Imipenem

亚胺培南
  • 文章类型: Case Reports
    玫瑰单胞菌属最初于1993年被描述为“粉红色的球形。\"它是一种非发酵,有氧,和革兰氏阴性菌.这个属已经在不同的环境生态位被发现,从水和土壤到空气和植物。尽管它在自然界中普遍存在,人类感染源于Roseomonas物种仍然是罕见的。还已知该生物体对标准抗生素具有抗性。我们介绍了一例85岁的吉拉迪玫瑰单胞菌(RG)菌血症妇女,她是辅助生活设施的居民。医疗保健提供者应该在缓慢发展的革兰氏阴性感染中考虑这种细菌,可能选择广谱抗生素作为初始治疗。
    Roseomonas genus was initially described in 1993 as a \"pink coccoid.\" It is a non-fermentative, aerobic, and gram-negative bacteria. This genus has been uncovered in diverse environmental niches, ranging from water and soil to air and plants. Despite its prevalence in the natural world, human infections stemming from Roseomonas species remain a rare occurrence. This organism is also known to be resistant to standard antibiotics. We present a case of an 85-year-old woman with Roseomonas gilardii (RG) bacteremia who is a resident at an assisted living facility. Healthcare providers should consider this bacterium in slow-developing gram-negative infections, potentially opting for broad-spectrum antibiotics as an initial treatment.
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  • 文章类型: Journal Article
    肺功能和免疫力受损的个体容易发生慢性脓肿分枝杆菌感染。目前的治疗建议通常涉及使用一种β-内酰胺抗生素与非β-内酰胺抗生素的组合。然而,最近的案例研究(B.贝肯,K.M.Dousa,J.L.约翰逊,S.M.荷兰,和R.A.Bonomo,抗微生物剂Chemother68:e00319-24,2024,https://doi.org/10.1128/aac.00319-24)证明了同时使用两种β-内酰胺类抗生素成功治疗儿童慢性脓肿分枝杆菌肺病。这篇评论回顾了关于双β-内酰胺治疗脓肿分枝杆菌感染的新证据和悬而未决的问题。
    Individuals with compromised lung function and immunity are susceptible to developing chronic Mycobacterium abscessus infection. Current treatment recommendations typically involve using one β-lactam antibiotic in combination with non-β-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024, https://doi.org/10.1128/aac.00319-24) demonstrated successful treatment of chronic M. abscessus lung disease in a child using two β-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual β-lactam therapy for M. abscessus infections.
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  • 文章类型: Journal Article
    脓毒症是由病原微生物入侵惹起的全身性炎症反响综合征。尽管诊断和技术取得了重大进展,发病率和死亡率仍然很高。中性粒细胞胞外诱捕网(NETs)水平与脓毒症的进展和预后密切相关。提示NET形成的调控是脓毒症治疗的新策略。由于其多效效应,阿托伐他汀,一种临床降脂药,影响脓毒症相关炎症和免疫反应的各个方面。与临床实践紧密结合,我们将其与亚胺培南联合用于治疗脓毒症。在这项研究中,我们使用盲肠结扎和穿刺诱导的肺损伤小鼠模型,并采用包括蛋白质印迹在内的技术,免疫荧光,和酶联免疫吸附试验来测量NETs水平和其他与脓毒症相关的肺损伤指标。我们的发现表明阿托伐他汀有效地抑制了NETs的形成。当与亚胺培南结合时,它显著减轻了肺损伤,减少全身性炎症,提高了脓毒症小鼠的7天存活率。此外,我们探讨了阿托伐他汀对体外NET形成的抑制机制,通过ERK/NOX2途径揭示其潜在作用。因此,阿托伐他汀是一种潜在的免疫调节药物,可为临床脓毒症患者提供新的治疗策略.
    Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.
