Zidebactam
(Synonyms: 齐德巴坦,WCK-5107) 目录号 : GC34870
A PBP2 inhibitor and β-lactam antibiotic enhancer
Cas No.:1436861-97-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Zidebactam is a penicillin-binding protein 2 (PBP2) inhibitor and β-lactam antibiotic enhancer.1 It inhibits P. aeruginosa PBP2 (IC50 = 0.26 ?g/ml) and is selective for PBP2 over PBP1a, -1b, -3, -4, and -5/6 (IC50s = >4 ?g/ml for all). Zidebactam enhances the bactericidal activity of cefepime against multidrug-resistant strains of P. aeruginosa, as well as against E. coli, Klebsiella, Enterobacter, S. marcescens, and A. baumannii.2 In vivo, zidebactam enhances cefepime-induced reductions in bacterial loads in mouse models of K. pneumoniae-induced peritonitis and thigh infection.3 Formulations containing zidebactam in combination with cefepime have been used in the treatment of various bacterial infections.
1.Moya, B., Barcelo, I.M., Bhagwat, S., et al.WCK 5107 (zidebactam) and WCK 5153 are novel inhibitors of PBP2 showing potent "β-lactam enhancer" activity against Pseudomonas aeruginosa, including multidrug-resistant metallo-β-lactamase-producing high-risk clonesAntimicrob. Agents Chemother.61(6)e02529-02516(2017) 2.Sader, H.S., Rhomberg, P.R., Flamm, R.K., et al.WCK 5222 (cefepime/zidebactam) antimicrobial activity tested against Gram-negative organisms producing clinically relevant β-lactamasesJ. Antimicrob. Chemother.72(6)1696-1703(2017) 3.Moya, B., Barcelo, I.M., Cabot, G., et al.In vitro and in vivo activities of β-lactams in combination with the novel β-lactam enhancers zidebactam and WCK 5153 against multidrug-resistant metallo-β-lactamase-producing Klebsiella pneumoniaeAntimicrob. Agents Chemother.63(5)e00128-00119(2019)
| Cas No. | 1436861-97-0 | SDF | |
| 别名 | 齐德巴坦,WCK-5107 | ||
| Canonical SMILES | O=C([C@@H]1CCCNC1)NNC([C@@H]2CC[C@@H]3C[N@]2C(N3OS(=O)(O)=O)=O)=O | ||
| 分子式 | C13H21N5O7S | 分子量 | 391.4 |
| 溶解度 | Water: 50 mg/mL (127.75 mM) | 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 | 2.5549 mL | 12.7747 mL | 25.5493 mL |
| 5 mM | 0.511 mL | 2.5549 mL | 5.1099 mL |
| 10 mM | 0.2555 mL | 1.2775 mL | 2.5549 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 | ||||||||||
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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。
Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
Front Cell Infect Microbiol 2022 Jul 8;12:918868.PMID:35899052DOI:10.3389/fcimb.2022.918868.
Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested Zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12-512 mg/l) and sulbactam plus 4 mg/l Zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with Zidebactam. The sulbactam/Zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/Zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
Activity of ertapenem/Zidebactam (WCK 6777) against problem Enterobacterales
J Antimicrob Chemother 2022 Sep 30;77(10):2772-2778.PMID:35972407DOI:10.1093/jac/dkac280.
