Quinolone resistance from a transferable plasmid

Lancet. 1998 Mar 14;351(9105):797-9. doi: 10.1016/S0140-6736(97)07322-4.


Background: Bacteria can mutate to acquire quinolone resistance by target alterations or diminished drug accumulation. Plasmid-mediated resistance to quinolones in clinical isolates has been claimed but not confirmed. We investigated whether a multiresistance plasmid could transfer resistance to quinolones between bacteria.

Methods: We transferred resistance between strains by conjugation. The resistance plasmid was visualised in different hosts by agarose-gel electrophoresis. We determined the frequency of spontaneous mutations to ciprofloxacin or nalidixic-acid resistance in Escherichia coli strains, with or without the quinolone resistance plasmid.

Findings: A multiresistance plasmid (pMG252) from a clinical isolate of Klebsiella pneumoniae was found to increase quinolone resistance to minimum inhibitory concentrations (MICs) as high as 32 microg/mL for ciprofloxacin when transferred to strains of K pneumoniae deficient in outer-membrane porins. Much lower resistance was seen when pMG252 was introduced into K pneumoniae or E coli strains with normal porins. The plasmid had a wide host range and expressed quinolone resistance in other enterobacteriaceae and in Pseudomonas aeruginosa. From a plasmid-containing E coli strain with ciprofloxacin MIC of 0.25 microg/mL and nalidixic-acid MIC of 32 microg/mL, quinolone-resistant mutants could be obtained at more than 100 times the frequency of a plasmid-free strain, reaching MICs for ciprofloxacin of 4 microg/mL and for nalidixic acid of 256 microg/mL.

Interpretation: Transferable resistance to fluoroquinines and nalidixic acid has been found in a clinical isolate of K pneumoniae on a broad host range plasmid. Although resistance was low in wild-type strains, higher levels of quinolone resistance arose readily by mutation. Such a plasmid can speed the development and spread of resistance to these valuable antimicrobial agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Ciprofloxacin / pharmacology
  • Conjugation, Genetic
  • Drug Resistance, Microbial / genetics*
  • Drug Resistance, Multiple / genetics*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Humans
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Nalidixic Acid / pharmacology
  • Plasmids / genetics*


  • Anti-Infective Agents
  • Nalidixic Acid
  • Ciprofloxacin