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  • 文章类型: English Abstract
    铜绿假单胞菌是一种非发酵革兰阴性杆菌。许多毒力因子在铜绿假单胞菌的发病机制中起作用。这项研究的目的是通过基质辅助激光解吸/电离飞行时间质谱(MALDI-TOFMS)方法早期检测ST111,ST175,ST235,ST253,ST395,这些克隆被命名为高风险克隆,由于铜绿假单胞菌分离物中的多药耐药性而具有增加的流行潜力(MALDI-TOFMS)方法,并评估高风险分离物与存在之间的关系。对于毒力基因的检测,用于toxA的单重聚合酶链反应(PCR)和用于algD的多重PCR,plcN,LasB,plcH在铜绿假单胞菌分离株中进行。在碳青霉烯酶基因的检测中,用于BlaKPC的两个单独的多路复用PCR,blaNDM,BlaVIM,blaOXA-48和blaIMP,blaSPM,blaSIM,BlaGIM,blages.通过使用VITEK®-MS(bioMérieux,法国)系统。铜绿假单胞菌分离株主要来自重症监护病房(45%)和呼吸道样本(46%)。发现分离株最敏感的抗生素是阿米卡星,而哌拉西林的耐药性最高。在PCR结果中,toxa,LasB,plcH,plcN和algD检测为89%,99%,98%,100%,100%,分别。当使用MALDI-TOFMS评估属于高风险克隆的特征峰的存在时,检测到ST253(7%)和ST175(2%)。在我们的研究中未检测到对ST235和ST395克隆特异的峰。在两个分离物中检测到blaVIM,在两个分离物中检测到blaGES-5碳青霉烯酶。在高风险克隆和其他菌株中均检测到高比率的毒力因子,并且在高风险克隆和毒力因子之间没有发现显着关系。及早发现高危克隆,确定抗菌素耐药机制将有助于制定战略治疗方案并防止其在全球范围内传播。
    Pseudomonas aeruginosa is a non-fermentative gram-negative bacillus. Many virulence factors play a role in the pathogenesis of P.aeruginosa. The aim of this study was to early detection of ST111, ST175, ST235, ST253, ST395 which are named high-risk clones with increased epidemic potential due to multidrug resistance in P.aeruginosa isolates by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method and to evaluate the relationship between high-risk clones and the presence of P.aeruginosa virulence factors and carbapenemase production genes.P.aeruginosa isolates (n= 100) found to be resistant to at least imipenem or meropenem antibiotics isolated from the various clinical samples in the medical microbiology laboratory between 01.01.2021 and 07.06.2022 were included in the study. For the detection of virulence genes uniplex polymerase chain reaction (PCR) for toxA and multiplex PCR for algD, plcN, lasB, plcH were performed in P.aeruginosa isolates. In the detection of carbapenemase genes, two separate multiplex PCRs used for blaKPC , blaNDM , blaVIM , blaOXA-48 and for blaIMP , blaSPM , blaSIM , blaGIM , blaGES . Investigation of the peaks specific to high-risk clones was performed by using VITEK®-MS (bioMérieux, France) system. P.aeruginosa isolates were mostly isolated from intensive care units (45%) and respiratory tract samples (46%). The antibiotic to which the isolates were found to be most susceptible was amikacin, while highest resistance was detected for piperacillin. In PCR results, toxA, lasB, plcH, plcN and algD were detected as 89%, 99%, 98%, 100%, 100%, respectively. When the presence of characteristic peaks belonging to high-risk clones was evaluated with MALDI-TOF MS, ST253 (7%) and ST175 (2%) were detected. The peaks specific to ST235 and ST395 clones were not detected in our study. blaVIM was detected in two isolates and blaGES-5 carbapenemase was detected in two isolates. Virulence factors were detected at high rates in both high-risk clones and other strains and no significant relationship was found between high-risk clones and virulence factors. Early detection of high-risk clones, identification of antimicrobial resistance mechanisms will help to develop strategic treatment options and prevent their worldwide spread.
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  • 文章类型: Case Reports
    背景:耐碳青霉烯肺炎克雷伯菌(CRKP)感染是一个主要的公共卫生问题,需要施用多粘菌素E(粘菌素)作为最后一线抗生素。同时,与粘菌素耐药肺炎克雷伯菌感染相关的死亡率正在严重增加.另一方面,碳青霉烯类抗生素在促进肺炎克雷伯菌粘菌素耐药性中的重要性尚不清楚。
    方法:我们报告一例肺炎克雷伯菌相关化脓性肝脓肿,其中易感肺炎克雷伯菌在亚胺培南治疗期间转化为碳青霉烯和粘菌素耐药的肺炎克雷伯菌。化脓性肝脓肿的病例是一名50岁的患有糖尿病和肝移植的男子,他被送往设拉子的阿布阿里新浪医院。分离并鉴定了负责社区获得性化脓性肝脓肿的肺炎克雷伯菌。在抗菌药物敏感性试验中,除氨苄西林外,肺炎克雷伯菌分离株对所有测试的抗生素均敏感,并被鉴定为非K1/K2经典肺炎克雷伯菌(cKp)菌株。多位点序列分型(MLST)将分离株鉴定为序列类型54(ST54)。根据病人的要求,他出院继续在另一个中心治疗。两个月后,他因发烧和进行性全身症状而再次入院。在用亚胺培南治疗期间,该菌株获得了blaOXA-48,并显示出对碳青霉烯类抗生素的抗性,并被鉴定为多药耐药(MDR)菌株。通过肉汤微量稀释法进行粘菌素的最低抑制浓度(MIC)测试,该菌株对粘菌素敏感(MIC<2µg/mL)。同时,在血琼脂上,菌落具有粘性稠度并粘附于培养基(粘性粘膜粘性菌落)。定量实时PCR和生物膜形成测定显示,CRKP菌株增加了胶囊wzi基因的表达,并产生了响应亚胺培南的粘液。最后,肺炎克雷伯菌相关化脓性肝脓肿对多种抗生素耐药,包括最后一线抗生素粘菌素和替加环素,导致败血症和死亡.
