Investigation of In-vitro Efficacy of Intravenous Fosfomycin in Extensively Drug-Resistant Klebsiella pneumoniae Isolates and Effect of Glucose 6-Phosphate on Sensitivity Results

Int J Antimicrob Agents. 2022 Jan;59(1):106489. doi: 10.1016/j.ijantimicag.2021.106489. Epub 2021 Nov 27.

Abstract

Background: The aim of this study was to determine the in vitro efficacy of intravenous (IV) fosfomycin against extensively drug-resistant Enterobacterales strains and the effect of glucose 6-phosphate (G6-P) on sensitivity results.

Material method: Thirty-two extensively drug-resistant Klebsiella pneumonia strains were included in the study. Detection of the carbapenemase genes was performed using the Gene-Xpert® System Carba R® kit. Susceptibility of IV fosfomycin was assessed using the agar dilution method. The agar dilution method was repeated using Muller-Hinton Agar medium without G6-P to assess the effect of G6-P on sensitivity results.

Results: All strains in the study produced carbapenemases and were resistant to all drugs tested, including carbapenems, piperacillin-tazobactam, ceftriaxone, and ceftazidime. Fosfomycin resistance was detected in 3 (9.3%) strains. When the sensitivity test was repeated without G6-P, fosfomycin resistance was detected in 82.7% of the fosfomycin-susceptible strains. The Gene-Xpert® System showed NDM-1 in 46.8%, OXA-48 in 18.7%, KPC in 3.1%, and NDM-1 + OXA-48 in 21.8% of the strains. OXA-48 was detected in one of the resistant strains, and none of the viable genes were detected in two of the resistant strains.

Conclusion: This study shows that IV fosfomycin is a potentially important treatment alternative for infections caused by common resistant strains. Accurate results may not be obtained unless G6-P is used in the agar dilution method for in vitro susceptibility studies of fosfomycin.

Keywords: Carbapenem-Resistant Enterobacterales; Fosfomycin; Klebsiella pneumoniae; glucose 6-phosphate.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Intravenous
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Carbapenem-Resistant Enterobacteriaceae / genetics*
  • Fosfomycin / administration & dosage
  • Fosfomycin / therapeutic use*
  • Genetic Variation
  • Genotype
  • Glucose-6-Phosphate / metabolism
  • Humans
  • Klebsiella Infections / drug therapy*
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics*

Substances

  • Anti-Bacterial Agents
  • Fosfomycin
  • Glucose-6-Phosphate