In vitro efficacy of ceftazidime-avibactam, aztreonam-avibactam and other rescue antibiotics against carbapenem-resistant Enterobacterales from the Arabian Peninsula

Int J Infect Dis. 2020 Oct:99:253-259. doi: 10.1016/j.ijid.2020.07.050. Epub 2020 Jul 29.

Abstract

Objectives: Our aim was to assess the susceptibility of carbapenem-resistant Enterobacterales (CRE) from the Arabian Peninsula to a broad spectrum of antibiotics, including fosfomycin, ceftazidime-avibactam, and aztreonam-avibactam.

Methods: 1192 non-repeat CRE isolated in 2009-2017 from 33 hospitals in five countries of the Arabian Peninsula were tested. The minimum inhibitory concentration of 14 antibiotics was determined. Carbapenemase and 16S methylase genes were detected by PCR. Clonality was assessed by PFGE.

Results: The highest rate of susceptibility was detected to aztreonam-avibactam (95.5%) followed by colistin (79.8%), fosfomycin (71.8%) and tigecycline (59.9%). Isolates co-producing two carbapenemases (12.4%) were the least susceptible. Aminoglycoside susceptibility was affected by the frequent production of a 16S methylase. Susceptibility to ceftazidime-avibactam was impacted by the high rate of metallo-beta-lactamase producers (46.3%), while aztreonam-avibactam resistance occurred mostly in clonally unrelated, carbapenemase non-producing Escherichia coli.

Conclusion: Of the currently available drugs: colistin, tigecycline, and ceftazidime-avibactam co-administered with aztreonam appear to be the most effective to treat CRE infections. However, the presence of non-clonal CRE isolates, in which avibactam does not lower the aztreonam MIC below the clinical breakpoint, is of notable concern. Based on the relatively high rate of fosfomycin susceptibility, it would be desirable to license parenteral fosfomycin in the region.

Keywords: Aztreonam-avibactam; Carbapenem-resistant Enterobacterales; Ceftazidime-avibactam; Colistin; Fosfomycin.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Aztreonam / pharmacology*
  • Bacterial Proteins
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Carbapenem-Resistant Enterobacteriaceae / genetics
  • Carbapenems / pharmacology
  • Ceftazidime / pharmacology*
  • Drug Combinations
  • Drug Resistance, Bacterial / genetics
  • Fosfomycin / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Middle East
  • Tigecycline / pharmacology
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Bacterial Proteins
  • Carbapenems
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Fosfomycin
  • Tigecycline
  • avibactam
  • Ceftazidime
  • beta-Lactamases
  • carbapenemase
  • Aztreonam