Sniffing out resistance - Rapid identification of urinary tract infection-causing bacteria and their antibiotic susceptibility using volatile metabolite profiles

J Pharm Biomed Anal. 2019 Apr 15:167:59-65. doi: 10.1016/j.jpba.2019.01.044. Epub 2019 Jan 31.

Abstract

Antibiotic resistance is set to be an unprecedented threat to modern medicine. 'Sniffing' bacteria potentially offers a rapid way to determine susceptibility. A successful proof-of-principle study is described, using thermal desorption-gas chromatography-mass spectrometry (TDGCMS) to 'smell' cephalexin and ciprofloxacin resistant and sensitive Urinary Tract Infection (UTI)-causing bacteria. 578 peaks at unique retention times were detected from 86 chromatograms of 18 bacterial isolates (E. coli, K. pneumoniae and P. aeruginosa). The isolates were grown with and without the presence of antibiotic. Chi-square analysis found 9 compounds that differed significantly between cephalexin sensitive and resistant isolates, and 22 compounds that differed significantly between ciprofloxacin sensitive and resistant isolates, at p ≤ 0.05. When antibiotic was added to the media, more differences were found in the cephalexin group, attributed to lysis, but not in the ciprofloxacin group. Further work with large sample sizes will potentially enable the development of diagnostic algorithms using presence/absence of particular compounds of interest.

Keywords: Antibiotic; Cephalexin; Ciprofloxacin; Gas chromatography; Mass spectrometry; Metabolite; Profiles; Resistance; Smell; Susceptibility; Thermal desorption; Urinary tract infection; Volatile.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Infections / microbiology*
  • Cephalexin / pharmacology
  • Ciprofloxacin / pharmacology
  • Drug Resistance, Bacterial / drug effects*
  • Escherichia coli / drug effects
  • Escherichia coli / isolation & purification
  • Escherichia coli / metabolism
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / isolation & purification
  • Klebsiella pneumoniae / metabolism
  • Proof of Concept Study
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / isolation & purification
  • Pseudomonas aeruginosa / metabolism
  • Urinary Tract Infections / microbiology*
  • Volatile Organic Compounds / analysis*

Substances

  • Anti-Bacterial Agents
  • Volatile Organic Compounds
  • Ciprofloxacin
  • Cephalexin