Background: Secondary healthcare will remain pressured for some years, both because SARS-CoV-2 will circulate as a nosocomial pathogen, and owing to backlogs of patients awaiting delayed elective procedures. These stresses will drive the use of Outpatient Parenteral Antibiotic Therapy (OPAT), which will need to cover increasingly resistant Gram-negative opportunists. We evaluated the activity of ertapenem/Zidebactam, proposed for 2 + 2 g q24h administration. Materials and methods: MICs were determined, by BSAC agar dilution, for 1632 Enterobacterales submitted to the UK national reference laboratory for investigation of antimicrobial resistance. Results: Over 90% of Escherichia coli with AmpC, ESBLs, KPC, metallo- or OXA-48 carbapenemases were inhibited by ertapenem/Zidebactam 1:1 at ertapenem's current 0.5 mg/L breakpoint. For other major Enterobacterales, the proportions inhibited by ertapenem/Zidebactam 1:1 at 0.5 mg/L were mostly 65% to 90% but were lower for Klebsiella pneumoniae/oxytoca with metallo- or OXA-48 β-lactamases. However, animal studies support an 8 mg/L breakpoint for ertapenem/Zidebactam, based on a shortened T>MIC being needed compared with ertapenem alone. On this basis ertapenem/Zidebactam would count as active against 90%-100% of isolates in all groups except K. pneumoniae/oxytoca with MBLs (±OXA-48), where MICs and percent susceptibility vary substantially even with inocula within the BSAC acceptable range. Conclusions: Ertapenem/Zidebactam has a proposed once-daily regimen well suited to OPAT. Even on highly conservative breakpoint projections, it has potential against MDR E. coli, including metallo-carbapenemase producers. If trial data sustain the 8 mg/L breakpoint indicated by animal experiments, its potential will extend widely across infections due to ESBL-, AmpC- and carbapenemase-producing Enterobacterales.
Activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/Zidebactam against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa
J Antimicrob Chemother 2022 Sep 30;77(10):2809-2815.PMID:35904000DOI:10.1093/jac/dkac241.
Objectives: To evaluate the activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/Zidebactam against a clinical and laboratory collection of ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa β-lactamase mutants. Methods: The activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam, cefepime/Zidebactam and comparators was evaluated against a collection of 30 molecularly characterized ceftolozane/tazobactam- and/or ceftazidime/avibactam-resistant P. aeruginosa isolates from patients previously treated with cephalosporins. To evaluate how the different β-lactamases in the clinical isolates affected the resistance to these agents, a copy of each blaPDC, blaOXA-2 and blaOXA-10 ancestral and mutant allele from the clinical isolates was cloned in pUCp24 and expressed in dual blaPDC-oprD (for blaPDC-like genes) or single oprD (for blaOXA-2-like and blaOXA-10-like genes) PAO1 knockout mutants. MICs were determined using reference methodologies. Results: For all isolates, MICs were higher than 4 and/or 8 mg/L for ceftolozane/tazobactam and ceftazidime/avibactam, respectively. Cefiderocol was the most active agent, showing activity against all isolates, except one clinical isolate that carried an R504C substitution in PBP3 (MIC = 16 mg/L). Imipenem/relebactam was highly active against all isolates, except two clinical isolates that carried the VIM-20 carbapenemase. Cefepime/Zidebactam and cefepime/taniborbactam displayed activity against most of the isolates, but resistance was observed in some strains with PBP3 amino acid substitutions or that overexpressed mexAB-oprM or mexXY efflux pumps. Evaluation of transformants revealed that OXA-2 and OXA-10 extended-spectrum variants cause a 2-fold increase in the MIC of cefiderocol relative to parental enzymes. Conclusions: Cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/Zidebactam show promising and complementary in vitro activity against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant P. aeruginosa. These agents may represent potential therapeutic options for ceftolozane/tazobactam- and ceftazidime/avibactam-resistant P. aeruginosa infections.
Activity of cefepime/Zidebactam (WCK 5222) against 'problem' antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory
J Antimicrob Chemother 2021 May 12;76(6):1511-1522.PMID:33760082DOI:10.1093/jac/dkab067.
