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The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers
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作者 Zhuoren Ling Alistair James Macdonald Farley +17 位作者 Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher Joseph Schofield Timothy Walsh 《Engineering》 SCIE EI CAS CSCD 2024年第7期124-132,共9页
This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spect... This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method.The frequency of resistance(FoR)to MEM combined with InC58 was investigated.Mutants were sequenced and tested for cross resistance,fitness,and the stability of the resistance phenotype.Compared with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(P.aeruginosa)and OXA-23-carrying Acinetobacter baumannii(A.baumannii).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,respectively.The mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance. 展开更多
关键词 CARBAPENEMASE metallo/serine-b-lactamase inhibitor Avibactam MEROPENEM Antimicrobial resistance
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Evaluation of Disk Potentiation Test (DPT) and Double Disk Synergy Test (DDST) for The Detection of Metallo-β-Lactamases (MBLs) in Clinical Isolates of Bangladesh
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作者 Sumon Kumar Das Afzal Sheikh +4 位作者 Nikhat Ara Suma Mita Biswas Abhinandan Chowdhury Fatimah Az Zahra Chaman Ara Keya 《Advances in Infectious Diseases》 2023年第4期609-626,共18页
Objective: Increasing the emergence of Metallo-β-lactamase (MBL) producing gram-negative bacteria and their dexterous horizontal transmission demands rapid and accurate detection. This study was conducted to determin... Objective: Increasing the emergence of Metallo-β-lactamase (MBL) producing gram-negative bacteria and their dexterous horizontal transmission demands rapid and accurate detection. This study was conducted to determine a suitable method to promptly detect MBL-producing gram-negative bacteria. Methods: A total of 103 gram-negative bacteria were identified from various clinical samples at a tertiary care hospital in Dhaka city. MBL producers were detected by two phenotypic methods, the Disk Potentiation Test (DPT) and the Double Disk Synergy Test (DDST) based on β-lactam chelator combinations where EDTA/SMA has been used as an inhibitor and Imipenem, Ceftazidime as substrates. Results: 103 isolates which were identified as Escherichia coli spp, Klebsiella spp, Pseudomonas spp, Acinetobacter spp, Proteus spp, Providencia spp were found to be multidrug-resistant in antibiogram test. Isolates showed complete resistance (100%) to Imipenem, Meropenem, and Amoxiclav. The highest carbapenem-resistant etiological agents were Acinetobacter spp 40 (38.8%) followed by Pseudomonas spp 27 (26.2%), Klebsiella spp 26 (25.2%), Escherichia coli 8 (7.8%), Proteus spp 1 (1%) and Providencia spp 1 (1%). DPT method detected significantly (p = 0.000009) a higher number of MBL-producers (Imipenem with 0.5 M EDTA n = 61, 59.2% & Ceftazidime with 0.5 M EDTA n = 56, 54.4%) compared to the DDST method (Imipenem -0.5 M EDTA n = 43, 41.7%, Imipenem – SMA n = 38, 36.9% & Ceftazidime -0.5 M EDTA n = 15, 14.6%). Conclusion: Pieces of evidence suggest that DPT is a more sensitive method than DDST and could be recommended for identifying MBL-producing bacteria in Bangladeshi hospitals for the proper management of patients, to reduce time constraints and treatment costs. 展开更多
关键词 Disk Potentiation Test (DPT) Double Disk Synergy Test (DDST) metallo-β-Lactamase (MBL) Sodium Mercaptoacetate (SMA) and Ethylenediaminetetraacetic Acid (EDTA)
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小鼠肝脏金属硫蛋白Metallothioneins的分离纯化与鉴定 被引量:10
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作者 茹炳根 潘爱华 +1 位作者 王正新 张龙翔 《生物化学杂志》 CSCD 1991年第3期285-290,共6页
由健康小鼠通过皮下注射一定量的氯化镉,取肝脏匀浆,离心,经SephadexG-50和DEAE-Sephadex A-50柱层析分离,即可获得MT-Ⅰ和MT-Ⅱ两种金属硫蛋白。经鉴定:两个分子各含18个巯基,结合4个Cd原子和3个Zn原子,无金属蛋白质Thionein的分子量约... 由健康小鼠通过皮下注射一定量的氯化镉,取肝脏匀浆,离心,经SephadexG-50和DEAE-Sephadex A-50柱层析分离,即可获得MT-Ⅰ和MT-Ⅱ两种金属硫蛋白。经鉴定:两个分子各含18个巯基,结合4个Cd原子和3个Zn原子,无金属蛋白质Thionein的分子量约为6kD,半胱氨酸含量约占氨基酸总量的28%,所提取到的MT-Ⅰ和MT-Ⅱ经氨基酸组成,HPLC和PAGE分析皆证明为高度均一的,且与有关文献报道基本相符。其中MT-Ⅱ已获得晶体。 展开更多
关键词 肝脏 金属硫蛋白
