Synonym
NXL104; NXL-104; NXL 104; Avibactam; Avibactam sodium.
IUPAC/Chemical Name
sodium (2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate
InChi Key
RTCIKUMODPANKX-JBUOLDKXSA-M
InChi Code
InChI=1S/C7H11N3O6S.Na/c8-6(11)5-2-1-4-3-9(5)7(12)10(4)16-17(13,14)15;/h4-5H,1-3H2,(H2,8,11)(H,13,14,15);/q;+1/p-1/t4-,5+;/m1./s1
SMILES Code
O=C1N(OS(=O)(O[Na])=O)[C@H]2CN1[C@H](C(N)=O)CC2
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
The compound functions by forming a reversible covalent bond with the active site serine of β-lactamases, inhibiting their hydrolytic activity without being degraded, and has shown clinical utility in complicated intra-abdominal and urinary tract infections caused by resistant pathogens
Biological target:
Avibactam sodium (NXL-104) is a covalent and reversible non-β-lactam β-lactamase inhibitor which inhibits β-lactamase TEM-1 and CTX-M-15 with IC50s of 8 nM and 5 nM, respectively.
In vitro activity:
The potential of avibactam and clavulanate for induction of ampC expression was evaluated on the three E. cloacae strains at 16–64 mg/L. Clavulanate had no significant effects on 293UC1 and 293LA2 strains during the 6-hour incubation period (Figure 2B and E), whereas it was a moderate ampC inducer for 293HT107 with about a 40-fold increase of ampC mRNA at 64 mg/L after 2 hours of incubation (Figure 2H). In contrast, avibactam had no detectable effect on ampC mRNA levels in the three strains tested (Figure 2, C,F, and I). At the concentrations used for induction studies, avibactam had no effect on the growth of the bacterial strains tested, as testified by the OD values measured at each time point.
Reference: Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11663-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857152/
In vivo activity:
AVI (Avibactam) sensitization of NDM-1–producing K. pneumoniae to killing by cathelicidin, serum, neutrophils and platelets, suggested potential utility in vivo despite absent activity as a sole agent in the standard MIC testing paradigm. Although this study’s mouse model was relatively resistant to lung infection by the NDM-1–producing K. pneumoniae isolate, it was found in pilot studies that a high bacterial inoculum (1 × 109 CFU/mL) resulted in >50% mortality within 72 hours (Supplementary Figure 2). Using this challenge dose, this study used a humanized dosing regimen corrected for the increased murine elimination half-life of AVI (ie, 80 mg/kg administered 1 hour after infection and then every 8 hours thereafter for a total of 3 doses). AVI monotherapy led to a modest (ie, 0.8-log) but statistically significant reduction in the number of NDM-1–producing K. pneumoniae CFU recovered from lungs 30 hours after challenge (Figure 4D). Similar findings were seen across KPC-producing K. pneumoniae strains at lower bacterial inoculums (5 × 108 CFU/mL; Figure 4D).
Reference: J Infect Dis. 2019 Jul 2;220(3):484-493. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603980/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
87.0 |
302.90 |
| Water |
53.5 |
186.27 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
287.22
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Wang DY, Abboud MI, Markoulides MS, Brem J, Schofield CJ. The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam. Future Med Chem. 2016 Jun;8(10):1063-84. doi: 10.4155/fmc-2016-0078. Epub 2016 Jun 21. PMID: 27327972.
2. Ehmann DE, Jahić H, Ross PL, Gu RF, Hu J, Kern G, Walkup GK, Fisher SL. 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. doi: 10.1073/pnas.1205073109. Epub 2012 Jul 2. PMID: 22753474; PMCID: PMC3406822.
3. Berkhout J, Melchers MJ, van Mil AC, Lagarde CM, Nichols WW, Mouton JW. Evaluation of the post-antibiotic effect in vivo for the combination of a β-lactam antibiotic and a β-lactamase inhibitor: ceftazidime-avibactam in neutropenic mouse thigh and lung infections. J Chemother. 2021 Mar 6:1-9. doi: 10.1080/1120009X.2021.1892365. Epub ahead of print. PMID: 33682636.
