Imipenem
(Synonyms: 亚胺培南) 目录号 : GP11075
A β-lactam antibiotic
Cas No.:64221-86-9
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
| MIC experiment [1]: | |
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Preparation Method |
Susceptibilities of Y. pestis strains were determined by the broth microdilution method according to CLSI M45-A2 |
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Reaction Conditions |
0.04-2mg/L imipenem in 35°C |
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Applications |
The MICs for the Y. pestis strains with imipenem ranged from a low of 0.12 mg/liter to a high of 1.0 mg/liter，the higher is 0.5 mg/liter |
| Cell experiment[2]: | |
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Cell experiment |
THP-1 cells |
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Preparation Method |
THP-1 cells were seeded into 24-well plates, differentiated for 24 h and infected with M. abscessus CIP104536. Imipenem (8 and 32 mg/L) or amoxicillin alone or in combination with relebactam (16 mg/L) or avibactam (16 mg/L) were added to each well. Rifabutin was also studied in combination with imipenem (8 mg/L), imipenem/relebactam or imipenem/avibactam. Imipenem was added every 24 h. |
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Reaction Conditions |
Imipenem (8 and 32 mg/L) was added every 24 h. |
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Applications |
Combination of relebactam with β-lactams led to >128- and 2-fold decreases in the MICs of amoxicillin and imipenem (from 8 to 4 mg/L). In vitro, M. abscessus was not killed by the imipenem/relebactam combination. In contrast, relebactam increased the intracellular activity of imipenem, leading to 88% killing. |
| Animal experiment [3]: | |
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Animal models |
Female C57BL/6 mice (6-8 weeks old, 20-25 g body weight) |
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Preparation Method |
Mice were randomly divided into four groups: the sham-operated mice as the control group, CLP-induced sepsis mice, CLP-induced sepsis mice treated with the low dose of imipenem (25 mg/kg), CLP-induced sepsis mice treated with the high dose of imipenem (125 mg/kg). Imipenem was injected one hour after sepsis induction, repeating the injection every 24 h up to 72 h. |
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Dosage form |
25-200 mg/kg imipenem, repeating the injection every 24 h up to 72 h. |
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Applications |
Sepsis mice treated with a high dose (125 mg/kg) of imipenem showed a significant reduction in bacterial load, while increased liver enzymes, endotoxin level, and inflammatory cytokine production in plasma and liver. Significant reduction in the liver enzymes, bacterial load, endotoxin levels, and inflammatory cytokine levels was observed in the mice treated with a low dose (25 mg/kg) of imipenem. Liver tissue pathology of mice indicated little tissue destruction in the sepsis mice treated with 25 mg/kg of imipenem compared to other groups. Mice receiving 25 mg/kg of imipenem had better survival rate. |
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References: [1]. Heine HS, Louie A, et,al. Evaluation of imipenem for prophylaxis and therapy of Yersinia pestis delivered by aerosol in a mouse model of pneumonic plague. Antimicrob Agents Chemother. 2014 Jun;58(6):3276-84. doi: 10.1128/AAC.02420-14. Epub 2014 Mar 31. PMID: 24687492; PMCID: PMC4068467. [2]. Le Run E, Atze H, et,al. Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab β-lactamase on the in vitro and intracellular efficacy of imipenem. J Antimicrob Chemother. 2020 Feb 1;75(2):379-383. doi: 10.1093/jac/dkz433. PMID: 31637424. [3]. Khosrojerdi A, Soudi S, et,al. Imipenem alters systemic and liver inflammatory responses in CLP- induced sepsis mice in a dose-dependent manner. Int Immunopharmacol. 2021 Apr;93:107421. doi: 10.1016/j.intimp.2021.107421. Epub 2021 Feb 4. PMID: 33548581. |
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Imipenem is a semisynthetic thienamycin. Imipenem is one of the broad-spectrum antibiotics that has a bactericidal action against multiple gram-negative, gram-positive, aerobic, and anaerobic bacteria by binding to penicillin-binding protein 2 (PBP2) and interacting with bacterial cell wall synthesis[2,5].It exerts a bactericidal effects by disrupting cell wall synthesis.
The MICs for the Y. pestis strains with imipenem ranged from a low of 0.12 mg/liter to a high of 1.0 mg/liter,the highest is 0.5 mg/liter[7].Combination of relebactam with β-lactams led to >128- and 2-fold decreases in the MICs of amoxicillin and imipenem (from 8 to 4 mg/L). In vitro, M. abscessus was not killed by the imipenem/relebactam combination. In contrast, relebactam increased the intracellular activity of imipenem, leading to 88% killing[6]. A high dose of imipenem enhanced the interleukin (IL)-1β level [9] and natural killer (NK) cell activity[3].