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Identification and Distribution of the Clinical Isolates of Imipenem-resistant Pseudomonas aeruginosa Carrying Metallo-β-lactamase and/or Class 1 Integron Genes 被引量:6
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作者 程曦 王频佳 +5 位作者 王跃 张红 陶传敏 杨维青 刘梅 贾文祥 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2008年第3期235-238,共4页
To investigate the distribution of the genes of two major metallo-β-1actamases (MBL;i.e.,IMP and VIM) and class 1 integrons (intI) in the clinical imipenem-resistant Pseudomonas aeruginosa, a total of 65 isolates... To investigate the distribution of the genes of two major metallo-β-1actamases (MBL;i.e.,IMP and VIM) and class 1 integrons (intI) in the clinical imipenem-resistant Pseudomonas aeruginosa, a total of 65 isolates, from a university hospital in Sichuan between December 2004 and April 2005 were screened for MBL genes by PCR using primers specific for blaIMP-1, blaVIM and blaVIM-2 genes. The MBL-positive isolates were further assessed for class 1 integrons by PCRusing specific primers. The nucleotide sequences of several PCR products were also determined. The results revealed that the blaVIM gene was found in 81.5% (53/65) of all isolates, blaVIM-2 gene was found in only 1 isolate and the intl gene was observed in 45.3% (24/53) of blaVIM-positive isolates. One isolate carried simultaneously both blaIMP-1 and intl genes, and to the best of our knowledge this is the first report of such isolate in southwest China. These observations highlight that the genes for VIM β-1actamase and class 1 integrons were predominantly present among the imipenem-resistant P. aeruginosa tested, confirming the current widespread threat of imipenem-resistant, integron-borne P.aeruginosa. 展开更多
关键词 Pseudomonas aeruginosa metallo-β-1actamases INTEGRON
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Numerical Simulation and Technological Parameter Optimization for Quenching Process of a Gas Turbine Compressor Disk Based on Metallo-Thermo-Mechanics 被引量:1
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作者 Cheng LUE Liwen ZHANG +2 位作者 Qing'an TAI Quying ZHENG Zhaokun WANG 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2006年第6期860-864,共5页
Thermal, mechanical and microstructural phenomena are involved in the process of steel quenching. Based on the coupled metallo-thermo-mechanics theory, a calculation model has been developed in this study to simulate ... Thermal, mechanical and microstructural phenomena are involved in the process of steel quenching. Based on the coupled metallo-thermo-mechanics theory, a calculation model has been developed in this study to simulate the quenching process of a gas turbine compressor disk by finite element method. The thermal physical and mechanical properties were treated as a functions of temperature. Moreover, a series of subroutines were developed on the MARC software platform. Consequently, simulated results on temperature, internal stress and distortion during the quenching were illustrated. With the aid of the simulated results, an optimum quenching scheme was proposed. The quenching process simulated in this study appears to be a promising tool in design of heat-treatment processing parameters for gas turbine compressor disks. 展开更多
关键词 Quenching stress DISTORTION Finite element method metallo-thermo-mechanics
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Metallo-β-lactamase producing nonfermentative gram-negative bacteria:An increasing clinical threat among hospitalized patients
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作者 Varsha Gupta Shailpreet Sidhu Jagdish Chander 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2012年第9期718-721,共4页
Objective:To detect and evaluate the various methods for metallo-β-lactamases(MBL) production in Pseudomonas aeruginosa(P.aeruginosa) and Acinetobacter species.Methods:A total of 109 P.aeruginosa and 85 Acinetobacter... Objective:To detect and evaluate the various methods for metallo-β-lactamases(MBL) production in Pseudomonas aeruginosa(P.aeruginosa) and Acinetobacter species.Methods:A total of 109 P.aeruginosa and 85 Acinetobacter species were screened for imipenem resistance by Kirby- Bauer disc diffusion methods.Detection of MBL production was(lone by imipenem-EDTA combined disc test,double disc synerygy test(DDST) and imipenem-EDTA MBL E test.Results: A total of 63(57.8%) strains of P.aeruginosa and 46(54.1%) strains of Acinetobacter spp.were found to be resistant to imipenem.Of the 63 imipenem resistant P.aeruginosa tested for MBL production.44(69.89;) were found to be positive and among 46 imipenem resistant Acinetobacter. 19(41.3%) were shown to be the MBL producers.Conclusions:Imipenem-EDTA combined disc test and MBL E test are equally effective for MBL detection in both P.aeruginosa and Acinetobacter spp.,but given the cost-constraints,combined disc can be used as a convenient screening method in the clinical microbiology laboratory. 展开更多
