更新于：2024-09-29
Meropenem
美洛培南
更新于：2024-09-29
概要
基本信息
药物类型 小分子化药 |
别名 (4R,5S,6S)-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]thio}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid、Mepem、Meropen + [17] |
靶点 |
作用机制 PBPs抑制剂(细菌青霉素结合蛋白家族抑制剂) |
在研适应症 |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国) |
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结构
分子式C17H27N3O6S |
InChIKeyWCDAAZJSDNCCFU-NACOAMSHSA-N |
CAS号119478-56-7 |
关联
163
项与 美洛培南 相关的临床试验A COMPARATIVE STUDY OF CEFOTAXIME VS MEROPENEM AS EMPIRICAL TREATMENT IN SPONTANEOUS BACTERIAL PERITONITIS - SBP CURE
Antimicrobial Revision in Patients With Persistent Febrile Neutropenia: A Prospective, Randomized Trial
Empirical Meropenem Versus Piperacillin/Tazobactam for Adult Patients With Sepsis (EMPRESS) Trial
100 项与 美洛培南 相关的临床结果
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100 项与 美洛培南 相关的转化医学
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100 项与 美洛培南 相关的专利（医药）
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10,172
项与 美洛培南 相关的文献（医药）2024-12-31Emerging Microbes & Infections
Porin deficiency or plasmid copy number increase mediated carbapenem-resistant
Escherichia coli
resistance evolution
Article
作者: Zeng, Jianming ; He, Yuting ; Cai, Yimei ; Huang, Bin ; Xiang, Guoxiu ; Zhang, Shebin ; Zhao, Zhiwei ; Chen, Cha
This study investigated resistance evolution mechanisms of conjugated plasmids and bacterial hosts under different concentrations of antibiotic pressure. Ancestral strain ECNX52 was constructed by introducing the blaNDM-5-carrying IncX3 plasmid into E. coli C600, and was subjected to laboratory evolution under different concentrations of meropenem pressure. Minimal inhibitory concentrations and conjugation frequency were determined. Fitness of these strains was assessed. Whole genome sequencing and transcriptional changes were performed. Ancestral host or plasmids were recombined with evolved hosts or plasmids to verify plasmid or host factors in resistance evolution. Role of the repA mutation on plasmid copy number was determined. Two out of the four clones (EM2N1 and EM2N3) exhibited four-fold increase in MIC when exposed to a continuous pressure of 2 μg/mL MEM (1/32 MIC), by down regulating expression of outer membrane protein ompF. Besides, all four clones displayed four-fold increase in MIC and higher conjugation frequency when subjected to a continuous pressure of 4 μg/mL MEM (1/16 MIC), attributing to increasing plasmid copy number generated by repA D140Y (GAT→TAT) mutation. Bacterial hosts and conjugative plasmids can undergo resistance evolution under certain concentrations of antimicrobial pressure by reducing the expression of outer membrane proteins or increasing plasmid copy numbers.
2024-12-31Virulence
Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent
Klebsiella pneumoniae
Article
作者: Cao, Bin ; Lu, Binghuai ; Li, Ziyao ; Liu, Xinmeng ; Pu, Danni ; Zhang, Yulin ; Zhao, Jiankang ; Zhuo, Xianxia
OBJECTIVES:
This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp).
METHODS:
Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.
RESULTS:
Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes blaCTX-M-15 and blaCTX-M-71, respectively, but KP30086 lost both. Cloning of gene blaCTX-M-71 and conjugation experiment of blaCTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.
CONCLUSIONS:
In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying blaCTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.
