Antibiotic resistance

抗生素耐药性
  • 文章类型: Journal Article
    医疗保健相关感染(HCAI)构成了重大挑战,影响患者安全和治疗效果。这项回顾性研究调查了ICU心脏手术患者术前住院时间与HCAI之间的相关性。
    分析了35例ICU心脏手术后死亡患者的病历,关注术前住院时间。
    术前停留时间延长(r=0.993)与HCAI升高密切相关,表明了一个关键的风险因素。
    术前住院时间对HCAI风险至关重要。需要前瞻性多中心研究进行验证,这对于提高患者安全性和治疗效果至关重要。
    UNASSIGNED: Healthcare-associated infections (HCAIs) pose a significant challenge, impacting patient safety and treatment effectiveness. This retrospective study investigates the correlation between pre-operative hospital stays and HCAIs in ICU cardiac surgery patients.
    UNASSIGNED: Medical records of 35 patients who died post-cardiac surgery in the ICU were analyzed, focusing on the duration of pre-operative hospitalization.
    UNASSIGNED: Prolonged pre-operative stays strongly correlate (r = 0.993) with increased HCAIs, indicating a critical risk factor.
    UNASSIGNED: The duration of pre-operative hospital stays is pivotal in HCAI risk. Prospective multicenter studies are needed for validation, which is crucial for enhancing patient safety and treatment efficacy.
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  • 文章类型: Journal Article
    引言肺结核(TB)仍然是全球健康问题,结核分枝杆菌广泛耐药(XDR)菌株的出现加剧了这种情况。本研究采用先进的分子技术,特别是聚合酶链反应(PCR)分析,全面表征诊断为肺结核患者XDR病原菌的遗传格局。该研究的目的是通过应用PCR阐明与肺结核菌株耐药性相关的基因,并分析有助于对多种药物产生耐药性的特定遗传基因座。材料和方法从Saveetha医学院和医院的三级医疗机构收集了总共116例疑似结核病的临床样本,以鉴定MTB。其中包括痰(n=35),鼻拭子(n=17),血液(n=44),支气管肺泡灌洗(BAL)(n=20)。处理收集的样本并进行DNA提取。根据协议,进行DNA沉淀的重建。将重构的DNA储存在-20°C用于PCR测定。从获得的阳性样本样本中,XDR肺结核标本集中于靶向基因,特别是利福平抗性的rpoB基因,inhA,和katG基因为异烟肼抗性的启动子区。结果在总共获得的116个样本中,53例肺结核检测呈阳性,指示分枝杆菌感染。在这些积极的案例中,43名患者在三级医疗机构接受了治疗。随后,用提取的目标基因rpoB的DNA进行PCR测定,inhA,还有KatG.具体来说,22个痰样本显示rpoB基因表达,inhA,还有KatG,而9个鼻拭子显示rpoB和inhA基因的表达。此外,在7份血液标本中检测到rpoB基因表达,rpoB和inhA基因在五个BAL样品中均表达。结论采用先进和快速的分子检测和口服给药方案可以促进XDR-TB的快速诊断和有效治疗。利用新开发和重新利用的抗结核药物,如pretomanid,bedaquiline,利奈唑胺,和乙二甲酰胺.坚持这些建议有望有效管理广泛耐药结核病。然而,进行精心设计的临床试验和研究,以进一步评估新药和较短的治疗方案的疗效,从而确保持续改进这一具有挑战性的条件的管理。
    Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. This study employs advanced molecular techniques, specifically polymerase chain reaction (PCR) profiling, to comprehensively characterize the genetic landscape of XDR pathogenic bacteria in patients diagnosed with pulmonary TB. The objective of the study is to elucidate the genes that are associated with drug resistance in pulmonary TB strains through the application of PCR and analyze specific genetic loci that contribute to the development of resistance against multiple drugs. Materials and methods A total of 116 clinical samples suspected of TB were collected from the tertiary healthcare setting of Saveetha Medical College and Hospitals for the identification of MTB, which includes sputum (n = 35), nasal swabs (n = 17), blood (n = 44), and bronchoalveolar lavage (BAL) (n = 20). The collected specimens were processed and subjected to DNA extraction. As per the protocol, reconstitution of the DNA pellet was carried out. The reconstituted DNA was stored at -20 °C for the PCR assay. From the obtained positive sample specimens, XDR pulmonary TB specimens were focused on the targeted genes, specifically the rpoB gene for rifampicin resistance, inhA, and katG gene for thepromoter region for isoniazid resistance. Results Out of a total of 116 samples obtained, 53 tested positive for pulmonary TB, indicative of a mycobacterial infection. Among these positive cases, 43 patients underwent treatment at a tertiary healthcare facility. Subsequently, a PCR assay was performed with the extracted DNA for the target genes rpoB, inhA, and katG. Specifically, 22 sputum samples exhibited gene expression for rpoB, inhA, and katG, while nine nasal swabs showed expression of the rpoB and inhA genes. Additionally, rpoB gene expression was detected in seven blood specimens, and both rpoB and inhA genes were expressed in five BAL samples. Conclusion The swift diagnosis and efficient treatment of XDR-TB can be facilitated by employing advanced and rapid molecular tests and oral medication regimens. Utilizing both newly developed and repurposed anti-TB drugs like pretomanid, bedaquiline, linezolid, and ethionamide. Adhering to these current recommendations holds promise for managing XDR-TB effectively. Nevertheless, it is significant to conduct well-designed clinical trials and studies to further evaluate the efficacy of new agents and shorter treatment regimens, thus ensuring continuous improvement in the management of this challenging condition.