关键词 Carbapenem-imipenem metallo-β-lactamases Non fermentative GRAM-NEGATIVE BACILLI
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Prevalence and Antimicrobial Susceptibility Profile of Metallo-<i>β</i>-Lactamase Producing <i>Pseudomonas aeruginosa</i>Isolates at Kenyatta National Hospital
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作者 Jane Njeri Karuitha Odera Susan Akinyi +1 位作者 Maina Anne Njeri Mureithi Marianne 《Advances in Microbiology》 2018年第11期885-893,共9页
Pseudomonas aeruginosa is a major cause of nosocomial infections with high mortality rates. The organism is highly resistant to most classes of drugs used and can develop resistance during treatment. One of the resist... Pseudomonas aeruginosa is a major cause of nosocomial infections with high mortality rates. The organism is highly resistant to most classes of drugs used and can develop resistance during treatment. One of the resistance mechanisms of P. aeruginosais is Metallo-β-Lactamase (MBL) production. MBL producing P. aeruginosa is a major health concern given it’s resistance to almost all available drugs. The prevalence of this resistant strain is unknown since there is no standardized method for testing MBL production. This was a laboratory based cross-sectional prospective study that was carried out from September 2015 to March 2016 at Kenyatta National Hospital. Ninety-nine isolates of P. aeruginosa were collected during the period and tested for antimicrobial susceptibility and isolates found to be resistant to imipenem tested for MBL production. The results indicated high resistance of P. aeruginosa to commonly used drugs. Of the isolates tested 69.7% were resistant to piperacillin, 63.6% were resistant to aztreonam, 58.6% were resistant to levofloxacin, 55.6% were resistant to cefipime, 65.7% were resistant to ceftazidime, 68.7% were resistant to ticarcillin-clavulanate, 72.2% were resistant to meropenem, 64.9% were resistance to imipenem while 86.4% of urine isolates were resistant to ofloxacin. Of the isolates resistant to imipenem 87.3% were found to be MBL producers. In conclusion, P. aeruginosais highly resistant to the drugs currently is used for treatment and resistance to carbapenems is largely due to MBL production. 展开更多
关键词 Pseudomonas aeruginosa metallo-Β-LACTAMASE Antimicrobial Resistance Kenyatta NATIONAL HOSPITAL
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Phenotypic and Genotypic Characterization of Metallo-Beta-Lactamase and Extended-Spectrum Beta-Lactamase among Enterobacteria Isolated at National Public Health Laboratory of Brazzaville
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作者 Nicole Prisca Makaya Dangui Nieko Cyr Jonas Morabandza +4 位作者 Moїse Doria Kaya-Ongoto Duchel Jeanedvi Kinouani Kinavouidi Haman Judel Mikia Fabien Kangoula-Dia-Kikouidi-Kia-Louzala Fabien Roch Niama 《Advances in Microbiology》 2022年第6期363-377,共15页
The improper use of antimicrobials against infectious diseases has allowed microorganisms to develop defense mechanisms that give them insensitivity to these agents. All bacteria are concerned by this phenomenon. This... The improper use of antimicrobials against infectious diseases has allowed microorganisms to develop defense mechanisms that give them insensitivity to these agents. All bacteria are concerned by this phenomenon. This work aimed to assess prevalence of beta-lactamase produced by enterobacterial isolates. Then, disc diffusion, double disc synergy test (DDST) and combined disc test (CDT) were respectively used for antimicrobial resistance, detection of Extended-Spectrum Beta-Lactamases (ESBL) and Metallo-Beta-Lactamases (MBL). bla genes were detected by PCR. A total of 132 enterobacterial strains were studied. Resistance to antibiotic families was observed with a greater frequency than 50%. Gentamicin was the least active beta-lactam antibiotic, with a resistance rate of 88%. 40.9% of strains show an ESBL phenotype and 16.6% were MBL. An overall prevalence of 74% (40/54) and respectively rates of 29.6%, 27.7% and 16.7% for blaSHV, blaCTX and blaTEM genes were observed. SHV, CTX, CTX/SHV/TEM, CTX/TEM, SHV/TEM and CTX/SHV were different ESBL genotypes observed. ESBL-producing enterobacteria isolation worried about the future of antimicrobial therapy in the Republic of Congo. This is a public health problem that requires careful monitoring and implementation of a policy of rational antibiotics use. 展开更多