4. Ulloa ER, Dillon N, Tsunemoto H, Pogliano J, Sakoulas G, Nizet V. Avibactam Sensitizes Carbapenem-Resistant NDM-1-Producing Klebsiella pneumoniae to Innate Immune Clearance. J Infect Dis. 2019 Jul 2;220(3):484-493. doi: 10.1093/infdis/jiz128. PMID: 30923801; PMCID: PMC6603980.
In vitro protocol:
1. Wang DY, Abboud MI, Markoulides MS, Brem J, Schofield CJ. The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam. Future Med Chem. 2016 Jun;8(10):1063-84. doi: 10.4155/fmc-2016-0078. Epub 2016 Jun 21. PMID: 27327972.
2. Ehmann DE, Jahić H, Ross PL, Gu RF, Hu J, Kern G, Walkup GK, Fisher SL. 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. doi: 10.1073/pnas.1205073109. Epub 2012 Jul 2. PMID: 22753474; PMCID: PMC3406822.
In vivo protocol:
1. Berkhout J, Melchers MJ, van Mil AC, Lagarde CM, Nichols WW, Mouton JW. Evaluation of the post-antibiotic effect in vivo for the combination of a β-lactam antibiotic and a β-lactamase inhibitor: ceftazidime-avibactam in neutropenic mouse thigh and lung infections. J Chemother. 2021 Mar 6:1-9. doi: 10.1080/1120009X.2021.1892365. Epub ahead of print. PMID: 33682636.
2. Ulloa ER, Dillon N, Tsunemoto H, Pogliano J, Sakoulas G, Nizet V. Avibactam Sensitizes Carbapenem-Resistant NDM-1-Producing Klebsiella pneumoniae to Innate Immune Clearance. J Infect Dis. 2019 Jul 2;220(3):484-493. doi: 10.1093/infdis/jiz128. PMID: 30923801; PMCID: PMC6603980.
1: Das S, Li J, Riccobene T, Carrothers TJ, Newell P, Melnick D, Critchley IA, Stone GG, Nichols WW. Dose Selection and Validation for Ceftazidime-Avibactam in Adults with Complicated Intra-abdominal Infections, Complicated Urinary Tract Infections, and Nosocomial Pneumonia. Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e02187-18. doi: 10.1128/AAC.02187-18. Print 2019 Apr. Review. PubMed PMID: 30670413; PubMed Central PMCID: PMC6437548.
2: Giri P, Patel H, Srinivas NR. Review of Clinical Pharmacokinetics of Avibactam, A Newly Approved non-β lactam β-lactamase Inhibitor Drug, In Combination Use With Ceftazidime. Drug Res (Stuttg). 2019 May;69(5):245-255. doi: 10.1055/a-0748-5548. Epub 2018 Oct 8. Review. PubMed PMID: 30296806.
3: Sy SKB, Zhuang L, Sy S, Derendorf H. Clinical Pharmacokinetics and Pharmacodynamics of Ceftazidime-Avibactam Combination: A Model-Informed Strategy for its Clinical Development. Clin Pharmacokinet. 2019 May;58(5):545-564. doi: 10.1007/s40262-018-0705-y. Review. PubMed PMID: 30097887.
4: Zhong H, Zhao XY, Zhang ZL, Gu ZC, Zhang C, Gao Y, Cui M. Evaluation of the efficacy and safety of ceftazidime/avibactam in the treatment of Gram-negative bacterial infections: a systematic review and meta-analysis. Int J Antimicrob Agents. 2018 Oct;52(4):443-450. doi: 10.1016/j.ijantimicag.2018.07.004. Epub 2018 Aug 31. Review. PubMed PMID: 30012440.
5: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500953/ PubMed PMID: 30000012.
6: Shirley M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Drugs. 2018 Apr;78(6):675-692. doi: 10.1007/s40265-018-0902-x. Review. PubMed PMID: 29671219.
7: Nichols WW, Newell P, Critchley IA, Riccobene T, Das S. Avibactam Pharmacokinetic/Pharmacodynamic Targets. Antimicrob Agents Chemother. 2018 May 25;62(6). pii: e02446-17. doi: 10.1128/AAC.02446-17. Print 2018 Jun. Review. PubMed PMID: 29610208; PubMed Central PMCID: PMC5971577.