    结论:根据这些信息,我们是否可以有一个理论假设,即亚胺培南是肺炎克雷伯菌对碳青霉烯类和粘菌素耐药的启动子?这需要更多的关注。
    BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, necessitating the administration of polymyxin E (colistin) as a last-line antibiotic. Meanwhile, the mortality rate associated with colistin-resistant K. pneumoniae infections is seriously increasing. On the other hand, importance of administration of carbapenems in promoting colistin resistance in K. pneumoniae is unknown.
    METHODS: We report a case of K. pneumoniae-related pyogenic liver abscess in which susceptible K. pneumoniae transformed into carbapenem- and colistin-resistant K. pneumoniae during treatment with imipenem. The case of pyogenic liver abscess was a 50-year-old man with diabetes and liver transplant who was admitted to Abu Ali Sina Hospital in Shiraz. The K. pneumoniae isolate responsible for community-acquired pyogenic liver abscess was isolated and identified. The K. pneumoniae isolate was sensitive to all tested antibiotics except ampicillin in the antimicrobial susceptibility test and was identified as a non-K1/K2 classical K. pneumoniae (cKp) strain. Multilocus sequence typing (MLST) identified the isolate as sequence type 54 (ST54). Based on the patient\'s request, he was discharged to continue treatment at another center. After two months, he was readmitted due to fever and progressive constitutional symptoms. During treatment with imipenem, the strain acquired blaOXA-48 and showed resistance to carbapenems and was identified as a multidrug resistant (MDR) strain. The minimum inhibitory concentration (MIC) test for colistin was performed by broth microdilution method and the strain was sensitive to colistin (MIC < 2 µg/mL). Meanwhile, on blood agar, the colonies had a sticky consistency and adhered to the culture medium (sticky mucoviscous colonies). Quantitative real-time PCR and biofilm formation assay revealed that the CRKP strain increased capsule wzi gene expression and produced slime in response to imipenem. Finally, K. pneumoniae-related pyogenic liver abscess with resistance to a wide range of antibiotics, including the last-line antibiotics colistin and tigecycline, led to sepsis and death.
    CONCLUSIONS: Based on this information, can we have a theoretical hypothesis that imipenem is a promoter of resistance to carbapenems and colistin in K. pneumoniae? This needs more attention.
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  • 文章类型: Journal Article
    目的:鲍氏不动杆菌是一种已知的多药耐药(MDR)的医院病原菌,尤其是碳青霉烯类药物。有几个因素有助于抵抗,包括外排泵,β-内酰胺酶,改变目标部位,和渗透性缺陷。此外,外膜蛋白(OMPs)如孔蛋白参与抗生素的通过,它们的改变可能导致抗性发展。本研究旨在探讨由于差异表达,孔蛋白和OMPs可能参与碳青霉烯耐药性的发展。
    结果:首先研究了鲍曼不动杆菌的抗生素敏感和MDR分离株的OMP表达和OMP谱的转录水平差异。抗生素敏感的分离株进一步用亚胺培南治疗,结果发现omp基因差异表达。所研究的9个基因中的6个在暴露于亚胺培南1小时时上调。它们的表达随时间逐渐降低,进一步证实了他们的OMP图谱和二维凝胶电泳。
    结论:本研究可以确定暴露于亚胺培南后差异表达的OMPs。因此,这项研究提供了特定OMPs在鲍曼不动杆菌抗生素耐药性中的作用的见解。
    OBJECTIVE: Acinetobacter baumannii is a nosocomial pathogen known to be multidrug-resistant (MDR), especially to drugs of the carbapenem class. Several factors contribute to resistance, including efflux pumps, β-lactamases, alteration of target sites, and permeability defects. In addition, outer membrane proteins (OMPs), like porins are involved in the passage of antibiotics, and their alteration could lead to resistance development. This study aimed to explore the possible involvement of porins and OMPs in developing carbapenem resistance due to differential expression.