关键词 ENTEROBACTERIA Antibiotic Resistance Extended-Spectrum Beta-Lactamases metallo-Beta-Lactamases bla Genes
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Interaction between Metal in Metallo Enzyme and Small Biological Molecules 被引量:1
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作者 Hu Jie-Han Shu Zan-Yong +1 位作者 Tao Li-Mei Cheng Guo-Bao(Dalian Institute of Chemical Physics, Academia Sinica, Dalian 116023) 《Chinese Journal of Structural Chemistry》 SCIE CAS CSCD 1996年第1期24-30,共7页
In this work, the existence of interaction between metal in metallo enzyme and small biological molecules such as amino acid in aqueous solution is confirmed for the first time by the experimental data of ESR, NMR,UV-... In this work, the existence of interaction between metal in metallo enzyme and small biological molecules such as amino acid in aqueous solution is confirmed for the first time by the experimental data of ESR, NMR,UV-VIS and enzyme activity. This kind of interaction can affect the enzyme catalytic activity. 展开更多
关键词 biological molecules metallo enzyme INTERACTION
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Lead in K-Feldspar and Its Relations to Pb Metallogenesis
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作者 张乾 刘志浩 +2 位作者 裘愉卓 高计元 王一先 《Chinese Journal Of Geochemistry》 EI CAS 2003年第2期107-115,共9页
In intermediate-acid magmatic rocks,alkaline magmatic rocks,gneisses and migmatitic rocks K-feldspar is a rook-forming rock in which the contents of Pb are highest,just 2-10 times those of the whole rock,3-16 times th... In intermediate-acid magmatic rocks,alkaline magmatic rocks,gneisses and migmatitic rocks K-feldspar is a rook-forming rock in which the contents of Pb are highest,just 2-10 times those of the whole rock,3-16 times those of mica minerals and 6-32 times those of quartz.The lowest contents of K-feldspar are recognized in Early Proterozoic and Achaean rocks,with Pb in the K-feldspar accounting for less than 10% of that in the whole rock;in post-Middle Proterozoic alkaline magmatic rocks,K-feldspar-rich granites and metamorphic rocks the contents of K-feldspar tend to increase,with the proportion of Pb over that in the whole rock being obviously increased.In the alkaline rocks in which K-feldspar accounts for 50%-70%of the total in the whole rock,the contents of Pb in K-feldspar account approximately for 70%-95% of the total lead in the whole rock.Being accessible to hydrothermal alteration in the late periods,K-feldspar was conversed to sericite,calcite,quartz,etc.In the process of such conversion the lead would be leached out and then find its way into fluid phase.This kind of trans-formation can provide sufficent ore-forming material for later Pb metallogenesis. 展开更多
关键词 岩石 铅矿床 钾长石 地球化学 金属成矿作用 流体相
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Biosynthesis of trialkyl-substituted aromatic polyketide NFAT-133 involves unusual P450 monooxygenase-mediating aromatization and a putative metallo-beta-lactamase fold hydrolase
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作者 Ming Yang Wanlu Li +6 位作者 Lin Zhou Xiao Lin Wenyu Zhang Yaoyao Shen Hai Deng Hou-wen Lin Yongjun Zhou 《Synthetic and Systems Biotechnology》 SCIE CSCD 2023年第3期349-356,共8页
