In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enterococci

J Infect Dis. 2004 Dec 15;190(12):2162-6. doi: 10.1086/425580. Epub 2004 Nov 16.

Abstract

We compared ceftriaxone and piperacillin-tazobactam at doses ranging from 0.1 to 2 times the human equivalent daily dose (HEDD), to determine their impact on gastrointestinal colonization by ampicillin- and vancomycin-resistant Enterococcus faecium C68 in a mouse model. Ceftriaxone failed to promote colonization at doses up to 0.25 times the HEDD, whereas piperacillin-tazobactam promoted colonization at doses up to 0.5 times the HEDD. Ceftriaxone promoted colonization at doses at least 0.5 times the HEDD, whereas piperacillin-tazobactam inhibited colonization at doses at least 0.75 times the HEDD. Both piperacillin-tazobactam and ceftriaxone inhibited colonization by an enterococcal strain devoid of low-affinity penicillin-binding protein-5 (significantly increasing its susceptibility to these agents), at doses that promoted colonization by E. faecium C68. These results support a model in which the impact that different beta -lactam agents have on colonization by VRE is related to the level of the beta -lactam agent's intrinsic antienterococcal activity against the colonizing strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Carrier State / prevention & control*
  • Ceftriaxone / administration & dosage
  • Ceftriaxone / pharmacology*
  • Colony Count, Microbial
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Bacterial
  • Enterococcus faecium / drug effects*
  • Feces / microbiology
  • Female
  • Gastrointestinal Tract / microbiology
  • Gram-Positive Bacterial Infections / prevention & control
  • Mice
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology*
  • Piperacillin / administration & dosage
  • Piperacillin / pharmacology*
  • Piperacillin, Tazobactam Drug Combination

Substances

  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Ceftriaxone
  • Penicillanic Acid
  • Piperacillin