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  • 文章类型: Journal Article
    背景:本研究调查了粪肠球菌中利奈唑胺和万古霉素敏感性的分布和特征(E.粪肠球菌)和屎肠球菌(E.faecium)并探索了潜在的抗性机制。
    方法:回顾性收集2842株肠球菌临床分离株,并对其临床资料进行进一步分析。通过肉汤稀释法验证万古霉素和利奈唑胺的最低抑制浓度(MIC)。抗性基因optrA,cfr,vana,使用聚合酶链反应(PCR)研究vanB和vanM。通过全基因组测序(WGS)获得管家基因和抗性基因。
    结果:在2842株肠球菌分离物中,88.5%(2516)来自尿液,其中屎肠球菌占60.1%。在27/28耐万古霉素肠球菌(VRE)分离株中鉴定出vanA基因,其中4个携带vanA和vanM基因。剩余的菌株为vanM阳性。在利奈唑胺抗性肠球菌(LRE)中的所有粪肠球菌分离物中鉴定了optrA基因。与粪肠球菌相比,粪肠球菌显示出更高的多重抗生素抗性指数(MAR指数)。多位点序列分型(MLST)显示屎肠球菌的序列类型主要属于克隆复合体(CC)17种,分析的近屎肠球菌分离株分为7种特征序列类型(STs),其中CC16的ST16是主要谱系。
    结论:本研究中,尿液是VRE和LRE分离株的主要来源。与粪肠球菌相比,粪肠球菌表现出更高的抗性水平。在91.6%的LRE中检测到OptrA基因,这可以解释利奈唑胺耐药,在所有耐万古霉素肠球菌菌株中检测到van基因,而vanA是本研究确定的VRE的关键耐药机制。
    BACKGROUND: This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms.
    METHODS: A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS).
    RESULTS: Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage.
    CONCLUSIONS: Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
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  • 文章类型: Journal Article
    背景:尿路感染(UTI)在其一生中影响所有女性的近三分之二,并且许多经历复发性感染。有来自多个国际协会的基于证据的评估和治疗指南;然而,最近基于索赔的分析表明,这些指南的依从性很差。本研究旨在了解美国初级保健提供者(PCP)在为UTI和复发性UTI(rUTI)提供基于指南的护理方面遇到的障碍。
    方法:18个PCP的半结构化访谈,从大洛杉矶地区招募的,检查了UTI/rUTI发作的真实世界临床管理,决定参考亚专科护理,和资源指导咨询和管理。扎根理论方法可用于分析访谈笔录并确定初步和主要主题。
    结果:参与者表示希望获得每次膀胱炎发作的尿液培养物,但由于患者的要求或护理障碍而感到有压力做出妥协。如果患者有rUTI病史,PCP的经验性治疗阈值较低,年纪大了,或拒绝评估。实验室数据在临床决策中的利用最少:在解释培养数据时很少考虑尿液分析。PCP治疗广泛的泌尿系统和非泌尿系统症状作为UTI,即使是负面文化。PCP在开始UTI预防时感觉不舒服,而是寻求解剖原因的专家评估。他们不知道管理指南,通常使用UpToDate®作为其主要资源。提供者很少推荐基于证据的UTI预防干预措施。
    结论:简洁清晰的专业指南的低可用性是适当UTI/rUTI护理的重大障碍。临床指导文件的可用性差导致对预防措施和额外诊断测试的作用的严重混淆。患者获得护理提供者的困难导致对推定治疗的期望。需要进一步的研究来确定是否为提供者和/或管理算法提供改进的教育材料可以改善UTI管理的指南一致性。
    BACKGROUND: Urinary tract infections (UTI) affect almost two-thirds of all women during their lives and many experience recurrent infections. There are evidence-based guidelines from multiple international societies for evaluation and treatment; however, recent claims-based analyses have demonstrated that adherence to these guidelines is poor. This study seeks to understand the barriers experienced by U.S. primary care providers (PCPs) to providing guideline-based care for UTI and recurrent UTI (rUTI).
