A Randomized, Open-label, Single-dose, 3-period Crossover Study to Describe the Pharmacokinetic Parameters of BLI-489 and Piperacillin When Administered Simultaneously Compared to When Each is Administered Alone.

The purpose of this study is to evaluate how BLI-489 and piperacillin interact when given together to healthy subjects.

Start Date01 May 2009

Sponsor / Collaborator

Wyeth AB

NCT00854009 / CompletedPhase 1

Ascending Single Dose Study of the Safety, Tolerability, and Pharmacokinetics of BLI-489 Administered Intravenously to Healthy Japanese Male Subjects

The purpose of this study is to evaluate the safety and tolerability of single doses of BLI-489 administered intravenously in healthy Japanese male subjects, and how the drug is absorbed and eliminated.

Start Date20 Feb 2009

Sponsor / Collaborator

Wyeth AB

100 Clinical Results associated with BLI-489

100 Translational Medicine associated with BLI-489

100 Patents (Medical) associated with BLI-489

Literatures (Medical) associated with BLI-489

27 Apr 2022·Journal of Antimicrobial ChemotherapyQ2 · MEDICINE

Synergistic effect of the novel β-lactamase inhibitor BLI-489 combined with imipenem or meropenem against diverse carbapenemase-producing carbapenem-resistant Enterobacterales

Q2 · MEDICINE

Article

Author: Xu, Mengxin ; Zhou, Tieli ; Zhang, Ying ; Yao, Zhuocheng ; Shi, Shiyi ; Zhou, Cui ; Ye, Jianzhong ; Liu, Qi ; Zhang, Xiaodong ; Zhou, Beibei

AbstractObjectivesTo investigate the antibacterial activity of the novel β-lactamase inhibitor BLI-489 combined with imipenem or meropenem against diverse carbapenemase-producing carbapenem-resistant Enterobacterales (CRE) in vivo and in vitro.MethodsTwenty-five CRE strains, including Klebsiella pneumoniae (n = 10), Escherichia coli (n = 6) and Enterobacter cloacae (n = 9), were used in chequerboard assays to evaluate the synergistic effect of BLI-489 combined with imipenem or meropenem. A cytotoxicity test was used to detect the toxicity of BLI-489 monotherapy or combination therapy. Three isolates producing class A, B and D carbapenemases, respectively, were selected to further confirm the synergistic effect in vitro by time–kill assays and in vivo by the Galleria mellonella infection model.ResultsChequerboard assays demonstrated that BLI-489 combined with imipenem had a synergistic effect on 7/10, 7/9 and 5/6 of carbapenem-resistant K. pneumoniae, E. cloacae and E. coli, respectively, while BLI-489 and meropenem had a synergistic effect on 8/10, 9/9 and 6/6 of the isolates, respectively. No cytotoxicity was observed when BLI-489 was used alone or in combination with imipenem or meropenem at the test concentrations. In the time–kill assays, combination therapy had a synergistic effect on DC5114 carrying blaKPC-2, FK8401 carrying blaNDM-5 and CG996 carrying blaOXA-23. The synergistic effect in vivo was confirmed by the G. mellonella infection model.ConclusionsThe novel β-lactamase inhibitor BLI-489 possesses a synergistic effect against diverse carbapenemase-producing CRE combined with imipenem or meropenem.

19 Jan 2021·Journal of Antimicrobial ChemotherapyQ2 · MEDICINE

In vitro and in vivo activities of imipenem combined with BLI-489 against class D β-lactamase-producing Acinetobacter baumannii

Q2 · MEDICINE

Article

Author: Huang, Shu-Wei ; Chen, Te-Li ; Lee, Yi-Tzu ; Lee, I-Ming ; Kuo, Shu-Chen ; Wang, Fu-Der ; Chiang, Ming-Hsien ; Yang, Ya-Sung ; Wang, Yung-Chih ; Su, Ying-Shih ; Chiu, Chun-Hsiang

AbstractBackgroundAccording to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like β-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb).ObjectivesIn the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D β-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined.MethodsA chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time–kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model.ResultsChequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time–kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice.ConclusionsImipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

15 Jul 2017·FEMS Microbiology LettersQ4 · BIOLOGY

Relationship between β-lactamase production and resistance phenotype in Klebsiella pneumoniae strains

Q4 · BIOLOGY

Article

Author: Ahn, Juhee ; Kim, Jeongjin ; Ding, Tian

This study was designed to evaluate the resistance phenotypes of β-lactamases-producing Klebsiella pneumoniae strains. The antibiotic susceptibility and β-lactamase activity of K. pneumoniae strains, including antibiotic-sensitive K. pneumoniae (KPWT), ciprofloxacin-induced resistant K. pneumoniae (KPCIP) and clinically isolated K. pneumoniae strains (KPCI237, KPCI263 and KPCI272) were determined in the absence and presence of β-lactamase inhibitors (BLI 489, sulbactam, clavulanate and tazobactam). All strains were highly resistant to ampicillin in the absence of β-lactamase inhibitors (MIC≥ 512 μg mL-1). In the presence of clavulanate, the MICs of ampicillin and piperacillin against KPWT were decreased by > 64-fold and 4-fold, respectively. The resistance of KPCI263 to cefotaxime, ceftazidime, ceftriaxone and piperacillin were increased in the presence of BLI-489. The antibiotic susceptibility of KPCI237 to β-lactams was not noticeably changed in the presence of β-lactamase inhibitor (clavulanate, sulbactam or tazobactam). KPWT, KPCIP and KPCI272 were positive for blaSHV, blaAmpC and blaFOX/MOX; KPCI237 for blaSHV and blaAmpC; and KPCI263 for blaSHV and blaOXA-48. The antibiotic susceptibility corresponded well with the results obtained from dual disc diffusion assay, which was in good agreement with the β-lactamase production. The results provide useful information for understanding the resistance phenotypes in association with β-lactamase production.

100 Deals associated with BLI-489

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