The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123(1),veramycin A(2),NFAT-133(3)and benwamycin I(4),which ... The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123(1),veramycin A(2),NFAT-133(3)and benwamycin I(4),which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities.Though the biosynthetic pathway of 1-3 was reported as a type I polyketide synthase(PKS),the PKS assembly line was interpreted inconsistently,and it remains a mystery how the compound 3 was generated.Herein,the PKS assembly logic of 1-4 was revised by site-mutagenetic analysis of the PKS dehydratase domains.Based on gene deletion and complementation,the putative P450 monooxygenase nftE1 and metallo-beta-lactamase(MBL)fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1-4.The absence of nftE1 led to abolishment of 1-4 and accumulation of new products(5-8).Structural elucidation reveals 5-8 as the non-aromatic analogs of 1,suggesting the NftE1-catalyzed aromatic core formation.Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected.As a rare MBL-fold hydrolase from type I PKSs,NftF1 potentially generates the compound 3 through two strategies:catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase. 展开更多
关键词 Thioesterase metallo hydrolase metallo-BETA-LACTAMASE Aromatic polyketide Polyketide synthase P450 monooxygenase
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IMB-XH1 identified as a novel inhibitor of New Delhi metallo-β-lactamase-1 被引量:2
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作者 韩江雪 肖春玲 +9 位作者 甘茂罗 李兴华 王颖 郑佳音 李东升 刘琛楠 关艳 蒙建州 黄树超 刘忆霜 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2019年第4期238-246,共9页
The problem of drug resistance of Gram-negative bacteria has become increasingly serious and has aroused widespread public concern.The "super bacteria" producing New Delhi metallo-beta-lactamase(NDM-1) are r... The problem of drug resistance of Gram-negative bacteria has become increasingly serious and has aroused widespread public concern.The "super bacteria" producing New Delhi metallo-beta-lactamase(NDM-1) are resistant to almost all β-lactam antibiotics.However, clinically existing β-lactamase inhibitors are ineffective against metallo-β-lactamases(MBLs) including NDM-1.Therefore, effective NDM-1 inhibitors are urgently needed.In this study, a high-throughput screening model for NDM-1 inhibitors was optimized and used to screen NDM-1 inhibitors.As a result, IMB-XH1 was screened out as a novel NDM-1 inhibitor from 52 100 compounds of different sources.The combined use of IMB-XH1 can increase the sensitivity of E.coli BL21(DE3)(pET-30 a(+)-NDM-1) to β-lactam antibiotics.Enzymatic kinetic studies indicate that IMB-XH1 is a non-competitive inhibitor of NDM-1 and also has inhibitory activity against other MBLs such as IMP-4, ImiS and L1.As a novel NDM-1 inhibitor, its activity and mechanism of action need to be further explored. 展开更多
关键词 NDM-1 metallo-β-lactamases INHIBITOR High THROUGHPUT screening BACTERIAL resistance
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Expression of gelatinases and tissue inhibitors of metallo-proteinases in the rhesus monkey(Macaca mulatta) corpus luteum
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作者 LI Qinglei, WANG Hongmei, SHAO Longjiang, YU Xiaoguang, Nl Jiang & ZHU Cheng1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China 2. Laboratory of Reproductive Endocrinology, Harbin Medical University, Harbin 150001, China 《Chinese Science Bulletin》 SCIE EI CAS 2001年第15期1292-1296,共5页
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are believed to play important roles in the formation and regression of corpus luteum (CL). This study is to investigate the expression of gelatinas... Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are believed to play important roles in the formation and regression of corpus luteum (CL). This study is to investigate the expression of gelatinases (MMP-2, -9) and TIMPs in the rhesus monkey CL in both early and late luteal phases and during the early stages of pregnancy. Ovaries were collected from regularly cycling rhesus monkey at D5 and D15 following ovulation and at D12, D18 and D26 of pregnancy. In situ hybridization revealed that in the CL MMP-2 niRNA was expressed during both formation and regression, while MMP-9 mRNA was mainly localized in the late luteal phase. Reduction of MMP-2, -9 transcripts in the CL was observed during pregnancy. MMP-2 mRNA in the CL reduced to an undetectable level at D26 of pregnancy. TIMP-1 mRNA was highly expressed in the CL in both early and late luteal phases and persisted throughout the early stages of pregnancy. Strong signal for TIMP-2 mRNA was also detected in both luteal phases, and the 展开更多
关键词 matrix metalloPROTEINASES tissue INHIBITORS of metallo-proteinases GELATINASES MACACA MULATTA CORPUS luteum.