    RESULTS: The antibiotic-susceptible and MDR isolates of A. baumannii were first studied for differences in their transcriptional levels of OMP expression and OMP profiles. The antibiotic-susceptible isolates were further treated with imipenem, and it was found that the omp genes were differentially expressed. Six of the nine genes studied were upregulated at 1 h of exposure to imipenem. Their expression gradually decreased with time, further confirmed by their OMP profile and two-dimensional gel electrophoresis.
    CONCLUSIONS: This study could identify OMPs that were differentially expressed on exposure to imipenem. Hence, this study provides insights into the role of specific OMPs in antibiotic resistance in A. baumannii.
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  • 文章类型: Journal Article
    背景:炉弧菌是一种新出现的人类病原体,与引起急性胃肠炎的河弧菌密切相关。据报道,镍弧菌感染比河弧菌更罕见,但是最近在弗氏弧菌中发现了一种多药耐药质粒。
    方法:在北京某综合医院的日常监测中,中国,我们从2018年4月至10月期间出现急性腹泻的14岁以上患者中收集了7株弗氏弧菌.进行了毒力和抗微生物药物抗性基因的基因组分析和比较,质粒和转座子岛,以及系统发育分析。使用微量肉汤稀释法研究了对19种抗生素的耐药性。基于VI型分泌系统(T6SS)表达并使用细菌杀伤测定和溶血素测定来研究毒力表型。
    结果:基于单核苷酸多态性的系统发育分析显示,与其他弧菌相比,furnissii和Fluvialis之间的关系更密切。七个V.furnissii分离株在系统发育树中处于不同的单系进化枝,提示7例胃肠炎是独立的。高抗头孢唑啉,四环素和链霉素在V.furinissii分离物中的含量分别为100.0%,57.1%和42.9%,对氨苄西林/舒巴坦和亚胺培南的中等耐药率分别为85.7%和85.7%。在测试的菌株中,VFBJ02对亚胺培南和美罗培南都有抗性,而VFBJ01、VFBJ02、VFBJ05和VFBJ07是多药耐药的。在VFBJ05的多药耐药质粒上发现了含有抗生素耐药基因的转座子岛。此类转座子岛也出现在VFBJ07中,但位于染色体上。毒力相关基因T6SS,vfh,hupo,vfp和ilpA在炉膛弧菌中普遍存在。毒力表型测定的结果表明,我们分离的V.furnissii菌株编码活化的T6SS,并在大菌落中生长,在血琼脂上具有强烈的β溶血作用。
    结论:这项研究表明,在北京夏季,与V.fenissii相关的腹泻偶尔发生,并且比预期的要普遍。中国。与河弧菌相比,炉弧菌的抗生素耐药性具有独特的特征。氟喹诺酮类药物和第三代头孢菌素,如头孢他啶和强力霉素,对治疗弧菌感染有效。为了预防和控制镍弧菌感染,需要进行持续的实验室监测,特别是抗生素抗性基因在这种病原体中的传播。
    BACKGROUND: Vibrio furnissii is an emerging human pathogen closely related to V. fluvialis that causes acute gastroenteritis. V. furnissii infection has been reported to be rarer than V. fluvialis, but a multi-drug resistance plasmid has recently been discovered in V. furnissii.
    METHODS: During daily monitoring at a general hospital in Beijing, China, seven V. furnissii strains were collected from patients aged over 14 years who presented with acute diarrhoea between April and October 2018. Genome analysis and comparison were performed for virulence and antimicrobial resistance genes, plasmids and transposon islands, together with phylogenetic analysis. Antimicrobial resistance to 19 antibiotics was investigated using the microbroth dilution method. Virulence phenotypes were investigated based on type VI secretion system (T6SS) expression and using a bacterial killing assay and a haemolysin assay.