    METHODS: Semi-structured interviews of 18 PCPs, recruited from the greater Los Angeles area, examined real-world clinical management of UTI/rUTI episodes, decisions to refer to subspecialty care, and resources guiding counseling and management. Grounded theory methodology served to analyze interview transcripts and identify preliminary and major themes.
    RESULTS: Participants expressed the desire to obtain urine cultures for each cystitis episode, but felt pressured to make compromises by patient demands or barriers to care. PCPs had lower thresholds to empirical treatment if patients had a history of rUTIs, were elderly, or declined evaluation. Laboratory data was minimally utilized in clinical decision-making: urinalyses were infrequently considered when interpreting culture data. PCPs treated a broad set of urologic and non-urologic symptoms as UTI, even with negative cultures. PCPs did not feel comfortable initiating UTI prophylaxis, instead seeking specialist evaluation for anatomic causes. They were unaware of management guidelines, typically utilizing UpToDate® as their primary resource. Few evidence-based UTI prevention interventions were recommended by providers.
    CONCLUSIONS: Low availability of succinct and clear professional guidelines are substantial barriers to appropriate UTI/rUTI care. Poor useability of clinical guidance documents results in substantial confusion about the role of preventative measures and additional diagnostic testing. Difficulties in patient access to care providers lead to expectations for presumptive treatment. Future studies are needed to determine if improved educational materials for providers and/or management algorithms can improve guideline concordance of UTI management.
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  • 文章类型: Journal Article
    胃肠道感染每年影响许多人。这些感染中最常见的细菌是肠道致病菌,并且在继续使用广谱抗生素时,涉及艰难梭菌相关性腹泻,尤其是住院患者。本研究的目的是研究肠致病菌对抗生素的耐药性。
    在这项横断面研究中,检查了DezfulGanjavian医院的163例腹泻患者样本。样品在MacConkey中培养,Hektoen肠琼脂和GN肉汤,和环丝氨酸头孢西丁果糖琼脂培养基,并在标准条件下孵育。为了鉴定肠道致病菌,使用生化试验和血清学确认试验。通过Kirby-Bauer纸片扩散敏感性试验研究了分离株的抗生素耐药性。
    病原菌的发生频率包括41.1%的福氏志贺氏菌,其次是S.sonnei的41.1%,6.7%的肠致病性大肠杆菌,5.5%的肠道沙门氏菌血清群B,和5.5%的痢疾志贺氏菌。结果显示,共有46例患者有关于艰难梭菌培养的医嘱,没有从样品中分离出艰难梭菌。研究的分离株对甲氧苄啶-磺胺甲恶唑的抗性最高,头孢曲松(88.3%),治疗患者最有效的抗生素是环丙沙星,其敏感性为86%。
    分离株对抗生素的敏感性不同,这表明,早期识别感染剂和选择正确的抗生素治疗对改善胃肠道感染和防止感染传播是有效的。
    UNASSIGNED: Gastrointestinal infections affect many people annually. The most common bacterial agents involved in these infections are enteropathogenic bacteria and in the continuation of using broad-spectrum antibiotics, Clostridium difficile-associated diarrhea is involved, especially in hospitalized patients. The aim of the present study was to investigate the pattern of antibiotic resistance among enteropathogenic bacteria.
