Mecillinam
(Synonyms: 美西林,Amdinocillin; FL 1060) 目录号 : GC45932
A β-lactam antibiotic
Cas No.:32887-01-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mecillinam is a β-lactam antibiotic.1 It is active against Gram-negative bacteria, including E. coli, K. pneumoniae, and N. gonorrhoeae (MIC90s = 4, 8, and 1 μg/ml, respectively). It is also active against clinical isolates of E. coli, K. pneumoniae, and P. mirabilis isolated from human urine.2 It binds to K. pneumoniae penicillin-binding protein 2 (PBP2) over PBP1A/B, PBP3, PBP4, and PBP5/6 (IC50s = <0.0075, >256, 128, >256, and >256 mg/L, respectively) in a competitive binding assay.3 Mecillinam is efficacious against susceptible E. coli strains in a systemic mouse model of infection with 50% protective dose (PD50) values ranging from less than or equal to 0.39 to 6.4 mg/kg.4
|1. Neu, H.C. Amdinocillin: A novel penicillin. Antibacterial activity, pharmacology and clinical use. Pharmacotherapy 5(1), 1-10 (1985).|2. Fuchs, F., and Hamprecht, A. Results from a prospective in vitro study on the mecillinam (amdinocillin) susceptibility of Enterobacterales. Antimicrob. Agents Chemother 63(4), e02402-02418 (2019).|3. Sutaria, D.S., Moya, B., Green, K.B., et al. First penicillin-binding protein occupancy patterns of β-lactams and β-lactamase inhibitors in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 62(6), e00282-00218 (2018).|4. Anderson, J.D., Eftekhar, F., Cleeland, R., et al. Comparative activity of mecillinam and ampicillin singly and in combination in the urinary bladder model and experimental mouse model. J. Antimicrob. Chemother. 8(2), 121-131 (1981).
| Cas No. | 32887-01-7 | SDF | |
| 别名 | 美西林,Amdinocillin; FL 1060 | ||
| Canonical SMILES | O=C(O)[C@@H](C(C)(C)S1)N2[C@@]1([H])[C@H](N=CN3CCCCCC3)C2=O | ||
| 分子式 | C15H23N3O3S | 分子量 | 325.4 |
| 溶解度 | Chloroform: 30 mg/ml | 储存条件 | 4°C, protect from light, stored under nitrogen |
| 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 | 3.0731 mL | 15.3657 mL | 30.7314 mL |
| 5 mM | 0.6146 mL | 3.0731 mL | 6.1463 mL |
| 10 mM | 0.3073 mL | 1.5366 mL | 3.0731 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。
Activity of Mecillinam against carbapenem-resistant Enterobacterales
J Antimicrob Chemother 2022 Sep 30;77(10):2835-2839.PMID:35815675DOI:10.1093/jac/dkac226.
Background: Despite the fact that carbapenem-resistant Enterobacterales (CRE) mostly cause urinary tract infections (UTIs), only few studies have focused on the efficacity of Mecillinam against these CRE. Objectives: To evaluate the Mecillinam susceptibility of a huge collection of CRE, including carbapenemase-producing Enterobacterales (CPE) and non-CPE (ESBL and AmpC producers with decreased permeability of the outer membrane). Methods: A total of 8310 non-duplicate clinical CRE, including 4042 OXA-48-like producers, 1094 NDM producers, 411 VIM producers, 174 KPC producers, 42 IMI producers, 153 multiple-carbapenemase producers and 45 isolates producing other types of carbapenemases (such as IMP-like enzymes or GES-5), were included in the study. WGS was performed on all CPE using Illumina technology. Categorization of susceptibility to Mecillinam was performed using disc diffusion (Mecillinam discs at 10 μg; I2A, France) according to EUCAST recommendations. The results were interpreted according to EUCAST guidelines (S ≥15 mm). Results: Significantly higher susceptibility rates were observed for carbapenem-resistant Proteus spp. (85%) and carbapenem-resistant Escherichia coli (84%), which are the two most common species responsible for UTIs, than for Klebsiella pneumoniae (67%), Enterobacter cloacae complex (75%), Citrobacter spp. (65%), Serratia spp. (34%) and Morganella morganii (12%). Susceptibility rates were 84%, 71% and 91% for OXA-48-like, NDM and IMI producers and 70% for non-CPE CRE. Mecillinam was less active against VIM and KPC producers (14% and 0%, respectively). Conclusions: Mecillinam might be an alternative for the treatment of infections due to CRE, particularly UTIs, except for VIM and KPC producers and for M. morganii and Serratia spp species.
Serum levels of Mecillinam in patients with severely impaired renal function
Scand J Infect Dis 1980;12(4):303-5.PMID:6256847DOI:10.3109/inf.1980.12.issue-4.11.
