Bacterial Infections

细菌感染
  • 文章类型: Journal Article
    准确识别骨科感染的病因对于正确及时的临床管理非常重要,但是研究很少。在当前的研究中,我们探索了多种细菌病原体与骨科感染的关联。
    住院的骨科患者在青岛的一家乡村医院登记,中国。收集伤口或渗出物拭子样品,并通过培养和多重实时PCR测试十二种细菌病原体。
    共纳入349例骨科住院患者,其中193例入院时出现感染表现,156例无感染迹象。骨科感染患者主要为男性(72.5%),住院时间较长(中位数为15天)。在42.5%(82/193)的感染患者中至少检测到一种病原体,在没有感染的患者中至少检测到一种病原体(P<0.001)。金黄色葡萄球菌是最常见的病原体(15.5%)。观察到数量依赖性病原体与感染的关联,特别是铜绿假单胞菌和肺炎克雷伯菌,可能提示亚临床感染.大多数检测到病原体的患者都有骨科手术史(比值比2.8,P=0.038)。有病原体特异性临床表现。多重qPCR,因为它的高灵敏度,优越的特异性,强大的定量可以与培养结合使用,以指导抗菌治疗并跟踪治疗期间骨科感染的进展。
    UNASSIGNED: Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the current study we explored the association of multiple bacterial pathogens with orthopedic infection.
    UNASSIGNED: Hospitalized orthopedic patients were enrolled in a rural hospital in Qingdao, China. Wound or exudate swab samples were collected and tested for twelve bacterial pathogens with both culture and multiplex real time PCR.
    UNASSIGNED: A total of 349 hospitalized orthopedic patients were enrolled including 193 cases presenting infection manifestations upon admission and 156 with no sign of infection. Orthopedic infection patients were mainly male (72.5%) with more lengthy hospital stay (median 15 days). At least one pathogen was detected in 42.5% (82/193) of patients with infection while 7.1% (11/156) in the patients without infection (P < 0.001). S. aureus was the most prevalent causative pathogen (15.5%). Quantity dependent pathogen association with infection was observed, particularly for P. aeruginosa and K. pneumoniae, possibly indicating subclinical infection. Most of the patients with detected pathogens had a previous history of orthopedic surgery (odds ratio 2.8, P = 0.038). Pathogen specific clinical manifestations were characterized. Multiplex qPCR, because of its high sensitivity, superior specificity, and powerful quantification could be utilized in combination with culture to guide antimicrobial therapy and track the progression of orthopedic infection during treatment.
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  • 文章类型: Journal Article
    坏死,最近发现的一种不同于细胞凋亡的细胞程序性死亡形式,已被证实在各种动物模型的细菌感染的发病机理中起重要作用。坏死对宿主有利,但在某些情况下,这可能是有害的。了解坏死性凋亡对细菌感染发病机制的影响,本文就不同细菌感染引起细胞坏死性凋亡的作用及分子机制进行综述。
    Necroptosis, a recently discovered form of cell-programmed death that is distinct from apoptosis, has been confirmed to play a significant role in the pathogenesis of bacterial infections in various animal models. Necroptosis is advantageous to the host, but in some cases, it can be detrimental. To understand the impact of necroptosis on the pathogenesis of bacterial infections, we described the roles and molecular mechanisms of necroptosis caused by different bacterial infections in this review.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients.
    METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared.
    RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46,P =0.50; χ2=0.03,P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04,P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00,P =0.09; t =0.94,P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53,P =0.47).
    CONCLUSIONS: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.
    UNASSIGNED: 左氧氟沙星联合G-CSF或仅用G-CSF支持疗法在预防自体造血干细胞移植感染中的作用.
    UNASSIGNED: 探讨重组人粒细胞集落刺激因子(G-CSF)联合左氧氟沙星或仅用G-CSF支持疗法在预防自体造血干细胞移植感染中的作用,分析移植患者住院时间、住院费用及移植后生存情况。.
    UNASSIGNED: 回顾性分析2012年1月至2022年7月于本院就诊的接受自体造血干细胞移植的恶性血液病患者,观察自体造血干细胞移植期间左氧氟沙星+G-CSF预防感染组和G-CSF支持组中性粒细胞缺乏伴发热、细菌感染发生率及静脉抗菌药物使用情况,并比较两组住院时间、住院期间总费用及移植90天后存活情况。.