    UNASSIGNED: In this cross-sectional study, 163 samples of patients with diarrhea in Dezful Ganjavian Hospital were examined. The samples were cultured in MacConkey, Hektoen enteric agar and GN broth, and cycloserine cefoxitin fructose agar media and incubated under standard conditions. In order to identify enteropathogenic bacteria, biochemical tests and serological confirmatory tests were used. Antibiotic resistance pattern of the isolates was investigated by Kirby-Bauer disk diffusion susceptibility test.
    UNASSIGNED: The frequency of pathogenic bacteria includes 41.1% of Shigella flexneri, followed by 41.1% of S. sonnei, 6.7% of Enteropathogenic E. coli, 5.5% of Salmonella enterica Serogroup B, and 5.5% of Shigella dysenteriae. The results revealed a total of 46 patients with orders regarding C. difficile culture, no C. difficile was isolated from the samples. The studied isolates showed the highest resistance to trimethoprim-sulfamethoxazole, and ceftriaxone (88.3%), and the most effective antibiotic in the treatment of patients was ciprofloxacin with 86% sensitivity.
    UNASSIGNED: Susceptibility to antibiotics was different among the isolates, which shows that the early identification of the infection agent and the selection of the correct antibiotic treatment are effective in improving the gastrointestinal infection and preventing the spread of the infection.
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  • 文章类型: Journal Article
    新的抗菌策略的探索是由引起严重公共卫生问题的抗生素抗性微生物推动的。近年来,纳米级材料已经发展成为对抗感染的替代方法。尽管许多纳米材料被发现是有害的,许多研究人员对由银等贵金属制成的纳米颗粒(NPs)表现出浓厚的兴趣,黄金和铂金。为了从植物中制造环境安全的NP,绿色化学和纳米技术结合起来解决了毒性问题。在过去的10年中,双金属纳米粒子(BNPs)的研究得到了极大的发展。由天然提取物介导的BNP的产生是简单的,低成本和环保。由于其低毒性,安全性和生物稳定性,高贵的BNP与银,黄金,铂和钯具有用于生物医学应用的潜力。它们对人类健康有重大影响,由于其生物学特性而被用于医学和药学,其中包括催化,抗氧化剂,抗菌,抗糖尿病药,抗癌,保肝和再生活性。
    The exploration of newer antibacterial strategies is driven by antibiotic-resistant microbes that cause serious public health issues. In recent years, nanoscale materials have developed as an alternative method to fight infections. Despite the fact that many nanomaterials have been discovered to be harmful, numerous researchers have shown a keen interest in nanoparticles (NPs) made of noble metals like silver, gold and platinum. To make environmentally safe NPs from plants, green chemistry and nanotechnology have been combined to address the issue of toxicity. The study of bimetallic nanoparticles (BNPs) has increased tremendously in the past 10 years. The production of BNPs mediated by natural extracts is straightforward, low cost and environmentally friendly. Due to their low toxicity, safety and biological stability, noble BNPs with silver, gold, platinum and palladium have the potential to be used in biomedical applications. They have a significant impact on human health and are used in medicine and pharmacy due to their biological characteristics, which include catalytic, antioxidant, antibacterial, antidiabetic, anticancer, hepatoprotective and regenerative activity.
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  • 文章类型: Journal Article
    鲍曼不动杆菌(A.鲍曼不动杆菌)是临床上引起医院感染的重要机会性病原体。抗生素耐药性的发生率逐年上升,导致严重的细菌耐药性。
    为了更好地了解多药耐药鲍曼不动杆菌的当地流行病学,研究了不同类型鲍曼不动杆菌的耐药性及其与鲍曼不动杆菌基因的关系。此外,通过转录组分析研究鲍曼不动杆菌耐药性的分子机制。
    这些结果表明,共检测到9个ST。结果发现,在医院中分离出的99%的菌株属于相同的STs,克隆复合体CC208广泛分布于各个部门和各类样品中。此外,这些鲍曼不动杆菌菌株对厄他培南表现出很高的抗性,比阿培南,美罗培南,还有亚胺培南,其中对厄他培南的抵抗力最强。blaOXA-51基因在这些耐碳青霉烯类鲍曼不动杆菌(CRAB)中的检出率达到100%;转录组结果表明,抗性菌株中的抗性基因上调,这些参与生物膜形成的基因,外排泵,肽聚糖生物合成,和伴奏蛋白合成。
    这些结果表明,CC208STs是主要的克隆复合物,并表现出高的碳青霉烯类抗生素耐药性。所有这些耐药菌株分布在各个部门,但其中大部分分布在重症监护病房(ICU).BlaOXA-23是主要的抗生素抗性基因型;总之,贵阳市鲍曼不动杆菌临床流行趋势,从分子水平分析中国,用转录组分析鲍曼不动杆菌对碳青霉烯类抗生素的耐药机制,为更好地控制鲍曼不动杆菌提供了理论依据。
    UNASSIGNED: Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting in a highly serious situation of bacterial resistance.
