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Avibactam

Manufactured by Merck Group
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Avibactam is a novel beta-lactamase inhibitor developed by Merck Group. It is designed to be used in combination with certain antibiotics to enhance their effectiveness against a range of bacteria that produce beta-lactamases, enzymes that can break down and deactivate beta-lactam antibiotics.

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Lab products found in correlation

Piperacillin, by Merck Group (1 mentions) Tazobactam, by Chem-Impex (1 mentions) Relebactam, by Merck Group (1 mentions) Iso sensitest agar, by Thermo Fisher Scientific (1 mentions) Ertapenem, by Merck Group (1 mentions) Ceftolozane, by Merck Group (1 mentions) Ca edta, by Merck Group (1 mentions) Mhiib, by Merck Group (1 mentions) Clavulanic acid, by Merck Group (1 mentions) Clavulanate, by Merck Group (1 mentions) Meropenem, by Merck Group (1 mentions) Vaborbactam, by Merck Group (1 mentions) Amoxicillin, by Merck Group (1 mentions) Ceftazidime, by Merck Group (1 mentions) Faropenem, by Merck Group (1 mentions) Atcc 19977, by American Type Culture Collection (1 mentions) Imipenem, by Merck Group (1 mentions)

Close spelling variants of this product

Ceftazidime-avibactam

6 protocols using avibactam

1

Identifying BL Resistance Mechanisms in CPO Isolates

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Bacterial isolates of human CPO infection were acquired from the CDC and FDA Antibiotic Resistance Isolate Bank. The BL resistance mechanisms, including the β-lactamase production, were identified by analyzing the whole genome sequence of the isolates with the Resistance Gene Identifier of the Comprehensive Antibiotic Resistance Database (McArthur et al., 2013 (link); Alcock et al., 2020 (link)). The information of the genome sequences (i.e., sequence accession numbers) of the tested isolates was provided by the CDC and FDA Antibiotic Resistance Isolate Bank, and is available on the official website of this isolate bank. Three BLIs (clavulanate, vaborbactam, avibactam) and their clinically combined partner BLs (amoxicillin for clavulanate; meropenem for vaborbactam; ceftazidime for avibactam) were purchased from Sigma-Aldrich. To facilitate comparison, all BLIs were tested at the same concentration attainable in patient plasma (50μm) (Carlier et al., 2013 (link); Nicolau et al., 2015 (link); Lee et al., 2019 (link)).
Feng Y., de Vos A.L., Khan S., St. John M, & Hasan T. (2021). Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams. Frontiers in Microbiology, 12, 756410.
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2

Evaluation of β-Lactam Combinations

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Piperacillin was obtained from Sigma-Aldrich (St. Louis, MO). Tazobactam was purchased from Chem-Impex International (Wood Dale, IL). Relebactam and avibactam were obtained from Merck (Whitehouse Station, NJ) and Allergan (Bridgewater, NJ), respectively. Stock solutions were prepared in sterile water and stored at −80°C before use. Two CTX-M-15 producing K. pneumoniae (Kp3 and KpK91) and an SHV-12-producing E. coli (EcF65) obtained from a reference microbiology laboratory (Madrid, Spain) were used along with a locally sourced K. pneumoniae harbouring CTX-M-15 (Kp2301). These isolates were previously confirmed to display the ESBL phenotype and showed different susceptibilities to Tazobactam inhibition.
Abodakpi H., Chang K.T., Zhou J., Byerly C, & Tam V.H. (2019). A Novel Framework to Compare the Effectiveness of β-lactamase Inhibitors against Extended-Spectrum β-lactamase-producing Enterobacteriaceae. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 25(9), 1154.e9-1154.e14.
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3

