4-alkoxy and 4-thioalkoxyquinoline derivatives as chemosensitizers for the chloramphenicol-resistant clinical Enterobacter aerogenes 27 strain

Int J Antimicrob Agents. 2003 Sep;22(3):270-3. doi: 10.1016/s0924-8579(03)00215-2.

Abstract

Enterobacter aerogenes is a Gram-negative bacteria frequently responsible for nosocomial respiratory tract infections. Strains resistant to chloramphenicol are frequently isolated. Alkoxy and thio-alkoxyquinolines have a potential to act as chemosensitizers that would render multi-drug-resistant (MDR) bacterial infections susceptible to antibiotics to which they were originally resistant. Several new quinoline derivatives have been prepared, characterized and studied for their ability to increase chloramphenicol sensitivity of E. aerogenes 27, a clinical strain that exhibits the MDR phenotype. Drugs investigated were either quinoline ethers or quinoline thio-ethers. Thio-ethers are much more efficient in increasing chloramphenicol sensitivity than other corresponding ethers. In particular, 4-piperidinoethylthio-quinoline increases the strain sensitivity to chloramphenicol by about 20 times at 2 mM concentration. Similarly, sensitivity to quinolone antibiotics dramatically increases. Because these quinoline derivatives act as inhibitors of the drug efflux pump responsible for bacterial resistance to chloramphenicol, they may serve as adjunct to conventional therapy of E. aerogenes infections.

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Biological Transport, Active / drug effects
  • Chloramphenicol / pharmacology*
  • Cross Infection / drug therapy
  • Cross Infection / microbiology
  • Drug Interactions
  • Drug Resistance, Multiple, Bacterial
  • Enterobacter aerogenes / drug effects*
  • Enterobacter aerogenes / isolation & purification
  • Enterobacter aerogenes / metabolism
  • Enterobacteriaceae Infections / drug therapy
  • Enterobacteriaceae Infections / microbiology
  • Humans
  • In Vitro Techniques
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Respiratory Tract Infections / drug therapy
  • Respiratory Tract Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Quinolines
  • Chloramphenicol