    UNASSIGNED: To better understand the local epidemiology of multidrug-resistant A. baumannii, an investigation was conducted on the antibiotic resistance of different types of A. baumannii and its relationship with the genes of A. baumannii. Furthermore, the molecular mechanism underlying antibiotic resistance in A. baumannii was investigated through transcriptome analysis.
    UNASSIGNED: These results showed that a total of 9 STs were detected. It was found that 99% of the strains isolated in the hospital belonged to the same STs, and the clone complex CC208 was widely distributed in various departments and all kinds of samples. Furthermore, these A. baumannii strains showed high resistance to ertapenem, biapenem, meropenem, and imipenem, among which the resistance to ertapenem was the strongest. The detection rate of bla OXA-51 gene in these carbapenem resistance A. baumannii (CRAB) reached 100%; Additionally, the transcriptome results showed that the resistance genes were up-regulated in resistance strains, and these genes involved in biofilm formation, efflux pumps, peptidoglycan biosynthesis, and chaperonin synthesis.
    UNASSIGNED: These results suggest that the CC208 STs were the main clonal complex, and showed high carbapenem antibiotic resistance. All these resistant strains were distributed in various departments, but most of them were distributed in intensive care units (ICU). The bla OXA-23 was the main antibiotic resistance genotype; In summary, the epidemic trend of clinical A. baumannii in Guiyang, China was analyzed from the molecular level, and the resistance mechanism of A. baumannii to carbapenem antibiotics was analyzed with transcriptome, which provided a theoretical basis for better control of A. baumannii.
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  • 文章类型: Journal Article
    复方新诺明,磺胺甲恶唑和甲氧苄啶的联合制剂,是几种传染病的首选治疗方法之一,尤其是尿路感染。复方新诺明的两种成分都是合成抗菌药物,他们的组合在大约半个世纪前被引入医学治疗学。在革兰氏阴性细菌中,对复方新诺明的耐药性很普遍,基于从辅助基因组中获得赋予其每个抗菌成分抗性的基因。从先前对一组耐复方新诺明的尿路致病性大肠杆菌菌株中对磺胺甲恶唑的抗性基因型的认识出发,这项工作的重点是鉴定这些相同菌株的甲氧苄啶抗性的遗传基础。采用的分子技术包括特定扩增子的PCR和Sanger测序,转移质粒的缀合实验和NGS测序。鉴定了赋予甲氧苄啶抗性表型的可移动遗传元件,并包括整合子,转座子和单基因盒。因此,菌株表现出几种联合抵抗两种抗生素的方法,暗示赋予对磺胺甲恶唑(sul)和甲氧苄啶(dfra)抗性的基因之间的遗传连锁水平不同。两个结构特别有趣,因为它们代表了确保耐复方新诺明的高度内聚排列。他们都携带了一个基因盒,dfrA14或dfrA1,集成在保守簇sul2-strA-strB的两个不同点中,进行可转移的质粒。结果表明,复方新诺明对我们环境中的细菌施加的压力仍在促进向日益紧密的基因排列进化,由可移动的遗传因子携带,这些遗传因子在基因组中移动,并在细菌之间水平转移。
    Cotrimoxazole, the combined formulation of sulfamethoxazole and trimethoprim, is one of the treatments of choice for several infectious diseases, particularly urinary tract infections. Both components of cotrimoxazole are synthetic antimicrobial drugs, and their combination was introduced into medical therapeutics about half a century ago. In Gram-negative bacteria, resistance to cotrimoxazole is widespread, being based on the acquisition of genes from the auxiliary genome that confer resistance to each of its antibacterial components. Starting from previous knowledge on the genotype of resistance to sulfamethoxazole in a collection of cotrimoxazole resistant uropathogenic Escherichia coli strains, this work focused on the identification of the genetic bases of the trimethoprim resistance of these same strains. Molecular techniques employed included PCR and Sanger sequencing of specific amplicons, conjugation experiments and NGS sequencing of the transferred plasmids. Mobile genetic elements conferring the trimethoprim resistance phenotype were identified and included integrons, transposons and single gene cassettes. Therefore, strains exhibited several ways to jointly resist both antibiotics, implying different levels of genetic linkage between genes conferring resistance to sulfamethoxazole (sul) and trimethoprim (dfrA). Two structures were particularly interesting because they represented a highly cohesive arrangements ensuring cotrimoxazole resistance. They both carried a single gene cassette, dfrA14 or dfrA1, integrated in two different points of a conserved cluster sul2-strA-strB, carried on transferable plasmids. The results suggest that the pressure exerted by cotrimoxazole on bacteria of our environment is still promoting the evolution toward increasingly compact gene arrangements, carried by mobile genetic elements that move them in the genome and also transfer them horizontally among bacteria.