    UNASSIGNED: 102例患者纳入研究,其中多发性骨髓瘤54例,急性白血病36例,淋巴瘤7例,骨髓增生异常综合征3例,轻链型淀粉样变性1例,POEMS综合征1例。47例接受G-CSF+左氧氟沙星预防感染,55例接受G-CSF支持治疗。左氧氟沙星+G-CSF组中40例(85.11%)发生中性粒细胞缺乏伴发热,13例(27.66%)明确为细菌感染。G-CSF组中44例(80.00%)发生中性粒细胞缺乏伴发热,16例(29.09%)细菌感染。两组中性粒细胞缺乏伴发热和细菌感染发生率均无统计学差异(χ2=0.46,P =0.50;χ2=0.03,P =0.87)。左氧氟沙星+G-CSF组静脉抗菌药物使用率为85.11%(40/47),与G-CSF组的85.45%(47/55)比较无统计学差异(χ2= 0.04,P =0.84)。左氧氟沙星+G-CSF组与G-CSF组左氧氟沙星耐药菌的检出率分别为8.57%(3/35)和21.43%(6/ 28),无统计学差异(χ2=0.65,P >0.05)。左氧氟沙星+G-CSF与G-CSF组患者住院中位时间为25 d vs 22 d,住院中位费用为78 216.24元 vs 80 724.38元,差异均无统计学意义( t =3.00,P =0.09; t =0.94,P =0.09)。移植后90天内,左氧氟沙星+G-CSF组有2例(4.26%)死亡,G-CSF组有1例(1.82%)死亡,两组比较无统计学差异(χ2=0.53,P =0.47)。.
    UNASSIGNED: 较G-CSF支持相比,患者在自体造血干细胞移植期间应用G-CSF+左氧氟沙星预防感染无明显获益。.
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  • 文章类型: Journal Article
    巨噬细胞具有不同范围的明确定义的能力和作为吞噬细胞的作用,包括炎症的调节,促进伤口愈合,维持组织稳态,并作为针对微生物病原体的先天免疫应答的关键因素。细胞外陷阱的出现是一种新的防御策略,已在几种类型的先天免疫细胞中观察到。为了应对感染,巨噬细胞被刺激并产生巨噬细胞胞外陷阱(MET),采取网状结构的形式,充满DNA链,装饰有组蛋白和其他细胞蛋白。MET不仅捕获和消除微生物,而且在某些疾病如炎症和自身免疫性疾病的发展中起作用。这项研究的主要目的是研究MET在解决细菌感染方面的最新进展。我们还深入研究了细菌用来逃避或忍受MET影响的现有知识和策略。通过这次调查,我们希望阐明细菌和宿主免疫系统之间复杂的相互作用,特别是在MET的杀微生物效应机制的背景下。对MET的持续探索及其对宿主防御各种病原体的影响为理解和潜在操纵免疫系统对感染的反应开辟了新的途径。
    Macrophages possess a diverse range of well-defined capabilities and roles as phagocytes, encompassing the regulation of inflammation, facilitation of wound healing, maintenance of tissue homeostasis, and serving as a crucial element in the innate immune response against microbial pathogens. The emergence of extracellular traps is a novel strategy of defense that has been observed in several types of innate immune cells. In response to infection, macrophages are stimulated and produce macrophage extracellular traps (METs), which take the form of net-like structures, filled with strands of DNA and adorned with histones and other cellular proteins. METs not only capture and eliminate microorganisms but also play a role in the development of certain diseases such as inflammation and autoimmune disorders. The primary objective of this study is to examine the latest advancements in METs for tackling bacterial infections. We also delve into the current knowledge and tactics utilized by bacteria to elude or endure the effects of METs. Through this investigation, we hope to shed light on the intricate interactions between bacteria and the host\'s immune system, particularly in the context of microbicidal effector mechanisms of METs. The continued exploration of METs and their impact on host defense against various pathogens opens up new avenues for understanding and potentially manipulating the immune system\'s response to infections.
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  • 文章类型: Journal Article
    迫切需要针对难以治疗的细菌感染的新治疗策略,更快、更便宜的方法可能是重新利用现有的抗生素。纳米递送系统通过引导抗生素到达其靶标来增强抗生素的功效,增加感染部位的局部浓度。虽然最近描述的纳米递送系统是有前途的,它们通常不容易适应不同的目标,缺乏生物相容性或特异性。这里,纳米递送系统从噬菌体中获得靶向蛋白。噬菌体受体结合蛋白和细胞壁结合域与纳米颗粒结合,有针对性地运送利福平,亚胺培南,和氨苄青霉素对抗细菌病原体。它们对它们的靶标表现出极好的特异性,并积聚在感染部位以提供其抗生素有效载荷。此外,纳米递送系统比游离抗生素剂量高16至32倍更有效地抑制病原体感染.这项研究表明,噬菌体来源的靶向蛋白是指导纳米递送系统的有希望的候选物。他们的特殊性,可用性,和生物相容性使它们成为指导抗生素纳米递送系统的绝佳选择,这些系统迫切需要对抗难以治疗的感染。
    Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.