Background: Triple-action diazabicyclooctanes, e.g. Zidebactam, combine β-lactamase inhibition, antibacterial activity, and 'enhancement' of PBP3-targeted β-lactams. Objectives: To examine the activity of cefepime/Zidebactam against consecutive 'problem' Gram-negative bacteria referred to the UK national reference laboratory. Methods: MICs were determined by BSAC agar dilution for 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, categorized by carbapenemase detection and interpretive reading. Results: Universal susceptibility to cefepime/Zidebactam 8 + 8 mg/L was seen for otherwise multidrug-resistant Enterobacterales with AmpC, extended-spectrum, K1, KPC and OXA-48-like β-lactamases, or with impermeability and 'unassigned' mechanisms. Unlike ceftazidime/avibactam and all other comparators, cefepime/Zidebactam 8 + 8 mg/L also inhibited most (190/210, 90.5%) Enterobacterales with MBLs. Resistance in the remaining minority of MBL producers, and in 13/24 with both NDM MBLs and OXA-48-like enzymes, was associated with Klebsiella pneumoniae ST14. For Pseudomonas aeruginosa, MICs of cefepime/Zidebactam rose with efflux grade, but exceeded 8 + 8 mg/L for only 11/85 isolates even in the highly-raised efflux group. Among 103 P. aeruginosa with ESBLs or MBLs, 97 (94.5%) were inhibited by cefepime/Zidebactam 8 + 8 mg/L whereas fewer than 15% were susceptible to any comparator. MICs for Acinetobacter baumannii with acquired OXA carbapenemases clustered around 8 + 8 to 32 + 32 mg/L, with higher values for MBL producers. A strong enhancer effect augmented activity against many isolates that were highly resistant to cefepime and Zidebactam alone and which had mechanisms not inhibited by Zidebactam. Conclusions: Assuming successful clinical trials, cefepime/Zidebactam has scope to widely overcome critical resistances in both Enterobacterales and non-fermenters.
Antimicrobial activity of cefepime/Zidebactam (WCK 5222), a β-lactam/β-lactam enhancer combination, against clinical isolates of Gram-negative bacteria collected worldwide (2018-19)
J Antimicrob Chemother 2022 Sep 30;77(10):2642-2649.PMID:35897129DOI:10.1093/jac/dkac233.
Background: Zidebactam, a bicyclo-acyl hydrazide β-lactam 'enhancer' antibiotic, in combination with cefepime (WCK 5222) is under clinical development for the treatment of resistant Gram-negative infections. Objectives: To evaluate the in vitro activity of cefepime/Zidebactam and comparators against 24 220 Gram-negative bacteria. Methods: Organisms were consecutively collected in 2018-19 from 137 medical centres located in the USA (n = 9140), Western Europe (W-EU; n = 5929), Eastern Europe (E-EU; n = 3036), the Asia-Pacific region (APAC; n = 3791) and Latin America (LATAM; n = 2324). The isolates were susceptibility tested using the broth microdilution method as part of the SENTRY Program. Cefepime/Zidebactam was tested at a 1:1 ratio. Results: Cefepime/Zidebactam was highly active against Enterobacterales (MIC50/90 0.03/0.25 mg/L; 99.9% inhibited at ≤8 mg/L) and retained potent activity against carbapenem-resistant Enterobacterales (CRE) isolates (97.8% inhibited at ≤8 mg/L). CRE rates varied widely from 1.1% in the USA to 1.9% in W-EU, 3.6% in APAC and 14.6% in E-EU (3.9% overall). The most common carbapenemase genes observed overall were blaKPC (37.6% of CRE), blaOXA-48-like (30.0%) and blaNDM (23.8%). Resistance to ceftazidime/avibactam among CRE was elevated in APAC (64.8%), E-EU (25.5%) and LATAM (20.7%). Against Pseudomonas aeruginosa, cefepime/Zidebactam inhibited 99.2% of isolates at ≤8 mg/L and susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was lowest in E-EU (83.9% and 82.0%, respectively). Cefepime/Zidebactam exhibited good activity against Stenotrophomonas maltophilia (80.0% inhibited at ≤8 mg/L) and Burkholderia cepacia (89.4% inhibited at ≤8 mg/L). Conclusions: Cefepime/Zidebactam demonstrated potent in vitro activity against a large worldwide collection of contemporary clinical isolates of Gram-negative bacteria.