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In Vitro Effectiveness of Meropenem and Cefmetazole Combination Treatment Against KPC-2-Producing Enterobacteriaceae

Hideharu Hagiya1, Kotaro Aoki2, Yukihiro Akeda1

  • 11 Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University, Osaka, Japan.

Microbial Drug Resistance (Larchmont, N.Y.)
|March 6, 2019
PubMed

Insights

The combination of meropenem and cefmetazole shows potential bactericidal effects against KPC-producing Enterobacteriaceae. This novel combination therapy warrants further investigation for treating infections caused by these challenging bacteria.

Area of Science:

  • Antimicrobial resistance
  • Infectious diseases
  • Pharmacology

Background:

  • Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant threat due to limited effective treatment options.
  • Optimal therapeutic strategies for CPE infections remain to be established.
  • Meropenem (MEM) and cefmetazole (CMZ) combination therapy is explored as a potential alternative.

Purpose of the Study:

  • To evaluate the in vitro efficacy of meropenem (MEM) and cefmetazole (CMZ) combination against blaKPC-2-positive Enterobacteriaceae.
  • To compare the efficacy of MEM-CMZ combination with double-carbapenem therapy using ertapenem (ERT).
  • To assess the synergistic, bactericidal, and morphological effects of MEM-CMZ combination.

Main Methods:

  • Checkerboard assays were performed on 11 blaKPC-2-positive Enterobacteriaceae isolates to determine synergistic effects (fractional inhibitory concentration index ≤0.5).
  • Time-kill assays using Klebsiella pneumoniae BAA-1705 evaluated bactericidal activity (≥10^3 CFU/mL reduction in 24 hr).
  • Scanning electron microscopy (SEM) was utilized to observe bacterial morphological changes induced by the drug combination.

Main Results:

  • Synergistic effects were observed in 7 out of 11 isolates with the MEM-CMZ combination, whereas no synergy was found with MEM-ERT.
  • MEM-CMZ combination demonstrated a 4-8 fold decrease in MEM's minimum inhibitory concentration (MIC).
  • MEM-CMZ exhibited bactericidal effect at 0.25x MIC each, while MEM-ERT showed regrowth; SEM revealed bacterial cell lysis with MEM-CMZ.

Conclusions:

  • The combination of meropenem and cefmetazole demonstrates significant in vitro synergistic and bactericidal activity against KPC-producing Enterobacteriaceae.
  • MEM-CMZ combination therapy shows promise as a potential treatment against infections caused by blaKPC-2-positive Enterobacteriaceae.
  • Further clinical investigations are warranted to validate the efficacy of this combination regimen.
Keywords:
cephamycindouble-carbapenem therapy

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