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  • 文章类型: Journal Article
    细菌感染和随之而来的杀菌剂抗性问题的爆发对全球健康和农产品都是致命的威胁。因此,探索具有新作用机制的候选杀菌剂至关重要。丝状温度敏感突变Z(FtsZ)蛋白已被认为是新的杀菌剂发现的新的有希望和有效的靶标。因此,使用跳台策略,我们设计了新的7H-吡咯并[2,3-d]嘧啶衍生物,评估了它们的抗菌活性,并研究了它们的结构-活动关系。其中,化合物B6对米黄单胞菌pv表现出最佳的体外生物活性(EC50=4.65µg/mL)。稻米(Xoo),优于参考文献(双甲噻唑[BT],EC50=48.67µg/mL;噻二唑铜[TC],EC50=98.57µg/mL]。此外,通过GTP酶活性测定验证了化合物B6靶向FtsZ的效力,FtsZ自组装观察,荧光滴定,傅里叶变换红外光谱(FT-IR)分析,分子动力学模拟,和形态学观察。GTP酶活性测定显示化合物B6对XooFtsZ的最终IC50值为235.0μM。有趣的是,GTP酶活性结果表明B6-XooFtsZ复合物具有优异的结合常数(KA=103.24M-1)。总的来说,抗菌行为表明B6可以与XooFtsZ相互作用并抑制其GTP酶活性,导致细菌细胞伸长甚至死亡。此外,化合物B6在体内表现出可接受的抗Xoo活性和低毒性,并通过ADMET分析预测了良好的药代动力学特征。我们的发现为FtsZ抑制剂的开发提供了新的化学类型,以及对其潜在作用机制的见解。
    Bacterial infections and the consequent outburst of bactericide-resistance issues are fatal menace to both global health and agricultural produce. Hence, it is crucial to explore candidate bactericides with new mechanisms of action. The filamenting temperature-sensitive mutant Z (FtsZ) protein has been recognized as a new promising and effective target for new bactericide discovery. Hence, using a scaffold-hopping strategy, we designed new 7H-pyrrolo[2,3-d]pyrimidine derivatives, evaluated their antibacterial activities, and investigated their structure-activity relationships. Among them, compound B6 exhibited the optimal in vitro bioactivity (EC50 = 4.65 µg/mL) against Xanthomonas oryzae pv. oryzae (Xoo), which was superior to the references (bismerthiazol [BT], EC50 = 48.67 µg/mL; thiodiazole copper [TC], EC50 = 98.57 µg/mL]. Furthermore, the potency of compound B6 in targeting FtsZ was validated by GTPase activity assay, FtsZ self-assembly observation, fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR) assay, molecular dynamics simulations, and morphological observation. The GTPase activity assay showed that the final IC50 value of compound B6 against XooFtsZ was 235.0 μM. Interestingly, the GTPase activity results indicated that the B6-XooFtsZ complex has an excellent binding constant (KA = 103.24 M-1). Overall, the antibacterial behavior suggests that B6 can interact with XooFtsZ and inhibit its GTPase activity, leading to bacterial cell elongation and even death. In addition, compound B6 showed acceptable anti-Xoo activity in vivo and low toxicity, and also demonstrated a favorable pharmacokinetic profile predicted by ADMET analysis. Our findings provide new chemotypes for the development of FtsZ inhibitors as well as insights into their underlying mechanisms of action.
