| Description |
Avibactam sodium is a covalent, reversible β-lactamase inhibitor, inhibits β-lactamase TEM-1 and CTX-M-15 with IC50 of 8 nM and 5 nM, respectively. |
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| IC50 & Target |
IC50: 8 nM (TEM-1), 5 nM (CTX-M-15)[1] |
| In Vitro |
Avibactam (NXL104) sodium is a molecule with little antibacterial activity, that inhibits class A and C β-lactamases. Avibactam inactivates most important β-lactamases except metallo types and Acinetobacter OXA carbapenemases[2]. |
| In Vivo |
Avibactam sodium displays a slow return of activity with an off-rate of 0.045±0.022 min-1, which converts to a residence time half-life (tt1/2) of 16±8 min. The measured off-rate for Avibactam suggests that slow deacylation through hydrolysis or reversibility is occurring, and it is in contrast to previously reported extremely long t1/2 values of >1 or >7 d for Avibactam inhibition of TEM-1[1]. Avibactam is a new promising β-lactamase inhibitor, to overcome resistance caused by β-lactamases. Mice are infected with ca.106 CFU of Pseudomonas aeruginosa intramuscularly into the thigh or intranasally to cause pneumonia and are given 8 different (single) subcutaneous doses of Ceftazidime and Avibactam in various combined concentrations, ranging from 1 to 128 mg/kg of body weight in 2-fold increases. The mean estimated half-life in plasma of Ceftazidime in the terminal phase is 0.28 h (SD, 0.02 h), and that of Avibactam is 0.24 h (SD, 0.04 h). Volumes of distribution are 0.80 liters/kg (SD, 0.14 liters/kg) and 1.18 liters/kg (SD, 0.34 liters/kg), respectively[3]. |
| References |
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| Preparing Stock Solutions |
Please refer to the solubility information to select the appropriate solvent.
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| Kinase Assay
[1] |
In a 200 μL reaction volume, 1 μM TEM-1 is incubated with and without 5 μM Avibactam for 5 min at 37°C and subjected to two ultrafiltration cartridge (UFC) steps to remove excess inhibitor (Ultrafree-0.5 with Biomax membrane, 5-kDa cutoff). Centrifugation at 10,600× g for 8 min is performed at 4°C. After each ultrafiltration step, 20 μL retentate are diluted with 180 μL assay buffer to restore the original enzyme concentration. After two UFC treatments, the amount of free Avibactam is quantified by liquid chromotography/MS/MS and found to be <5% of="" the="" original="" concentration.="" loss="" of="" protein="" during="" ufc="" is="" assessed="" by="" measuring="" tem-1="" activity="" (on="" 4,000-fold="" dilution)="" in="" the="" acyl-enzyme="" sample="" compare="" with="" non-ufc-treated="" enzyme,="" and="" loss="" is="" found="" to="" be=""><>[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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| Cell Assay
[2] |
Avibactam is prepared in sterile water[2]. Cells (~109 cfu) from overnight broth culture are spread on Mueller-Hinton agar supplemented with either (i) Ceftaroline plus Avibactam (1 or 4 mg/L) at 1-16× the MICs or (ii) Ceftaroline at 1 or 4 mg/L plus Avibactam at 1-8× the concentration needed to reduce the Ceftaroline MIC to 1 or 4 mg/L. Colonies are counted after overnight incubation and representatives are retained[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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| Animal Administration
[3] |
Avibactam is reconstituted in sterile water to a stock solution of 5120 mg/L and further solution is prepared in Mueller-Hinton broth (Mice)[3]. Mice[3] |
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| References |
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| Molecular Weight |
287.23 |
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| Formula |
C₇H₁₀N₃NaO₆S |
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| CAS No. |
1192491-61-4 |
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| Storage |
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| Shipping | Room temperature in continental US; may vary elsewhere |
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| Solvent & Solubility |
DMSO: ≥ 30 mg/mL
* "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation=""> |
Purity: 99.99%
COA (96 KB) HNMR (1172 KB) RP-HPLC (240 KB) LCMS (145 KB)
Handling Instructions (1252 KB)-
[1]. Ehmann DE, et al. Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor. Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11663-8.
[2]. Livermore DM, et al. Characterization of β-lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam (NXL104). J Antimicrob Chemother. 2012 Jun;67(6):1354-8.
[3]. Berkhout J, et al. Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infected mice. Antimicrob Agents Chemother. 2015 Apr;59(4):2299-304.