8: Sherry N, Howden B. Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications. Expert Rev Anti Infect Ther. 2018 Apr;16(4):289-306. doi: 10.1080/14787210.2018.1453807. Epub 2018 Mar 21. Review. PubMed PMID: 29543500.
9: Rodriguez BA, Girotto JE, Nicolau DP. Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Novel Therapy for Multidrug Resistant Gram Negative Infections in Children. Curr Pediatr Rev. 2018;14(2):97-109. doi: 10.2174/1573396314666180308150908. Review. PubMed PMID: 29521242.
10: Falcone M, Viale P, Tiseo G, Pai M. Pharmacokinetic drug evaluation of avibactam + ceftazidime for the treatment of hospital-acquired pneumonia. Expert Opin Drug Metab Toxicol. 2018 Mar;14(3):331-340. doi: 10.1080/17425255.2018.1434142. Epub 2018 Jan 31. Review. PubMed PMID: 29373935.
11: Tuon FF, Rocha JL, Formigoni-Pinto MR. Pharmacological aspects and spectrum of action of ceftazidime-avibactam: a systematic review. Infection. 2018 Apr;46(2):165-181. doi: 10.1007/s15010-017-1096-y. Epub 2017 Nov 7. Review. PubMed PMID: 29110143.
12: Yaeger A, Kappes J. Pharmacotherapy Review of Ceftazidime-Avibactam. S D Med. 2017 May;70(5):229-231. Review. PubMed PMID: 28813756.
13: Barber KE, Ortwine JK, Akins RL. Ceftazidime/Avibactam: Who Says You Can't Teach an Old Drug New Tricks? J Pharm Pharm Sci. 2016 Oct - Dec;19(4):448-464. doi: 10.18433/J3X31R. Review. PubMed PMID: 28057163.
14: Goodlet KJ, Nicolau DP, Nailor MD. Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections. Ther Clin Risk Manag. 2016 Dec 1;12:1811-1826. eCollection 2016. Review. PubMed PMID: 27942218; PubMed Central PMCID: PMC5140030.
15: Buckman SA, Krekel T, Muller AE, Mazuski JE. Ceftazidime-avibactam for the treatment of complicated intra-abdominal infections. Expert Opin Pharmacother. 2016 Dec;17(17):2341-2349. Epub 2016 Oct 31. Review. PubMed PMID: 27758148.
16: Hidalgo JA, Vinluan CM, Antony N. Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Drug Des Devel Ther. 2016 Jul 26;10:2379-86. doi: 10.2147/DDDT.S110946. eCollection 2016. Review. PubMed PMID: 27528799; PubMed Central PMCID: PMC4970634.
17: Falcone M, Paterson D. Spotlight on ceftazidime/avibactam: a new option for MDR Gram-negative infections. J Antimicrob Chemother. 2016 Oct;71(10):2713-22. doi: 10.1093/jac/dkw239. Epub 2016 Jul 17. Review. PubMed PMID: 27432599.
18: Wang DY, Abboud MI, Markoulides MS, Brem J, Schofield CJ. The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam. Future Med Chem. 2016 Jun;8(10):1063-84. doi: 10.4155/fmc-2016-0078. Epub 2016 Jun 21. Review. PubMed PMID: 27327972.
19: van Duin D, Bonomo RA. Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Second-generation β-Lactam/β-Lactamase Inhibitor Combinations. Clin Infect Dis. 2016 Jul 15;63(2):234-41. doi: 10.1093/cid/ciw243. Epub 2016 Apr 20. Review. PubMed PMID: 27098166; PubMed Central PMCID: PMC4928383.
20: Gardiner BJ, Golan Y. Ceftazidime-avibactam (CTZ-AVI) as a treatment for hospitalized adult patients with complicated intra-abdominal infections. Expert Rev Anti Infect Ther. 2016;14(5):451-63. doi: 10.1586/14787210.2016.1173542. Review. PubMed PMID: 27042762.
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2. Hogan AM, Rahman ASMZ, Motnenko A, Natarajan A, Maydaniuk DT, León B, Batun Z, Palacios A, Bosch A, Cardona ST. Profiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium. Nat Commun. 2023 Aug 9;14(1):4815. doi: 10.1038/s41467-023-40494-5. PMID: 37558695; PMCID: PMC10412643.
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