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  • 文章类型: Journal Article
    细菌生物膜通常在人类中引起慢性和持续性感染。细菌生物膜由细菌的内层和自分泌的细胞外聚合物(EPS)组成。生物膜分散剂(缩写为分散剂)已证明可有效去除细菌物理保护屏障EPS。分散剂通常较弱或没有杀菌作用。从生物膜中分散的细菌(缩写为分散细菌)可能更具侵袭性,粘合剂,比浮游细菌更能动,增加分散细菌重新定殖并引起再感染的可能性的特征。分散剂应与抗微生物剂联合使用,以避免严重再感染的风险。基于分散剂的纳米颗粒具有特异性释放和强烈渗透的优势,为进一步发挥抗菌剂的功效和实现生物膜的根除提供了前提。预期用于治疗与细菌生物膜感染相关的疾病的基于分散剂的纳米颗粒递送的抗微生物剂是防止由分散的细菌引起的再感染的有效措施。关键点:•讨论了分散细菌的危害和分散剂的分散机理。•讨论了基于分散剂的纳米颗粒在细菌生物膜中的优势。•突出了用于阻断体内再感染的基于分散剂的纳米颗粒。
    Bacterial biofilms commonly cause chronic and persistent infections in humans. Bacterial biofilms consist of an inner layer of bacteria and an autocrine extracellular polymeric substance (EPS). Biofilm dispersants (abbreviated as dispersants) have proven effective in removing the bacterial physical protection barrier EPS. Dispersants are generally weak or have no bactericidal effect. Bacteria dispersed from within biofilms (abbreviated as dispersed bacteria) may be more invasive, adhesive, and motile than planktonic bacteria, characteristics that increase the probability that dispersed bacteria will recolonize and cause reinfection. The dispersants should be combined with antimicrobials to avoid the risk of severe reinfection. Dispersant-based nanoparticles have the advantage of specific release and intense penetration, providing the prerequisite for further antibacterial agent efficacy and achieving the eradication of biofilms. Dispersant-based nanoparticles delivered antimicrobial agents for the treatment of diseases associated with bacterial biofilm infections are expected to be an effective measure to prevent reinfection caused by dispersed bacteria. KEY POINTS: • Dispersed bacteria harm and the dispersant\'s dispersion mechanisms are discussed. • The advantages of dispersant-based nanoparticles in bacteria biofilms are discussed. • Dispersant-based nanoparticles for cutting off reinfection in vivo are highlighted.
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  • 文章类型: Editorial
    微生物生物膜是慢性和复发性感染的最重要驱动因素[。..].
    Microbial biofilms are the most important drivers of chronic and recurrent infections [...].
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  • 文章类型: Journal Article
    细菌感染是伤口愈合中最常见的并发症,强调迫切需要开发创新的抗菌技术和治疗方法,以应对细菌感染带来的日益增长的威胁。黑磷纳米片(BPNS),作为一种有前途的二维纳米材料,已用于治疗感染的伤口。然而,BP的有限稳定性限制了其应用。在这项研究中,我们通过将镓离子(Ga3+)锚定在BP表面来增强BP的稳定性和抗菌性能,创造了一个新颖的抗菌平台。这种修饰降低了BP的电子密度并通过协同作用增强了其抗菌能力。在近红外(NIR)照射下,BP/Ga3+组合通过光热疗法(PTT)和光动力疗法(PDT)发挥抗菌作用,同时也释放Ga3+。Ga3+采用“特洛伊木马策略”来破坏铁代谢,显着增强复合物的抗菌功效。这种创新材料为抗生素提供了可行的替代品,并在治疗感染伤口和帮助皮肤重建方面具有重要的前景。
    Bacterial infection is the most common complication in wound healing, highlighting an urgent need for the development of innovative antibacterial technologies and treatments to address the growing threats posed by bacterial infections. Black phosphorus nanosheets (BPNSs), as a promising two-dimensional nanomaterial, have been utilized in treating infected wounds. However, BP\'s limited stability restricts its application. In this study, we enhance BP\'s stability and its antibacterial properties by anchoring gallium ions (Ga3+) onto BP\'s surface, creating a novel antibacterial platform. This modification reduces BP\'s electron density and enhances its antibacterial capabilities through a synergistic effect. Under near-infrared (NIR) irradiation, the BP/Ga3+ combination exerts antibacterial effects via photothermal therapy (PTT) and photodynamic therapy (PDT), while also releasing Ga3+. The Ga3+ employ a \'Trojan horse strategy\' to disrupt iron metabolism, significantly boosting the antibacterial efficacy of the complex. This innovative material offers a viable alternative to antibiotics and holds significant promise for treating infected wounds and aiding skin reconstruction.
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  • 文章类型: Journal Article
    细菌感染是全世界新生儿发病和死亡的主要原因之一。寻找用于细菌感染的早期识别和诊断以及抗菌药物施用的早期个体化的快速和可靠的方法对于根除这些感染和预防严重的并发症至关重要。然而,由于非特异性临床表现,这通常很难执行,当前诊断方法的准确性低,和新生儿药代动力学知识有限。尽管新生儿医学接受机器学习(ML)的好处相对较晚,已经有一些初步应用ML早期预测新生儿败血症和抗生素个体化。本文简要介绍了ML,并讨论了诊断和治疗新生儿细菌感染的最新技术,间隙,ML的潜在用途,以及解决当前研究局限性的未来方向。新生儿细菌感染涉及生理发育的组合,疾病表达,和治疗反应结果。为了解决这种复杂的关系,未来的模型可以考虑适当的ML算法来捕获时间序列特征,同时整合来自主机的影响,微生物,以及优化新生儿抗菌药物使用的药物。所有模型在临床使用前都需要前瞻性临床试验来验证其临床实用性。
    Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.
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