Ceftazidime-avibactam, meropenen-vaborbactam, and imipenem-relebactam in combination with aztreonam against multidrug-resistant, metallo-β-lactamase-producing Klebsiella pneumoniae

Eur J Clin Microbiol Infect Dis. 2021 Aug;40(8):1755-1759. doi: 10.1007/s10096-021-04197-3. Epub 2021 Feb 17.

Abstract

The spread of multidrug-resistant (MDR), metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae represents a major therapeutic challenge. The newly introduced β-lactam-β-lactamase inhibitors (BLBLIs), ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) are inactive against MBLs. The aim of this study was to evaluate the in vitro efficacy of aztreonam (ATM) in combination with CAZ/AVI, M/V, and I/R against 40 MDR, MBL-producing, and serine-β-lactamases co-producing Klebsiella pneumoniae using the Etest method. Synergy was defined as a fractional inhibitory concentration index ≤0.5. All isolates were resistant to ATM, CAZ/AVI, and I/R and 38/40 (95%) were resistant to M/V. Synergy was observed in 97.5% in the combinations CAZ/AVI-ATM, and I/R-ATM and in 72.5% in the combination M/V-ATM. Further clinical studies are required to confirm the efficacy of these antimicrobial combinations.

Keywords: Aztreonam; Carbapenem resistance; Ceftazidime/avibactam; Imipenem/relebactam; Klebsiella pneumoniae; MBL; Meropenem/vaborbactam; Synergy.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / pharmacology
  • Aztreonam / pharmacology
  • Boronic Acids / pharmacology
  • Ceftazidime / pharmacology
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial*
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Humans
  • Imipenem / administration & dosage
  • Imipenem / pharmacology
  • Klebsiella pneumoniae / drug effects*
  • Meropenem / pharmacology
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Boronic Acids
  • Drug Combinations
  • Heterocyclic Compounds, 1-Ring
  • avibactam, ceftazidime drug combination
  • meropenem and vaborbactam
  • Imipenem
  • Ceftazidime
  • Meropenem
  • Aztreonam
  • relebactam