    RESULTS: Phylogenetic analysis based on single-nucleotide polymorphisms revealed a closer relationship between V. furnissii and V. fluvialis than between other Vibrio spp. The seven V. furnissii isolates were in different monophyletic clades in the phylogenetic tree, suggesting that the seven cases of gastroenteritis were independent. High resistance to cefazolin, tetracycline and streptomycin was found in the V. furnissii isolates at respective rates of 100.0%, 57.1% and 42.9%, and intermediate resistance to ampicillin/sulbactam and imipenem was observed at respective rates of 85.7% and 85.7%. Of the tested strains, VFBJ02 was resistant to both imipenem and meropenem, while VFBJ01, VFBJ02, VFBJ05 and VFBJ07 were multi-drug resistant. Transposon islands containing antibiotic resistance genes were found on the multi-drug resistance plasmid in VFBJ05. Such transposon islands also occurred in VFBJ07 but were located on the chromosome. The virulence-related genes T6SS, vfh, hupO, vfp and ilpA were widespread in V. furnissii. The results of the virulence phenotype assays demonstrated that our isolated V. furnissii strains encoded an activated T6SS and grew in large colonies with strong beta-haemolysis on blood agar.
    CONCLUSIONS: This study showed that diarrhoea associated with V. furnissii occurred sporadically and was more common than expected in the summer in Beijing, China. The antibiotic resistance of V. furnissii has unique characteristics compared with that of V. fluvialis. Fluoroquinolones and third-generation cephalosporins, such as ceftazidime and doxycycline, were effective at treating V. furnissii infection. Continua laboratory-based surveillance is needed for the prevention and control of V. furnissii infection, especially the dissemination of the antibiotic resistance genes in this pathogen.
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  • 文章类型: Journal Article
    背景:嗜麦芽窄食单胞菌和相关物种引起的感染在世界范围内正在增加。不幸的是,治疗选择有限,而抗菌素耐药性正在增加。
    方法:我们纳入了通过VITEK2Compact鉴定为嗜麦芽嗜血杆菌的临床分离株。头孢他啶/阿维巴坦,美罗培南/vaborbactam,亚胺培南/雷巴坦,cefiderocol,喹诺酮类药物,和四环素家族成员通过肉汤微量稀释法进行评估,并与一线治疗药物进行比较。报告了所有抗生素的最小抑制浓度(MIC)。我们对头孢地洛耐药菌株(CRS)的全基因组进行了测序,并注释了与头孢地洛耐药(GACR)相关的基因。使用16S标记进行了推定的系统发育鉴定。
    结果:评估了一百一十种临床菌株,磺胺甲恶唑和甲氧苄啶,左氧氟沙星和米诺环素的敏感性为99.01%,分别为95.04%和100%。头孢他啶是所有样品中抗性百分比最高的抗生素(77.22%)。5株对头孢地洛耐药,MIC值≥2μg/mL(4.95%)。β-内酰胺酶抑制剂美罗培南/伐巴坦和亚胺培南/雷巴坦,未能抑制嗜麦芽嗜血杆菌,保留MIC50和MIC90≥64μg/mL。头孢他啶/阿维巴坦恢复了头孢他啶的活性,降低了MIC范围。替加环素的MIC范围最低,MIC50和MIC90。基于16SrRNA的系统发育可以鉴定出头孢地醇抗性菌株,因为推定的物种聚集到嗜麦芽窄食单胞菌复合体(Smc)中。在这些菌株中,我们检测到GARCs,如多重耐药(MDR)外排泵,L1型β-内酰胺酶,铁转运蛋白和1型菌毛。
    结论:抗菌药物对一线治疗的耐药性较低。新型β-内酰胺酶抑制剂对嗜麦芽窄食链球菌的体外活性较差,但阿维巴坦可能是个潜在的选择.头孢地洛可以被认为是治疗多药耐药感染的潜在新选择。四环素在所有评估的抗生素中具有最佳的体外活性。
    BACKGROUND: Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing.
    METHODS: We included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed.
    RESULTS: One hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 μg/mL (4.95%). The β-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 μg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type β-lactamases, iron transporters and type-1 fimbriae.
    CONCLUSIONS: Antimicrobial resistance to first-line treatment is low. The in vitro activity of new β-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.