12 patients with severe renal insufficiency were treated for urinary tract infection with 400 mg of Mecillinam intravenously every 6 h. High serum concentrations of Mecillinam were found 6 h after the first morning dose on day 2 and day 5 of the treatment period (mean values 11.4 and 14.5 microgram/ml respectively), and a serum half-life of 334 min. In spite of reduced elimination of the drug, a nearly steady state was achieved within the first few days of treatment. Side effects were not observed.
Intravenous Mecillinam compared with other β-lactams as targeted treatment for Escherichia coli or Klebsiella spp. bacteraemia with urinary tract focus
J Antimicrob Chemother 2021 Jan 1;76(1):206-211.PMID:32989447DOI:10.1093/jac/dkaa411.
Background: Mecillinam (amdinocillin) is active against Gram-negative bacteria. Clinical data on the efficacy of IV Mecillinam for severe urinary tract infections is sparse. Objectives: To assess the effectiveness of targeted IV Mecillinam compared with other β-lactams for bacteraemia with Escherichia coli and Klebsiella spp. and a urinary tract focus. Patients and methods: We performed a retrospective cohort study at five university hospitals in the Capital Region of Denmark from 1 January 2012 to 31 December 2017. We used Cox proportional hazard regression to compare the primary composite endpoint (all-cause mortality or bacteraemia recurrence within 30 days) between patients treated with Mecillinam versus ampicillin, cefuroxime, piperacillin/tazobactam and meropenem. Results: We included 1129 patients in the primary analysis, of which 146 were given IV Mecillinam as targeted treatment. We found no significant difference in the primary endpoint between patients treated with Mecillinam versus ampicillin and cefuroxime, but found a higher risk for the primary endpoint in the piperacillin/tazobactam and meropenem groups, with adjusted HRs of 2.22 (95% CI 1.24-3.97, P < 0.01) and 2.48 (95% CI 1.04-5.93, P = 0.04), respectively, compared with Mecillinam. Conclusions: The results of this study suggest that IV Mecillinam may be a suitable targeted treatment for bacteraemia with a urinary tract focus. However, these results need confirmation by randomized controlled studies.
LC-MS/MS methods for determination of unstable pivmecillinam and Mecillinam in acidified human plasma: Application to a pharmacokinetic study
J Sep Sci 2022 Jul;45(14):2543-2554.PMID:35593582DOI:10.1002/jssc.202200070.
Pivmecillinam, the ester of biologically active antibiotic Mecillinam, is an effective oral preparation to treat urinary tract infections. To study pharmacokinetics in humans, LC-MS/MS methods were developed to quantify pivmecillinam and Mecillinam in human plasma, respectively. Considering cephalexin as internal standard, analytes were separated on UltimateXB-C18 columns after protein precipitation by acetonitrile. The mobile phase was composed of water containing 0.1% formic acid and methanol. The multiple reactions monitoring transitions of m/z 440.2→167.1, 326.1→167.1, and 348.1→158.1 were selected to inspect pivmecillinam, Mecillinam, and the internal standard in positive ion mode. No apparent matrix effect was perceived. Linearities were obtained over calibration ranges of 0.0500-12.0 and 10.0-15,000 ng/mL, respectively. The intraday precisions were below 5.5%, the interday precisions were below 6.1%, and accuracies were within -8.1 to 13.0%. Stability tests were conducted and an acidification step was explored to enhance the stability of pivmecillinam and Mecillinam. Further stability was validated under various storage and processing conditions. Both methods were applied to a pharmacokinetic study of pivmecillinam and Mecillinam after oral administration of 400 mg pivmecillinam hydrochloride tablets in healthy Chinese subjects.
Activity of Mecillinam alone and in combination with other beta-lactam antibiotics
Antimicrob Agents Chemother 1980 Dec;18(6):906-12.PMID:6263179DOI:10.1128/AAC.18.6.906.
The in vitro activities of Mecillinam, ticarcillin, cefamandole, and cefoxitin, singly and in all possible combinations, against 53 clinical isolates were studied by a checkerboard method of determining minimal inhibitory concentrations. For selected representative strains, bactericidal activity was determined by minimal bactericidal concentrations and killing curves. Mecillinam was the least active antibiotic against gram-positive cocci, Pseudomonas aeruginosa, and Bacteroides fragilis and the most active against Enterobacteriaceae. Reproducibility of Mecillinam minimal inhibitory concentrations for susceptible Enterobacteriaceae was often poor, however, due to minor variations in inoculum size. When Mecillinam resistance was observed with Enterobacteriaceae, partial inhibition could be demonstrated at concentrations below minimal inhibitory concentrations, and bacterial cells were consistently ovoid or round; under those conditions the addition of a second study antibiotic resulted in marked synergistic inhibition and killing which was independent of inoculum size and susceptibility to the second antibiotic. In contrast, synergy with Mecillinam against mecillinam-susceptible strains or with other antibiotic combinations against any species was not consistently observed.