Dose-dependent effect of subcutaneous administration of imipenem on the inflammatory responses in sepsis mice. A dose of 25 mg/kg imipenem resulted in better pathology, lower inflammatory mediators, and increased survival rate in sepsis mice[1].
亚胺培南是一种半合成的硫霉素。亚胺培南是一种广谱抗生素，通过与青霉素结合蛋白 2 (PBP2) 结合并与细菌细胞壁合成相互作用，对多种革兰氏阴性菌、革兰氏阳性菌、需氧菌和厌氧菌具有杀菌作用 [2,5].通过破坏细胞壁合成发挥杀菌作用。
鼠疫耶尔森菌株与亚胺培南的 MIC 范围从最低的 0.12 毫克/升到最高的 1.0 毫克/升，最高为 0.5 毫克/升[7]。组合relebactam 和 β-内酰胺导致 >；阿莫西林和亚胺培南的 MIC 分别降低 128 倍和 2 倍（从 8 mg/L 到 4 mg/L）。在体外，亚胺培南/relebactam 组合未杀死脓肿分枝杆菌。相比之下，relebactam 增加了亚胺培南的细胞内活性，导致 88% 的杀灭[6]。高剂量亚胺培南可增强白细胞介素 (IL)-1β 水平[9]和自然杀伤 (NK) 细胞活性[3]。
亚胺培南皮下给药对脓毒症小鼠炎症反应的剂量依赖性影响。 25 mg/kg 亚胺培南的剂量可改善脓毒症小鼠的病理学、降低炎症介质并提高存活率[1]。
References:
[1]: Khosrojerdi A, Soudi S, et,al. Imipenem alters systemic and liver inflammatory responses in CLP- induced sepsis mice in a dose-dependent manner. Int Immunopharmacol. 2021 Apr;93:107421. doi: 10.1016/j.intimp.2021.107421. Epub 2021 Feb 4. PMID: 33548581.
[2]: Acar JF, Goldstein FW, et,al. Activity of imipenem on aerobic bacteria. J Antimicrob Chemother. 1983 Dec;12 Suppl D:37-45. doi: 10.1093/jac/12.suppl_d.37. PMID: 6421793.
[3]: Ortega E, de Pablo MA, et,al. Modification of natural immunity in mice by imipenem/cilastatin. J Antibiot (Tokyo). 1997 Jun;50(6):502-8. doi: 10.7164/antibiotics.50.502. PMID: 9268007.
[4]: Ortega E, de Pablo MA, et,al. Modification of acquired immunity in mice by imipenem/cilastatin. J Antimicrob Chemother. 1999 Oct;44(4):561-4. doi: 10.1093/jac/44.4.561. PMID: 10588322.
[5]: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Imipenem-Cilastatin. 2017 Jan 17. PMID: 31644018.
[6]: Le Run E, Atze H, et,al.Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab β-lactamase on the in vitro and intracellular efficacy of imipenem. J Antimicrob Chemother. 2020 Feb 1;75(2):379-383. doi: 10.1093/jac/dkz433. PMID: 31637424.
[7]: Heine HS, Louie A, et,al. Evaluation of imipenem for prophylaxis and therapy of Yersinia pestis delivered by aerosol in a mouse model of pneumonic plague. Antimicrob Agents Chemother. 2014 Jun;58(6):3276-84. doi: 10.1128/AAC.02420-14. Epub 2014 Mar 31. PMID: 24687492; PMCID: PMC4068467.