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  • 文章类型: Journal Article
    本研究旨在通过分子对接和实时聚合酶链反应(PCR)研究双组分系统BaeSR在耐碳青霉烯类鲍曼不动杆菌(CRAB)耐药机制中的作用。将鲍曼不动杆菌的双组分体系BaeSR与亚胺培南进行分子对接,美罗培南,和左氧氟沙星.采用抗菌试验和荧光定量PCR方法探讨了与CRAB相关的蛋白质-配体相互作用和分子生物学耐药机制。对鲍曼不动杆菌中双组分体系的分析显示,亚胺培南在BaeS中表现出最高的对接能,为-5.81kcal/mol,美罗培南的对接能量为-4.92kcal/mol。对于BaeR来说,亚胺培南的最大对接能量为-4.28kcal/mol,与美罗培南的-4.60kcal/mol相比。BaeS-左氧氟沙星和BaeR-左氧氟沙星的最高结合能分别为-3.60和-3.65kcal/mol,分别。所有耐亚胺培南菌株的最低抑菌浓度(MIC)值为16µg/mL,而左氧氟沙星耐药菌株的MIC值为8µg/mL。时间灭菌曲线显示,在8µg/mL亚胺培南的作用下,细菌菌落数在2小时显着减少,表明抗菌作用。相比之下,左氧氟沙星没有任何抗菌活性。荧光定量PCR结果显示,CRAB组中baeS和baeR基因的相对表达水平显著升高,比CSAB组高2倍和1.5倍,分别,具有统计学上的显著差异。本研究中的分子对接发现BaeSR与碳青霉烯类抗生素(亚胺培南,美罗培南)与左氧氟沙星相比具有更强的亲和力和稳定性。此外,双组分系统基因在耐碳青霉烯鲍曼不动杆菌中的过表达增强了其对碳青霉烯的抗性,为鲍曼不动杆菌引起的呼吸道感染中的碳青霉烯耐药性提供理论和实践见解。
    This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81 kcal/mol, while the docking energy for meropenem was - 4.92 kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28 kcal/mol, compared with - 4.60 kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65 kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16 µg/mL, whereas levofloxacin-resistant strains had MIC values of 8 µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2 h under the action of 8 µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii.
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  • 文章类型: Meta-Analysis
    背景:本系统综述旨在确定尼泊尔尿液样本中产生超广谱β-内酰胺酶的大肠杆菌(ESBL-EC)的抗菌耐药性模式。
    方法:进行了系统文献综述,以查找2012年1月至2022年12月期间发表的所有报告ESBL-EC的尿液样本中的文章。进行Egger加权回归分析以评估发表偏倚。由于研究之间的显着异质性,使用随机效应模型来计算合并的患病率和相应的95%置信区间。使用Pearson相关系数确定了多药耐药性与大肠杆菌中ESBL产生之间的相关性强度。使用R语言4.2.2分析数据。软件。
    结果:发现尿液样本中大肠杆菌的合并患病率为14%(95%CI,11-18),而ESBL大肠杆菌和MDR大肠杆菌的总体合并患病率分别为30%(95%CI,20-42)和70%(95%CI,38-90)。在大肠杆菌分离株中,ESBL生产与MDR之间存在0.99(95%CI,0.89-1.0)的强正相关。亚胺培南是对抗ESBL-E的首选药物。尿液标本中的大肠杆菌。
    结论:我们的分析显示,尼泊尔的ESBL-EC和MDR-EC总体负担相当高。同样,该研究还推断尿液样本中ESBL-EC的抗生素耐药模式有增加的趋势.
    BACKGROUND: This systematic review aimed to determine the antimicrobial resistance pattern of the extended-spectrum β-lactamases producing Escherichia coli (ESBL-EC) in urine samples in Nepal.
    METHODS: Systematic literature review was conducted to locate all articles reporting ESBL-EC in urine samples published between January 2012 to December 2022. The Egger\'s weighted regression analysis was done to assess the publication bias. A random-effects model was used to calculate the pooled prevalence and corresponding 95% confidence interval due to significant between-study heterogeneity. The strength of correlation between multidrug resistance and ESBL production in E.coli strains was determined using Pearson\'s correlation coefficient. The data were analyzed using R-language 4.2.2. software.
    RESULTS: The combined prevalence of E.coli in urine samples was found to be 14 % (95% CI, 11-18), while the overall pooled prevalence of ESBL E.coli and MDR E.coli were 30% (95% CI, 20-42) and 70% (95% CI, 38-90) respectively. A strong positive correlation of 0.99 (95% CI, 0.89-1.0) was found between ESBL production and MDR among E.coli isolates. Imipenem was the drug of choice against ESBL-E.coli in urine specimens.
    CONCLUSIONS: Our analyses showed the overall ESBL-EC and MDR-EC burden in Nepal is considerably high. Likewise, the study also infers an increasing trend of antibiotic resistance pattern of ESBL-EC in urine samples.
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