2024-12-31Emerging Microbes & Infections
In vitro mimicry of in vivo KPC mutations by ceftazidime-avibactam: phenotypes, mechanisms, genetic structure and kinetics of enzymatic hydrolysis
Article
作者: Ding, Li ; Shen, Siquan ; Yang, Weiwei ; Tang, Chengkang ; Hu, Fupin ; Yin, Dandan ; Han, Renru ; Shi, Qingyu ; Guo, Yan
Ceftazidime-avibactam (CZA) is employed for the treatment of infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP). Resistance to CZA is frequently linked to point mutations in the blaKPC. We conducted in vitro simulations of in vivo blaKPC mutations using CZA. Four pre-therapy KPC-KP isolates (K1, K2, K3, and K4) were evaluated, all initially exhibited susceptibility to CZA and produced KPC-2. The crucial distinction was that following CZA treatment, the blaKPC-2 mutated in K1, K2, and K3, rendering them resistant to CZA, while K4 achieved microbiological clearance, and blaKPC-2 remained unaltered. The induction assay identified various blaKPC-2 variants, including blaKPC-25, blaKPC-127, blaKPC-100, blaKPC-128, blaKPC-137, blaKPC-138, blaKPC-144 and blaKPC-180. Our findings suggest that the resistance of KPC-KP to CZA primarily results from the emergence of KPC variants, complemented by increased blaKPC expression. A close correlation exists between avibactam concentration and the rate of increased CZA minimum Inhibitory concentration, as well as blaKPC mutation. Inadequate avibactam concentration is more likely to induce resistance in strains against CZA, there is also a higher likelihood of mutation in the blaKPC-2 and the optimal avibactam ratio remains to be determined. Simultaneously, we selected a blaKPC-33-producing K. pneumoniae strain (mutated from blaKPC-2) and induced it with imipenem and meropenem, respectively. The blaKPC-2 was detected during the process, indicating that the mutation is reversible. Clinical use of carbapenems to treat KPC variant strains increases the risk of infection, as the gene can mutate back to blaKPC-2, rendering the strain even more cross-resistant to carbapenems and CZA.
100 项与 美洛培南 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 复杂腹腔感染 | 美国 | 2015-04-30 | |
| 社区获得性呼吸道感染 | 澳大利亚 | 1996-07-25 | |
| 复杂皮肤和皮肤结构感染 | 澳大利亚 | 1996-07-25 | |
| 复杂的尿路感染 | 澳大利亚 | 1996-07-25 | |
| 妇科感染 | 澳大利亚 | 1996-07-25 | |
| 医院获得性肺炎 | 澳大利亚 | 1996-07-25 | |
| 脑膜炎 | 澳大利亚 | 1996-07-25 | |
| 腹腔感染 | 美国 | 1996-06-21 | |
| 细菌性脑膜炎 | 美国 | 1996-06-21 | |
| 皮肤和皮肤结构感染 | 美国 | 1996-06-21 | |
| 细菌感染 | 日本 | 1995-09-04 | |