Antibiotic susceptibility testing protocol

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Zidebactam, ertapenem, ceftolozane and avibactam were from Wockhardt (Aurangabad, India); other antibiotics were from Alpha Aesar (Heysham, UK) or Merck KGaA (Gillingham, UK). MICs were determined by BSAC agar dilution on IsoSensitest agar (Oxoid, Basingstoke, UK) 13 and interpreted versus current (v.10.0) EUCAST guidance. 14 Certificates of Analysis data were provided for each antibiotic, irrespective of source, and were used to derive potencies (as per CLSI guidance), with appropriate correction factors then used when preparing antibiotic dilutions. Cefepime/zidebactam was tested as a 1:1 ratio; tazobactam was used at a fixed 4 mg/L in combinations with ceftolozane and piperacillin; avibactam at a fixed 4 mg/L combined with ceftazidime. Across 33 sets of MIC testing plates for eight antibiotics there were just nine instances where values for one of the four control strains (Escherichia coli ATCC 25922 and ATCC 35218, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 700603) fell outside the accepted control limits.
Mushtaq S., Garello P., Vickers A., Woodford N, & Livermore D.M. (2021). Activity of cefepime/zidebactam (WCK 5222) against 'problem' antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory. The Journal of antimicrobial chemotherapy, 76(6).
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4

Antibiotic Stock Solution Preparation

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Imipenem, meropenem, ertapenem, doripenem, ceftazidime–avibactam, aztreonam, and Ca-EDTA (Sigma‒Aldrich) were used to prepare stock solutions <24 h before use. All agents were dissolved in cation-adjusted Müller–Hinton II broth (MHIIB) (Sigma‒Aldrich), and the solutions were sterilized through a syringe filter with a membrane nominal pore size of 0.22 μm. Serial dilutions of the antibiotic and Ca-EDTA stocks were prepared in MHIIB immediately before use.
Wannigama D.L., Sithu Shein A.M., Hurst C., Monk P.N., Hongsing P., Phattharapornjaroen P., Fox Ditcham W.G., Ounjai P., Saethang T., Chantaravisoot N., Wapeesittipan P., Luk-in S., Sae-Joo S., Nilgate S., Rirerm U., Tanasatitchai C., Kueakulpattana N., Laowansiri M., Liao T., Kupwiwat R., Rojanathanes R., Ngamwongsatit N., Tungsanga S., Leelahavanichkul A., Devanga Ragupathi N.K., Badavath V.N., Hosseini Rad S.M., Kanjanabuch T., Hirankarn N., Storer R.J., Cui L., Amarasiri M., Ishikawa H., Higgins P.G., Stick S.M., Kicic A., Chatsuwan T, & Abe S. (2023). Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiellapneumoniae infections. iScience, 26(7), 107215.
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5

Evaluation of Inhibitor Quality

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The inhibitors
sulbactam, avibactam, and clavulanic acid were purchased
from Sigma-Aldrich, MedChemExpress, and Matrix Scientific, respectively.
It was found that quality can vary between suppliers.
van Alen I., Chikunova A., Safeer A.A., Ahmad M.U., Perrakis A, & Ubbink M. (2021). The G132S Mutation Enhances the Resistance of Mycobacterium tuberculosis β-Lactamase against Sulbactam. Biochemistry, 60(28), 2236-2245.
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6

Evaluation of Imipenem, Faropenem, and Avibactam Against M. abscessus

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The M. abscessus reference strain ATCC 19977 (ATCC, Manassas, VA) as well as 20 deidentified clinical strains obtained from patients at the Johns Hopkins Hospital15 (link),16 (link) were used for this study. The clinical isolates have been identified to the sub-species level26 (link) and the MICs of many other β-lactams against these strains have been published15 (link),21 (link). The strains were grown in Middlebrook 7H9 broth (Difco) supplemented with 0.5% glycerol, 10% albumin-dextrose-NaCl enrichment, and 0.05% Tween-80, at 37 °C with constant shaking at 220 RPM in an orbital shaker. Imipenem, faropenem, and avibactam were obtained from Sigma-Aldrich.
Batchelder H.R., Story-Roller E., Lloyd E.P., Kaushik A., Bigelow K.M., Maggioncalda E.C., Nuermberger E.L., Lamichhane G, & Townsend C.A. (2020). Development of a penem antibiotic against Mycobacteroides abscessus. Communications Biology, 3, 741.
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