In vivo postantibiotic effect in a thigh infection in neutropenic mice

J Infect Dis. 1988 Feb;157(2):287-98. doi: 10.1093/infdis/157.2.287.

Abstract

The postantibiotic effect (PAE) is the suppression of bacterial growth that persists after limited exposure of organisms to antimicrobial agents. We demonstrated and standardized the in vivo PAE in a thigh infection model in neutropenic mice. Inhibitors of protein and nucleic acid synthesis induced PAEs of 1.4-7.5 h against aerobic gram-negative bacilli, whereas beta-lactam antibiotics did not induce significant PAEs. Against aerobic gram-positive cocci, cell wall-active agents and inhibitors of protein and nucleic acid synthesis induced PAEs of 1.2-7.1 h, except for penicillins, which did not induce PAEs against streptococci. With few exceptions the in vivo PAE correlated well with the PAE reported in prior in vitro studies. Residual drug in thigh tissue did not cause the PAE. Theoretically, the presence of a PAE may allow antimicrobial agents to be given more intermittently without organism regrowth after drug levels fall below the minimal inhibitory concentration.

Publication types

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

MeSH terms

  • Agranulocytosis / complications*
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Infections / complications
  • Bacterial Infections / drug therapy*
  • Disease Models, Animal
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Female
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / growth & development
  • Mice
  • Neutropenia / complications*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / growth & development
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pyogenes / drug effects
  • Streptococcus pyogenes / growth & development
  • Thigh

Substances

  • Anti-Bacterial Agents