Experiences in fosfomycin susceptibility testing and resistance mechanism determination in Escherichia coli from urinary tract infections in the UK

J Med Microbiol. 2019 Feb;68(2):161-168. doi: 10.1099/jmm.0.000901. Epub 2018 Dec 13.

Abstract

Purpose: With an increase in the numbers of bacterial isolates resistant to first-line antibiotics, there has been a revival in the use of older drugs including fosfomycin with novel mechanisms of action. We aimed to investigate the prevalence and genotypic nature of fosfomycin resistance in Escherichia coli from urinary tract infections (UTIs) using the various methods available in the clinical microbiology laboratory.

Methodology: In total, 1000 culture-positive urine samples were assessed for the presence of E. coli and fosfomycin susceptibility was determined using the MAST Uri system, microbroth dilution, agar dilution and E-test strips.Results/Key findings. Initial investigation using breakpoint susceptibility testing on the MAST Uri system identified 62 of 657 (9.5 %) E. coli isolates as fosfomycin-resistant (MIC≥32 µg ml-1). However, on further testing, a lower rate of eight of the 62 (1.3 %) were robustly confirmed to be resistant using microbroth dilution, agar dilution and E-test strips. These true resistant isolates belonged to diverse E. coli multi-locus sequence types and each had a unique set of chromosomal alterations in genes associated with fosfomycin resistance. Fosfomycin-resistant isolates were not multiply drug resistant and did not carry plasmidic fosfomycin resistance genes. Therefore, the use of fosfomycin may be unlikely to drive selection of a particular clone or movement of transferrable resistance genes.

Conclusion: Fosfomycin remains a viable option for the treatment of E. coli in uncomplicated UTIs; different susceptibility testing platforms can give very different results regarding the prevalence of fosfomycin resistance, with false positives being a potential problem that may unnecessarily limit the use of this agent.

Keywords: antibiotic resistance; fosfomycin; susceptibility testing.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / genetics
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Colony Count, Microbial
  • Disk Diffusion Antimicrobial Tests
  • Drug Resistance, Bacterial / genetics
  • Escherichia coli / classification
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology*
  • Fosfomycin / pharmacology*
  • Fosfomycin / therapeutic use
  • Humans
  • Microbial Sensitivity Tests
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology*
  • Whole Genome Sequencing

Substances

  • Amino Acids
  • Anti-Bacterial Agents
  • Fosfomycin