Home
  >  
Section 79
  >  
Chapter 78,984

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

Wang, Y.-C.; Huang, S.-W.; Chiang, M.-H.; Lee, I.-M.; Kuo, S.-C.; Yang, Y.-S.; Chiu, C.-H.; Su, Y.-S.; Chen, T.-L.; Wang, F.-D.; Lee, Y.-T.

Journal of Antimicrobial ChemoTherapy 76(2): 451-459

2021

ISSN/ISBN: 1460-2091
PMID: 33057603
DOI: 10.1093/jac/dkaa421
Accession: 078983453
Download citation:  
Text
  |  
BibTeX
  |  
RIS
According 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). In 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. A 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. Chequerboard 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. Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

PDF emailed within 0-6 h: $19.90




Related References

Chiu, C.-H.; Liu, Y.-H.; Wang, Y.-C.; Lee, Y.-T.; Kuo, S.-C.; Chen, T.-L.; Lin, J.-C.; Wang, F.-D. 2016: In vitro activity of SecA inhibitors in combination with carbapenems against carbapenem-hydrolysing class D β-lactamase-producing Acinetobacter baumannii Journal of Antimicrobial ChemoTherapy 71(12): 3441-3448
Jeon, B-Chan.; Jeong, S.Hoon.; Bae, I.Kwon.; Kwon, S.Bong.; Lee, K.; Young, D.; Lee, J.Hun.; Song, J.Seok.; Lee, S.Hee. 2005: Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter baumannii producing the OXA-23 beta-lactamase in korea Journal of Clinical Microbiology 43(5): 2241-2245
Yang, H.Y.; Lee, H.J.; Suh, J.T.; Lee, K.M. 2009: Outbreaks of imipenem resistant Acinetobacter baumannii producing OXA-23 beta-lactamase in a tertiary care hospital in Korea Yonsei Medical Journal 50(6): 764-770
Kouyama, Y.; Harada, S.; Ishii, Y.; Saga, T.; Yoshizumi, A.; Tateda, K.; Yamaguchi, K. 2012: Molecular characterization of carbapenem-non-susceptible Acinetobacter spp. in Japan: predominance of multidrug-resistant Acinetobacter baumannii clonal complex 92 and IMP-type metallo-β-lactamase-producing non-baumannii Acinetobacter species Journal of Infection and Chemotherapy: Official Journal of the Japan Society of ChemoTherapy 18(4): 522-528
Tan, Q.; Ogawa, A.M.; Raghoobar, S.L.; Wisniewski, D.; Colwell, L.; Park, Y.-W.; Young, K.; Hermes, J.D.; Dininno, F.P.; Hammond, M.L. 2011: Thiophenyl oxime-derived phosphonates as nano-molar class C beta-lactamase inhibitors reducing MIC of imipenem against Pseudomonas aeruginosa and Acinetobacter baumannii Bioorganic and Medicinal Chemistry Letters 21(14): 4363-4365
Wareham, D.W.; Bean, D.C. 2006: In vitro activities of polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii Antimicrobial Agents and ChemoTherapy 50(2): 825; Author Reply 825-6
Tripodi, M.-F.; Durante-Mangoni, E.; Fortunato, R.; Utili, R.; Zarrilli, R. 2007: Comparative activities of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases International Journal of Antimicrobial Agents 30(6): 537-540
Yoon, J.; Urban, C.; Terzian, C.; Mariano, N.; Rahal, J.J. 2004: In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii Antimicrobial Agents and ChemoTherapy 48(3): 753-757
Wareham, D.W.; Bean, D.C. 2006: In-vitro activity of polymyxin B in combination with imipenem, rifampicin and azithromycin versus multidrug resistant strains of Acinetobacter baumannii producing OXA-23 carbapenemases Annals of Clinical Microbiology and Antimicrobials 5: 10
Santimaleeworagun, W.; Wongpoowarak, P.; Chayakul, P.; Pattharachayakul, S.; Tansakul, P.; Garey, K.W. 2011: In vitro activity of colistin or sulbactam in combination with fosfomycin or imipenem against clinical isolates of carbapenem-resistant Acinetobacter baumannii producing OXA-23 carbapenemases Southeast Asian Journal of Tropical Medicine and Public Health 42(4): 890-900
Paton, R.; Miles, R.S.; Hood, J.; Amyes, S.G.; Miles, R.S.; Amyes, S.G. 1993: ARi 1: beta-lactamase-mediated imipenem resistance in Acinetobacter baumannii International Journal of Antimicrobial Agents 2(2): 81-87
Hornstein, M. 1997: Oxacillin-hydrolyzing β-lactamase involved in resistance to imipenem in Acinetobacter baumannii FEMS Microbiology Letters 153(2): 333-339
Malekzadegan, Y.; Abdi, A.; Heidari, H.; Moradi, M.; Rastegar, E.; Sedigh Ebrahim-Saraie, H. 2019: In vitro activities of colistin, imipenem and ceftazidime against drug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii isolates in the south of Iran Bmc Research Notes 12(1): 301
Hornstein, M.; Sautjeau-Rostoker, C.; Péduzzi, J.; Vessières, A.; Hong, L.T.; Barthélémy, M.; Scavizzi, M.; Labia, R. 1997: Oxacillin-hydrolyzing beta-lactamase involved in resistance to imipenem in Acinetobacter baumannii Fems Microbiology Letters 153(2): 333-339
Donald, H.M.; Scaife, W.; Amyes, S.G.; Young, H.K. 2000: Sequence analysis of ARI-1, a novel OXA beta-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92 Antimicrobial Agents and ChemoTherapy 44(1): 196-199
Donald, H.M.; Scaife, W.; Amyes, S.G.B.; Young, H.-K. 2000: Sequence Analysis of Ari-1, a Novel Oxa beta -Lactamase, Responsible for Imipenem Resistance in Acinetobacter baumannii 6B92 Antimicrobial Agents and Chemotherapy 44(1): 196-199
Cherubin, C.E.; Eng, R.H.; Smith, S.M.; Tan, E.N. 1991: An in-vitro and in-vivo comparison of the activity of beta-lactamase inhibitor combinations with imipenem and cephalosporins against Escherichia coli producing TEM-1 or TEM-2 beta-lactamase Journal of Antimicrobial ChemoTherapy 28(1): 61-70
Szabó, D.; Máthé, A.; Filetóth, Z.; Anderlik, P.; Rókusz, L.; Rozgonyi, F. 2001: In vitro and in vivo activities of amikacin, cefepime, amikacin plus cefepime, and imipenem against an SHV-5 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain Antimicrobial Agents and ChemoTherapy 45(4): 1287-1291
Carvalhaes, C.G.; Cayô, R.; Assis, D.M.; Martins, E.R.; Juliano, L.; Juliano, M.A.; Gales, A.C. 2013: Detection of SPM-1-producing Pseudomonas aeruginosa and class D β-lactamase-producing Acinetobacter baumannii isolates by use of liquid chromatography-mass spectrometry and matrix-assisted laser desorption ionization-time of flight mass spectrometry Journal of Clinical Microbiology 51(1): 287-290
Brauers, J.; Frank, U.; Kresken, M.; Rodloff, A.C.; Seifert, H. 2005: Activities of various β-lactams and β-lactam/β-lactamase inhibitor combinations against Acinetobacter baumannii and Acinetobacter DNA group 3 strains Clinical Microbiology and Infection 11(1): 24-30