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中耳胆脂瘤骨质破坏机制研究进展
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作者 刘雪华 张肖林 +1 位作者 李长叶 王延飞 《国际医药卫生导报》 2024年第19期3203-3207,共5页
中耳胆脂瘤是角化的鳞状上皮脱落后在中耳内形成的囊性结构,为非真性肿瘤,其临床表现与化脓性中耳炎相似,主要为耳流脓、听力下降、眩晕及耳痛等症状。严重者可以压迫周围骨质,造成破坏性骨吸收,引起一系列并发症,严重影响患者健康及预... 中耳胆脂瘤是角化的鳞状上皮脱落后在中耳内形成的囊性结构,为非真性肿瘤,其临床表现与化脓性中耳炎相似,主要为耳流脓、听力下降、眩晕及耳痛等症状。严重者可以压迫周围骨质,造成破坏性骨吸收,引起一系列并发症,严重影响患者健康及预后。近些年,基质金属蛋白酶、核因子κB受体活化因子配体/骨保护素、炎症因子、巨噬细胞和角质细胞生长因子在中耳胆脂瘤骨质破坏中的作用越来越受到人们的关注。本文对中耳胆脂瘤骨质破坏机制研究进展作一综述。 展开更多
关键词 基质金属蛋白酶 胆脂瘤 核因子ΚB受体活化因子配体 炎症 巨噬细胞 角质细胞生长因子 进展
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Characterization of multidrug-resistant and metallo-beta- lactamase-producing Pseudomonas aeruginosa isolates from a paediatric clinic in China 被引量:8
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作者 DONG Fang XU Xi-wei SONG Wen-qi LU Ping YU Sang-jie YANG Yong-hong SHEN Xu-zhuang 《Chinese Medical Journal》 SCIE CAS CSCD 2008年第17期1611-1616,共6页
Background In the present study, we characterized multidrug-resistant Pseudomonas aeruginosa (MDRP) clinical isolates from a paediatric facility and investigated the types and features of the metallo-β-lactamases ... Background In the present study, we characterized multidrug-resistant Pseudomonas aeruginosa (MDRP) clinical isolates from a paediatric facility and investigated the types and features of the metallo-β-lactamases (MBLs) produced by carbapenem-resistant strains. Methods Four hundred and ninety-eight strains of Pseudomonas aeruginosa were isolated from patients at Beijing Children's Hospital between January 2005 and December 2006. The minimal inhibition concentrations (MICs) of the strains for 13 antibiotics were measured. A combination of the E test and PCR amplification/DNA sequencing was used to define the carbapenem-resistant strains. Results We found that 24.1% (120/498) of the isolates were MDRP. The frequencies of resistance to imipenem and meropenem were 34.2% and 35.8%, respectively, and the MIC50 and MIC90values for the two antibiotics were identical at 4 pg/ml and 32 pg/ml, respectively. The detection rate for carbapenem resistance was 49.2% (59/120). Among the 59 carbapenem-resistant Pseudomonas aeruginosa strains, 39 (66.1%) were positive for the MBL genotype; 35 (89.7%) strains carried the blaiMp gene and 4 (10.3%) strains carried the blavm gene. Neither blasPM nor blaGiM was amplified from any of the 59 isolates. DNA sequencing revealed that IMP-1 was present in 35 IMP-producing isolates and VIM-2 was detected in four VIM-producing isolates. Conclusions These MDRP isolates exhibited high frequencies of resistance to carbapenems among clinical isolates from a paediatric facility in Beijing, China. The production of MBL appears to be an important mechanism for carbapenem resistance in Pseudomonas aeruginosa. 展开更多
关键词 PAEDIATRICS Pseudomonas aeruginosa carbapenem metallo-β-lactamases
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两株携带bla_(NDM)基因肠杆菌目细菌的分子流行病学特征研究
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作者 王健 李轶 +1 位作者 白振宇 崔世平 《中国合理用药探索》 CAS 2024年第6期33-39,共7页
