenza A virus, with the intention of offering valuable insights for clinical diagnosis and treatment. A total of 1590 throat swabs were collected from patients with influenza-like illness admitted to our hospital for treatment in March 2023. Influenza virus in infected patients was detected by the rapid antigen method and qPCR. We used statistical methods to compare clinical manifestations and laboratory tests between positive and negative patients. Among the 1590 influenza-like illness patients, 1004 (63.1%) were infected with influenza A, mainly children aged 0-9 years (52.8%); more males than females were infected, and the main clinical symptoms were fever, cough, diarrhea, nausea and vomiting, and muscle soreness. The leukocyte (WBC), lymphocyte (LYM), eosinophil (EOS), platelet (PLT), C-reactive protein (CRP) and lymphocyte/monocyte (LMR) levels in the positive group were lower than those in the negative group, while the neutrophil (NEU) and monocyte (MON) levels were higher than those in the negative group (P<0.05). Multivariate logistic regression analysis showed that age 0-9 years, cough, antiviral treatment time>48 h, and reduced PLT and LMR levels were independent risk factors for influenza A patients.

2019 年冠状病毒病(COVID-19)大流行后爆发的流感给医疗系统带来了沉重的负担。我们旨在研究甲型流感病毒的感染指标和风险因素,以期为临床诊断和治疗提供有价值的见解。2023 年 3 月,我们从本院收治的流感样疾病患者中采集了 1590 份咽拭子。通过快速抗原法和 qPCR 法检测感染者体内的流感病毒。我们采用统计学方法比较了阳性和阴性患者的临床表现和实验室检测结果。在 1590 名流感样病患者中,1004 人(63.1%)感染了甲型流感病毒,主要是 0-9 岁的儿童(52.8%);感染者中男性多于女性,主要临床症状为发热、咳嗽、腹泻、恶心呕吐和肌肉酸痛。阳性组的白细胞(WBC)、淋巴细胞(LYM)、嗜酸性粒细胞(EOS)、血小板(PLT)、C反应蛋白(CRP)和淋巴细胞/单核细胞(LMR)水平低于阴性组,而中性粒细胞(NEU)和单核细胞(MON)水平高于阴性组(P48 h),PLT和LMR水平降低是甲流患者的独立危险因素。
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引用次数: 0
Isolation and genome characterization of a Klebsiella pneumoniae clinical strain carrying blaNDM-5 and blaOXA-48 isolated in Italy. 在意大利分离到的携带 blaNDM-5 和 blaOXA-48 的肺炎克雷伯氏菌临床菌株的分离和基因组特征。
IF 1.5 4区 医学 Q4 MICROBIOLOGY Pub Date : 2024-11-01
Stefano Amadesi, Erica Diani, Annarita Mazzariol, Davide Gibellini, Paolo Gaibani

Carbapenemase-producing Enterobacteriales (CPE) represent an emerging threat for global public health and a serious problem for clinicians due to the limited available treatment options. The emergence of CPE has been recently described worldwide by describing different antimicrobial mechanisms. Here, we describe a CPE carrying dual-carbapenemase isolated in Italy and we provide a deep characterization of the antimicrobial resistance genes, virulence-factors and prophage regions within the genome.

产碳青霉烯酶肠杆菌(CPE)是全球公共卫生面临的一个新威胁,也是临床医生面临的一个严重问题,因为可用的治疗方案有限。最近,世界各地通过描述不同的抗菌机制来描述 CPE 的出现。在此,我们描述了在意大利分离到的一种携带双碳酸烯酵素酶的 CPE,并对其基因组中的抗菌耐药基因、毒力因子和噬菌体区域进行了深入分析。
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引用次数: 0
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New Microbiologica
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