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  • 文章类型: Journal Article
    使用抗生素可以使人类和动物的消化微生物群暴露于亚抑制浓度,可能有利于抗性细菌的选择。最小选择性浓度(MSC)是理解该过程的关键指标。MSC定义为促进抗性菌株相对于敏感的等基因菌株生长的抗生素的最低浓度。它表示亚最小抑制浓度(MIC)选择窗口的下限,可以选择抗性突变体。以前的研究集中在标准培养条件下确定MSC,而我们的研究旨在确定接近体内条件的模型中的MSC。
    我们研究了Mueller-Hinton肉汤(MHB)中土霉素(OTC)的MSC和来自空肠的灭菌肠内容物(SIC),猪的盲肠和直肠(粪便),使用两种同基因大肠杆菌菌株(一种对OTC敏感,一种对OTC耐药)。此外,测定OTC对易感菌株的MIC,以评估亚MIC选择窗口的上限.
    我们的研究采用了一种新颖的方法,结果表明,MHB的MIC和MSC值均低于SIC。在后者中,这些值根据肠段的不同而不同,远端区室表现出较高的MIC和MSC值。此外,SIC中OTC的亚MIC选择窗口从空肠到直肠变窄,MSC与粪便SIC中的MIC明显更接近。
    结果表明,OTC与消化内容物结合,降低游离OTC的比例。然而,仅仅结合并不能完全解释我们的结果,细菌和肠道内容物之间的相互作用可能起作用。此外,我们的发现提供了低浓度促进肠道耐药性选择的初步估计.最后,这项研究增强了对抗菌素耐药性选择的理解,在评估肠道耐药性发展的风险时,强调抗生素和肠道内容物组成之间复杂的相互作用。
    UNASSIGNED: The administration of antibiotics can expose the digestive microbiota of humans and animals to sub-inhibitory concentrations, potentially favouring the selection of resistant bacteria. The minimal selective concentration (MSC) is a key indicator to understand this process. The MSC is defined as the lowest concentration of an antibiotic that promotes the growth of a resistant strain over a susceptible isogenic strain. It represents the lower limit of the sub-minimal inhibitory concentration (MIC) selective window, where resistant mutants can be selected. Previous studies focused on determining the MSC under standard culture conditions, whereas our research aimed to determine the MSC in a model that approximates in vivo conditions.
    UNASSIGNED: We investigated the MSC of oxytetracycline (OTC) in Mueller-Hinton broth (MHB) and sterilised intestinal contents (SIC) from the jejunum, caecum and rectum (faeces) of pigs, using two isogenic strains of Escherichia coli (one susceptible and one resistant to OTC). Additionally, the MIC of OTC against the susceptible strain was determined to assess the upper limit of the sub-MIC selective window.
    UNASSIGNED: Our study took a novel approach, and the results indicated that MIC and MSC values were lower in MHB than in SIC. In the latter, these values varied depending on the intestinal segment, with distal compartments exhibiting higher MIC and MSC values. Moreover, the sub-MIC selective window of OTC in SIC narrowed from the jejunum to the rectum, with a significantly closer MSC to MIC in faecal SIC.