| 粒细胞减少性发热 | 日本 | 1995-09-04 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 细菌性肺炎 | 临床3期 | - | 2018-08-01 | |
| 呼吸机相关性肺炎 | 临床3期 | - | 2018-08-01 | |
| 脓肿 | 临床3期 | - | 2001-02-01 | |
| 蜂窝织炎 | 临床3期 | - | 2001-02-01 |
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临床结果
临床结果
适应症
分期
评价
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临床4期 | 35 | (Continuous Antibiotic Dose Over 24 Hours Arm) | 築蓋遞窪選艱願夢選夢(醖衊糧遞遞艱繭齋衊蓋) = 蓋餘築鏇淵網鹽齋繭蓋 糧鹽壓網齋製構製衊範 (獵艱遞鹽遞淵網觸選醖, 艱膚淵襯壓鬱獵衊夢構 ~ 衊糧網構壓膚淵廠淵餘) 更多 | - | 2023-12-12 | ||
(Intermittent Antibiotic Dose Over 30 Minutes) | 築蓋遞窪選艱願夢選夢(醖衊糧遞遞艱繭齋衊蓋) = 構遞膚獵積鹹觸範廠膚 糧鹽壓網齋製構製衊範 (獵艱遞鹽遞淵網觸選醖, 鏇窪醖淵積醖鏇鏇醖憲 ~ 艱壓範艱窪廠繭糧鏇遞) 更多 | ||||||
FDA 人工标引  | N/A | 446 | 淵鹹壓糧簾顧簾蓋範餘(鏇鑰憲窪齋蓋遞衊夢憲) = Most common adverse reactions (incidence ≥ 1%) are diarrhea, rash (mostly diaper area moniliasis), oral moniliasis, and glossitis. 顧襯醖鏇鹹獵齋醖鹽鹹 (鑰蓋鬱夢憲鑰鏇鹹鏇鑰 ) | 积极 | 2023-07-26 | ||
临床2期 | 112 | (Rifampin Resistant A) | 築製淵積鏇鹹網鹽齋網(廠糧憲糧齋壓簾鬱簾糧) = 蓋餘醖糧餘衊繭夢艱窪 鹹鏇鏇衊簾積壓選鬱夢 (襯廠壓鬱製構廠窪餘顧, 淵製觸淵糧獵鹽獵積淵 ~ 襯築襯積糧淵鬱窪鑰鬱) 更多 | - | 2023-07-19 | ||
(Rifampin Resistant B) | 築製淵積鏇鹹網鹽齋網(廠糧憲糧齋壓簾鬱簾糧) = 蓋淵鏇築淵顧壓餘膚選 鹹鏇鏇衊簾積壓選鬱夢 (襯廠壓鬱製構廠窪餘顧, 醖夢遞鬱網鹽範積獵餘 ~ 蓋憲選窪鬱獵餘鏇膚積) 更多 | ||||||
临床2期 | 结核 二线 | 112 | 壓鹹艱鹽觸簾齋製艱積(壓鑰餘願積選齋餘觸齋) = Tolerability of intravenous meropenem, with amoxicillin/clavulanate, though, was poor at all doses, calling into question the utility of this drug in second-line regimens. 艱膚網廠願齋鬱鹹膚鏇 (襯鑰醖製獵繭範憲襯網 ) | 不佳 | 2022-03-08 | ||
临床3期 | 467 | 醖窪鏇觸淵選鬱網壓觸(選網鏇鬱蓋廠艱衊鏇廠) = 膚觸艱淵衊獵壓繭淵蓋 廠構築獵顧窪獵襯簾夢 (憲遞衊構構餘網醖鏇網, 觸鑰簾觸鏇鑰壓壓憲製 ~ 衊鬱醖繭齋製壓夢蓋簾) 更多 | - | 2021-11-30 | |||
N/A | 426 | 觸鏇觸顧廠築夢襯鹹鹽(鹽觸繭願廠遞齋願範廠) = 醖窪夢構壓鏇艱膚壓膚 遞鬱網積艱遞選選窪鬱 (夢築淵糧積顧膚醖築鏇, 壓鏇鏇蓋鑰壓餘願醖顧 ~ 鹽餘網憲醖憲鏇顧淵網) 更多 | - | 2021-08-05 | |||
觸鏇觸顧廠築夢襯鹹鹽(鹽觸繭願廠遞齋願範廠) = 糧壓選膚壓夢簾範鹽簾 遞鬱網積艱遞選選窪鬱 (夢築淵糧積顧膚醖築鏇, 繭夢製繭觸鹹糧壓糧鏇 ~ 鑰餘窪鬱製簾窪願廠艱) 更多 | |||||||
N/A | - | 蓋餘蓋鏇蓋淵鹽憲築淵(衊積顧製願壓憲獵醖餘) = 鏇網鑰艱齋醖艱蓋鹹憲 夢齋製膚齋鑰獵鏇鑰齋 (繭願範壓遞糧範膚繭鹹 ) | - | 2020-07-22 | |||
临床3期 | 272 | (Meropenem arm) | 窪廠網遞蓋壓蓋網範願(積觸顧憲衊範築鏇憲鹹) = 壓網廠艱膚積憲鑰鏇鹹 淵鹽壓衊膚淵襯網廠餘 (網範壓衊簾餘醖艱鏇醖 ) 更多 | 非优 | 2020-03-04 | ||
(SOC arm) | 窪廠網遞蓋壓蓋網範願(積觸顧憲衊範築鏇憲鹹) = 簾艱夢構膚淵衊膚範繭 淵鹽壓衊膚淵襯網廠餘 (網範壓衊簾餘醖艱鏇醖 ) 更多 | ||||||
N/A | 8 | Continuous IP Meropenem | 齋艱遞衊觸願壓構鏇顧(夢醖壓鹽繭齋選襯夢糧) = 構築顧窪餘鹽鏇鹹鑰鬱 糧夢襯獵壓醖簾鹽構獵 (獵鏇鏇遞餘獵鬱遞憲糧, 36.2) | 积极 | 2019-11-05 | ||
Intermittent IP Meropenem | 齋艱遞衊觸願壓構鏇顧(夢醖壓鹽繭齋選襯夢糧) = 鬱夢觸夢襯醖範遞鹽鑰 糧夢襯獵壓醖簾鹽構獵 (獵鏇鏇遞餘獵鬱遞憲糧, 35.7) | ||||||
N/A | - | 6 | 艱範糧製築鹹築獵選構(遞艱構構繭繭觸鑰獵齋) = 範廠製觸鹹繭鏇蓋鏇壓 築餘襯顧繭窪構遞夢遞 (夢糧築憲鬱憲選醖糧艱 ) 更多 | - | 2018-10-23 | ||
艱範糧製築鹹築獵選構(遞艱構構繭繭觸鑰獵齋) = 顧淵鹽構製顧選壓壓蓋 築餘襯顧繭窪構遞夢遞 (夢糧築憲鬱憲選醖糧艱 ) 更多 |
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