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Updated: Jan 4, 2026

Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
Bactericidal efficacy of meropenem in combination with cefmetazole against IMP-producing carbapenem-resistant
Ryuichiro Abe1,2,3, Hideharu Hagiya4,5, Yukihiro Akeda1,2
1Department of Infection Control and Prevention, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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.
Insights
Combination therapy with meropenem (MEM) and cefmetazole (CMZ) showed synergistic and bactericidal effects against carbapenem-resistant Enterobacteriaceae (CRE) producing Imipenemase (IMP) in vitro. This novel combination warrants further investigation for clinical use.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant global health threat due to extensive antibiotic resistance.
- Imipenemase (IMP)-producing CRE are particularly challenging to treat with existing antibiotics.
Purpose of the Study:
- To evaluate the in vitro efficacy of a combination therapy using meropenem (MEM) and cefmetazole (CMZ) against IMP-producing CRE.
- To assess the synergistic and bactericidal potential of MEM/CMZ against specific strains of Enterobacteriaceae harboring blaIMP-1 and blaIMP-6.
Main Methods:
- Utilized the checkerboard method to determine synergistic effects of MEM/CMZ.
- Employed time-killing assays to assess bactericidal activity.
- Tested 26 IMP-producing CRE isolates, including Enterobacter hormaechei, Escherichia coli, and Klebsiella pneumoniae.
Main Results:
- The MEM/CMZ combination demonstrated synergy against all tested IMP-producing CRE isolates.
- Time-kill assays confirmed a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE.
- In vitro results suggest potential efficacy of MEM/CMZ against IMP-1- or IMP-6-producing CRE.
Conclusions:
- The MEM/CMZ combination therapy shows promise as an effective treatment against IMP-producing CRE in vitro.
- Further in vivo and clinical studies are necessary to validate the therapeutic potential of this combination.
- This research contributes to the development of novel strategies to combat multidrug-resistant infections.
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