目的:了解平顶山某医院两株携带bla_(NDM)基因肠杆菌目细菌临床分离株的分子流行病学特征,为该类病原菌的院内感染预防与控制提供理论依据。方法:收集2022年1~12月临床分离的耐碳青霉烯类肠杆菌目细菌(CRE)。先通过聚合酶链反应(PCR)筛... 目的:了解平顶山某医院两株携带bla_(NDM)基因肠杆菌目细菌临床分离株的分子流行病学特征,为该类病原菌的院内感染预防与控制提供理论依据。方法:收集2022年1~12月临床分离的耐碳青霉烯类肠杆菌目细菌(CRE)。先通过聚合酶链反应(PCR)筛选携带bla_(NDM)基因的CRE菌株,再对菌株携带的其他耐药基因[包括碳青霉烯酶、超广谱β-内酰胺酶(ESBLs)和喹诺酮类耐药相关基因]进行扩增,并测序确认,通过多位点序列分型(MLST)的方法分析相同种属菌株间的亲缘关系。结果:收集的CRE中有2株检测到携带bla_(NDM)基因,其中1株为携带bla_(NDM)-1的弗氏柠檬酸杆菌,另1株为携带bla_(NDM)-5的大肠埃希菌。这两株菌同时携带多个耐药基因,表现为多重耐药。MLST结果显示,产NDM-1型金属酶的弗氏柠檬酸杆菌为ST85型,产NDM-5型金属酶的大肠埃希菌为ST736型,均不是常见流行克隆类型。采用bla_(NDM)探针进行Southern杂交的结果显示,bla_(NDM)-1基因定位于一个~54kb的质粒上,bla_(NDM)-5基因定位于一个~104kb的质粒上,两个携带bla_(NDM)基因的质粒均不能发生接合。结论:首次在平顶山地区报道携带bla_(NDM)基因的CRE菌株;两株菌均同时携带多个耐药基因;bla_(NDM)基因均位于质粒且都与插入序列(IS)移动元件相关,建议进一步加强院感监测及防控,防止耐药菌株的传播和流行。 展开更多
关键词 耐碳青霉烯类肠杆菌目细菌 新德里金属β-内酰胺酶(NDM) 感染 流行病学 耐药基因
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New Delhi Metallo-β-Lactamase-Mediated Carbapenem Resistance: Origin, Diagnosis, Treatment and Public Health Concern 被引量:5
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作者 Wen-Juan Wei Hai-Fei Yang +1 位作者 Ying Ye Jia-Bin Li 《Chinese Medical Journal》 SCIE CAS CSCD 2015年第14期1969-1976,共8页
Objective: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-β-lactamase (NDM)-producing bacteria. Data Sources: We searched database for studies published in English. The ... Objective: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-β-lactamase (NDM)-producing bacteria. Data Sources: We searched database for studies published in English. The database of PubMed from 2007 to 2015 was used to conduct a search using the keyword term "NDM and Acinetobacter or Enterobacteriaceae or Pseudomonas aeruginosa." Study Selection: We collected data including the relevant articles on international transmission, testing methods and treatment strategies of NDM-positive bacteria. Worldwide NDM cases were reviewed based on 22 case reports. Results: The first documented case of infection caused by bacteria producing NDM- 1 occurred in India, in 2008. Since then, 13 blaNDM variants have been reported. The rise of NDM is not only due to its high rate of genetic transfer among unrelated bacterial species, but also to human factors such as travel, sanitation and food production and preparation. With limited treatment options, scientists try to improve available therapies and create new ones. Conclusions: In order to slow down the spread of these NDM-positive bacteria, a series of measures must be implemented. The creation and transmission of blaNDM are potentially global health issues, which are not issues for one country or one medical community, but for global priorities in general and for individual wound care practitioners specifically. 展开更多
关键词 BACTERIAL Carbapenem Resistance Drug Resistance New Delhi metallo-β-Lactamase
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活血通窍汤辅助治疗对动脉瘤性蛛网膜下腔出血并发脑血管痉挛临床疗效及对血清基质金属蛋白酶-9同型半胱氨酸和可溶性细胞间黏附分子-1水平的影响
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作者 宋金辉 余丹华 +1 位作者 周金丽 施婵宏 《中国药物与临床》 CAS 2024年第20期1304-1308,共5页
