Quinolone Antibiotics Induce Shiga Toxin-Encoding Bacteriophages, Toxin Production, and Death in Mice

J Infect Dis. 2000 Feb;181(2):664-70. doi: 10.1086/315239.

Abstract

Shiga toxin-producing Escherichia coli (STEC) cause significant disease; treatment is supportive and antibiotic use is controversial. Ciprofloxacin but not fosfomycin causes Shiga toxin-encoding bacteriophage induction and enhanced Shiga toxin (Stx) production from E. coli O157:H7 in vitro. The potential clinical relevance of this was examined in mice colonized with E. coli O157:H7 and given either ciprofloxacin or fosfomycin. Both antibiotics caused a reduction in fecal STEC. However, animals treated with ciprofloxacin had a marked increase in free fecal Stx, associated with death in two-thirds of the mice, whereas fosfomycin did not. Experiments that used a kanamycin-marked Stx2 prophage demonstrated that ciprofloxacin, but not fosfomycin, caused enhanced intraintestinal transfer of Stx2 prophage from one E. coli to another. These observations suggest that treatment of human STEC infection with bacteriophage-inducing antibiotics, such as fluoroquinolones, may have significant adverse clinical consequences and that fluoroquinolone antibiotics may enhance the movement of virulence factors in vivo.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / toxicity*
  • Bacterial Toxins / biosynthesis*
  • Bacterial Toxins / genetics
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / toxicity*
  • Coliphages / drug effects*
  • Coliphages / genetics
  • Coliphages / physiology
  • Disease Models, Animal
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology*
  • Escherichia coli Infections / mortality
  • Escherichia coli O157 / drug effects*
  • Escherichia coli O157 / metabolism
  • Escherichia coli O157 / virology
  • Fosfomycin / pharmacology
  • Humans
  • Intestines / virology
  • Male
  • Mice
  • Shiga Toxins

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Bacterial Toxins
  • Shiga Toxins
  • Fosfomycin
  • Ciprofloxacin