    UNASSIGNED: The results suggest that OTC binds to digestive contents, reducing the fraction of free OTC. However, binding alone does not fully explain our results, and interactions between bacteria and intestinal contents may play a role. Furthermore, our findings provide initial estimates of low concentrations facilitating resistance selection in the gut. Finally, this research enhances the understanding of antimicrobial resistance selection, emphasising the intricate interplay between antibiotics and intestinal content composition in assessing the risk of resistance development in the gut.
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  • 文章类型: Journal Article
    嗜麦芽窄食单胞菌复合体(Smc)已成为导致死亡率增加的重要医院病原体,特别是在血液感染的情况下。
    这项研究采用全基因组测序(WGS)来评估遗传多样性,抗菌素耐药性概况,从9年的菌血症病例中获得的55株嗜麦芽嗜血杆菌分离株的分子流行病学和毒力基因频率。
    基于95%平均核苷酸同一性(ANI)和70%数字DNA-DNA杂交(dDDH)的阈值,我们将37个分离株分为6个已知物种,都属于Smc。在这项研究中测序的其余18个分离株被分配给6个新的基因组物种。在55个分离株中,我们确定了44种不同的序列类型(ST),包括22个已知的和22个新的等位基因组合。Smc对甲氧苄啶-磺胺甲恶唑(TMP/SMX)的耐药率为3.6%,在这些分离物中检测到sul1和一类整合子整合酶基因(intI)。所有Smc分离株都对米诺环素敏感。此外,所有Smc菌株都带有mota,pilu,smf-1和Stmpr2基因。同源物种1(100%,n=9),嗜麦芽窄食单胞菌(84.21%,n=19)和窄食单胞菌(71.43%,n=7)表明afaD基因的百分比较高,这也与较高的分离率有关。除了mota,pilu,smf-1和Stmpr2基因,所有嗜麦芽窄食链球菌菌株(100%)都含有entA,gspD,卡塔,和stmPr1基因,虽然所有基因物种1菌株(100%)都含有afaD,entA,gspD,和KatA基因.
    我们的研究强调了来自菌血症患者的Smc分离株的遗传多样性,揭示了22种新颖的ST类型,58个新等位基因和6个新基因组。研究发现嗜麦芽窄食链球菌和巴氏链球菌携带更多的毒力因子,强调准确菌株识别的重要性。对于对TMP/SMX耐药的患者,米诺环素是一种有前途的替代抗生素。
    UNASSIGNED: The Stenotrophomonas maltophilia complex (Smc) has emerged as a significant nosocomial pathogen contributing to increased mortality rates, particularly in case of bloodstream infections.
    UNASSIGNED: This study employed whole-genome sequencing (WGS) to assess the genetic diversity, antimicrobial resistance profiles, molecular epidemiology and frequencies of virulence genes among 55 S. maltophilia isolates obtained from bacteremic cases over a 9-year period.
    UNASSIGNED: Based on the threshold of 95% average nucleotide identity (ANI) and 70% digital DNA-DNA hybridization (dDDH) for genospecies delineation, we classified 37 isolates into 6 known species, all belonging to the Smc. The remaining 18 isolates sequenced in this study were assigned to 6 new genomospecies. Among the 55 isolates, we identified 44 different sequence types (STs), comprising 22 known and 22 novel allele combinations. The resistance rate of Smc against trimethoprim-sulfamethoxazole (TMP/SMX) was found to be 3.6%, with the sul1 and class one integron integrase genes (intI) detected in these isolates. All Smc isolates were susceptible to minocycline. Furthermore, all Smc strains harbored the motA, pilU, smf-1 and Stmpr2 genes. Genomospecies 1 (100%, n = 9), Stenotrophomonas maltophilia (84.21%, n = 19) and Stenotrophomonas sepilia (71.43%, n = 7) demonstrated a higher percentage of the afaD gene, which was also associated with a higher separation rate. In addition to motA, pilU, smf-1, and Stmpr2 genes, all S. maltophilia strains (100%) contained entA, gspD, KatA, and stmPr1 genes, while all genomospecies 1 strains (100%) contained afaD, entA, gspD, and KatA genes.
    UNASSIGNED: Our study highlights the genetic diversity among Smc isolates from patients with bacteremia, revealing 22 novel ST types, 58 new alleles and 6 new genomospecies. S. maltophilia and S. pavanii were found to carry more virulence factors, emphasizing the importance of accurate strain identification. Minocycline emerged as a promising alternative antibiotic for patients who were resistant to TMP/SMX.
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