目的分析活血通窍汤辅助治疗对动脉瘤性蛛网膜下腔出血(SAH)并发脑血管痉挛(CVS)挛患者临床疗效及对血清基质金属蛋白酶(MMP)-9、同型半胱氨酸(Hcy)和人可溶性细胞间黏附分子-1(sICAM-1)的影响。方法选择浙江省义乌市中心医院2021年4月... 目的分析活血通窍汤辅助治疗对动脉瘤性蛛网膜下腔出血(SAH)并发脑血管痉挛(CVS)挛患者临床疗效及对血清基质金属蛋白酶(MMP)-9、同型半胱氨酸(Hcy)和人可溶性细胞间黏附分子-1(sICAM-1)的影响。方法选择浙江省义乌市中心医院2021年4月至2022年4月收治的SAH并发CVS患者78例,运用随机数字表法分为对照组(39例)与治疗组(39例)。对照组给予盐酸法舒地尔注射液治疗,治疗组在对照组基础上服用活血通络汤。2组均治疗2周。比较2组治疗疗效,治疗前后中医证候积分、血流动力学、神经功能和认知功能、MMP-9、Hcy和sICAM-1水平变化。结果治疗组总有效率高于对照组(P<0.05)。2组治疗后患者头痛、恶心呕吐和颈项抵抗积分较治疗前降低(P<0.05),治疗组低于对照组(P<0.05)。2组治疗后颈内动脉颅外段平均注速(VICA-Vm)和大脑中动脉平均注速(MCA-Vm)较治疗前降低(P<0.05),治疗组治疗后低于对照组(P<0.05)。2组治疗后mRS评分较治疗前降低,MoCA评分较治疗前升高(P<0.05);治疗组治疗后改良Rankin量表(mRS)评分低于对照组,蒙特利尔认知评估量表(MoCA)评分高于对照组(P<0.05)。2组治疗后MMP-9、Hcy和sICAM-1水平较治疗前降低(P<0.05);治疗组治疗后MMP-9、Hcy和sICAM-1水平低于对照组(P<0.05)。结论活血通窍汤辅助治疗SAH并发CVS患者疗效良好,患者血流动力学改善,神经功能改善,可降低MMP-9、Hcy和sICAM-1水平。 展开更多
关键词 蛛网膜下腔出血 血管痉挛 颅内 治疗结果 基质金属蛋白酶9 同型半胱氨酸 可溶性细胞间黏附分子-1
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First identification of isatin-β-thiosemicarbazones as novel inhibitors of New Delhi metallo-β-lactamase-1: Chemical synthesis, biological evaluation and molecular simulation 被引量:2
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作者 Guo-Qing Song Wei-Min Wang +2 位作者 Zai-Shun Li Ying Wang Jian-Guo Wang 《Chinese Chemical Letters》 SCIE CAS CSCD 2018年第6期899-902,共4页
New Delhi metallo-b-lactmase-1(NDM-1) catalyzes the hydrolysis of b-lactam antibiotics and cleaves the b-lactam ring of the molecule, conferring bacterial resistance against these medicines. In an effort to discover... New Delhi metallo-b-lactmase-1(NDM-1) catalyzes the hydrolysis of b-lactam antibiotics and cleaves the b-lactam ring of the molecule, conferring bacterial resistance against these medicines. In an effort to discover novel agents to treat this superbug, an old drug methisazone was found to be a weak NDM-1 inhibitor, with an IC50 of 297.6 mmol/L. Based on this result, a series of isatin-β-thiosemicarbazones(IBTs)were synthesized and biologically evaluated as novel NDM-1 inhibitors. Nine of the IBT compounds showed IC50 values of 〈10 mmol/L, the best of which was 2.72 mmol/L. Comparative field analysis(Co MFA) contour maps were generated to depict the structural features and molecular docking was performed to understand the possible binding mode of these inhibitors. The present research hereby has provided valuable information for further discovery of NDM-1 inhibitors. 展开更多
关键词 New Delhi metallo-β-lactmase-1 Isatin-β-thiosemicarbazones In vitro enzyme inhibition Molecular docking
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Activation free energy of Zn(Ⅱ),Co(Ⅱ) binding to metallo-β-lactamase ImiS 被引量:2
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作者 Xia Yang Ya-Jun Zhou +3 位作者 Pei He Yun-Hua Guo Cong-Jun Liu Ke-Wu Yang 《Chinese Chemical Letters》 SCIE CAS CSCD 2014年第10期1323-1326,共4页
In an effort to understand the recombination of a B2 metallo-β-lactamase(MβL),the binding of metals to apo-ImiS was studied by isothermal titration calorimetry and fluorescence spectra.The binding of Zn(Ⅱ),Co... In an effort to understand the recombination of a B2 metallo-β-lactamase(MβL),the binding of metals to apo-ImiS was studied by isothermal titration calorimetry and fluorescence spectra.The binding of Zn(Ⅱ),Co(Ⅱ) to apo-lmiS resulted in activation free energies △G_≠~θ values of 93.719 and 92.948 kJ mol^(-1),respectively,and increasing of fluorescence intensity at maxima emission of 340 nm. 展开更多
关键词 Antibiotic resistant bacteria metallo-β-lactamases metalloprotein recombinant Thermokinetic parameters
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