In vivo study assessed meropenem and amikacin combination therapy against carbapenem-resistant and carbapenemase-producing Enterobacteriaceae strains

Abstract Objective: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

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An In Vitro and In Vivo Study of Combination Therapy with Photogem®-Mediated Photodynamic Therapy and Cisplatin on Mouse Cancer Cells (CT-26)

Photomedicine and Laser Surgery ◽

10.1089/pho.2009.2750 ◽

2011 ◽

Vol 29 (3) ◽

pp. 155-160 ◽

Cited By ~ 10

Author(s):

Ruifeng Ge ◽

Jin-Chul Ahn ◽

Jang-In Shin ◽

Chan Woong Bahk ◽

Peijie He ◽

...

Keyword(s):

Photodynamic Therapy ◽

Combination Therapy ◽

Cancer Cells ◽

In Vivo Study

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Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae

Microorganisms ◽

10.3390/microorganisms8121964 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1964

Author(s):

Ya-Ting Chang ◽

Tsung-Ying Yang ◽

Po-Liang Lu ◽

Shang-Yi Lin ◽

Liang-Chun Wang ◽

...

Keyword(s):

Combination Therapy ◽

Klebsiella Pneumoniae ◽

Therapeutic Option ◽

Rapid Evolution ◽

Toxicity Testing ◽

World Health ◽

Synergistic Activity ◽

Carbapenem Resistant

Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of ≤0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT–colistin combination could be a potentially favorable therapeutic option for treating CCRKP.

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Bactericidal Efficacy of Meropenem in Combination with Cefmetazole against IMP-producing Carbapenem-Resistant Enterobacteriaceae

10.21203/rs.2.15806/v1 ◽

2019 ◽

Author(s):

Ryuichiro Abe ◽

Hideharu Hagiya ◽

Yukihiro Akeda ◽

Norihisa Yamamoto ◽

Yoshikazu Ishii ◽

...

Keyword(s):

Combination Therapy ◽

Animal Studies ◽

Bactericidal Effect ◽

E Coli ◽

Carbapenem Resistant ◽

Enterobacter Hormaechei ◽

Time Kill ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Objective: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against IMP-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

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594 ERYTHROID DIFFERENTIATION IS SUPPRESSED BY RIBAVIRIN DURING COMBINATION THERAPY WITH PEGYLATED INTERFERON-α2a IN CHRONIC HEPATITIS C: AN IN VITRO AND IN VIVO STUDY

Journal of Hepatology ◽

10.1016/s0168-8278(09)60596-1 ◽

2009 ◽

Vol 50 ◽

pp. S218

Author(s):

A. Aghemo ◽

L. Ronzoni ◽

M.G. Rumi ◽

G.M. Prati ◽

S. Monico ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Combination Therapy ◽

Chronic Hepatitis C ◽

Erythroid Differentiation ◽

Pegylated Interferon ◽

In Vivo Study ◽

Interferon Α2a

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Combination therapy using Smac peptide and doxorubicin-encapsulated MUC 1-targeted polymeric nanoparticles to sensitize cancer cells to chemotherapy: An in vitro and in vivo study

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2020.119650 ◽

2020 ◽

Vol 587 ◽

pp. 119650 ◽

Cited By ~ 1

Author(s):

Mojgan Nejabat ◽

Farhad Eisvand ◽

Fatemeh Soltani ◽

Mona Alibolandi ◽

Seyed Mohammad Taghdisi ◽

...

Keyword(s):

Combination Therapy ◽

Cancer Cells ◽

Polymeric Nanoparticles ◽

In Vivo Study

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Bactericidal efficacy of meropenem in combination with cefmetazole against IMP-producing carbapenem-resistant Enterobacteriaceae

BMC Research Notes ◽

10.1186/s13104-019-4779-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Ryuichiro Abe ◽

Hideharu Hagiya ◽

Yukihiro Akeda ◽

Norihisa Yamamoto ◽

Yoshikazu Ishii ◽

...

Keyword(s):

Combination Therapy ◽

Animal Studies ◽

Bactericidal Effect ◽

The Novel ◽

E Coli ◽

Carbapenem Resistant ◽

Enterobacter Hormaechei ◽

Time Kill

Abstract Objective Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

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