| Cas No. | 64221-86-9 | SDF | |
| 别名 | 亚胺培南 | ||
| 化学名 | (5R,6S)-3-[2-(aminomethylideneamino)ethylsulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid | ||
| Canonical SMILES | C[C@](O)([H])[C@](C1=O)([H])[C@@](N21)([H])CC(SCCNC=N)=C2C(O)=O | ||
| 分子式 | C12H17N3O4S | 分子量 | 299.35 |
| 溶解度 | Water : 63 mg/mL；DMSO : 1 mg/mL ( 3.15 mM； DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)；Ethanol : Insoluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3406 mL | 16.7029 mL | 33.4057 mL |
| 5 mM | 0.6681 mL | 3.3406 mL | 6.6811 mL |
| 10 mM | 0.3341 mL | 1.6703 mL | 3.3406 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Imipenem
Imipenem is the first of a new class of beta-lactam antibiotics, the carbapenems, to be released for clinical use. It has the broadest antibacterial activity of all antibiotics available for systemic use in humans. It is active against streptococci, methicillin-sensitive staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas. Resistance to imipenem may emerge during treatment of P. aeruginosa infections, as has occurred with other beta-lactam agents; P. maltophilia and P. cepacia are typically resistant to it. Like the penicillins, imipenem has inhibitory activity against enterococci. Daily doses may range from 500 mg to 1 g, every 6 to 8 hours, in patients with normal renal function. The principal toxic effects have been nausea and vomiting, which occur during intravenous infusion, and seizures, which develop in 1 to 3% of treated patients and are likely to occur in the setting of renal insufficiency and underlying disease of the central nervous system. Imipenem should be considered for treatment of mixed bacterial infections and treatment of resistant aerobic gram-negative bacteria that are not susceptible to other beta-lactam agents. In addition to provoking unnecessary toxicity, indiscriminate use of this agent will promote dissemination of resistance against it.
Imipenem-cilastatin
Imipenem-cilastatin, with its broad spectrum of activity and relative safety, offers an excellent alternative for the treatment of many obstetric and gynecologic infections. In addition, the possibilities for intramuscular administration give clinicians additional treatment options. Because of the relatively high cost of imipenem-cilastatin, it should not be considered "first-line" therapy for most obstetric and gynecologic infections at present. Misuse and overuse of imipenem-cilastatin will result in the further development of resistant organisms, as has already been seen with many other antibiotics, and continued monitoring of susceptibility patterns is necessary.
Imipenem
Imipenem-Cilastatin-Relebactam: A Novel β-Lactam-β-Lactamase Inhibitor Combination for the Treatment of Multidrug-Resistant Gram-Negative Infections
Imipenem-cilastatin-relebactam (IMI-REL) is a novel β-lactam-β-lactamase inhibitor combination recently approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intraabdominal infections (cIAIs). Relebactam is a β-lactamase inhibitor with the ability to inhibit a broad spectrum of β-lactamases such as class A and class C β-lactamases, including carbapenemases. The addition of relebactam to imipenem restores imipenem activity against several imipenem-resistant bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. Clinical data demonstrate that IMI-REL is well tolerated and effective in the treatment of cUTIs and cIAIs due to imipenem-resistant bacteria. In a phase III trial comparing IMI-REL with imipenem plus colistin, favorable clinical response was achieved in 71% and 70% of patients, respectively. Available clinical and pharmacokinetic data support the approved dosage of a 30-minute infusion of imipenem 500 mg-cilastatin 500 mg-relebactam 250 mg every 6 hours, along with dosage adjustments based on renal function. In this review, we describe the chemistry, mechanism of action, spectrum of activity, pharmacokinetics and pharmacodynamics, and clinical efficacy, and safety and tolerability of this new agent. The approval of IMI-REL represents another important step in the ongoing fight against multidrug-resistant gram-negative pathogens.
New Perspectives on Antimicrobial Agents: Imipenem-Relebactam
Imipenem (IMI)/cilastatin/relebactam (REL) (I/R) is a novel β-lactam/β-lactamase inhibitor combination with expanded microbiologic activity against carbapenem-resistant non-Morganellaceae Enterobacterales (CR-NME) and difficult-to-treat (DTR) Pseudomonas aeruginosa. Relebactam, a bicyclic diazabicyclooctane, has no direct antimicrobial activity but provides reliable inhibition of many Ambler class A and class C enzymes. It is currently approved for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) and those with complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) when limited or no alternative treatments are available. Given the number of recently approved β-lactams with expanded activity against highly resistant Gram-negative pathogens, this review summarizes the published literature on I/R, with a focus on its similar and distinguishing characteristics relative to those of other recently approved agents. Overall, available data support its use for the treatment of patients with HABP/VABP, cUTI, and cIAI due to CR-NME and DTR P. aeruginosa. Data indicate that I/R retains some activity against CR-NME and DTR P. aeruginosa isolates that are resistant to the newer β-lactams and vice versa, suggesting that susceptibility testing be performed for all the newer agents to determine optimal treatment options for patients with CR-NME and DTR P. aeruginosa infections. Further comparative PK/PD and clinical studies are warranted to determine the optimal role of I/R, alone and in combination, for the treatment of patients with highly resistant Gram-negative infections. Until further data are available, I/R is a potential treatment for patients with CR-NME and DTR P. aeruginosa infections when the benefits outweigh the risks.