Novel murine model of pneumococcal pneumonia: use of temperature as a measure of disease severity to compare the efficacies of moxifloxacin and levofloxacin

Antimicrob Agents Chemother. 2004 Sep;48(9):3343-8. doi: 10.1128/AAC.48.9.3343-3348.2004.

Abstract

Surface temperature measured by an infrared temperature-scanning thermometer was used to evaluate disease severity and predict imminent death in a murine model of pneumococcal pneumonia. We showed that a decrease in temperature was associated with increasing severity of disease and concomitant histological changes and also that a temperature of 30 degrees C or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of < or = 30 degrees C were not significantly different from those seen in the lungs of mice allowed to die without intervention. These data support temperature change as a more subtle indicator of outcome than death and demonstrate that this could be used as a reliable end point for euthanasia. To test the utility of our model in a drug trial, we examined the efficacies of moxifloxacin and levofloxacin by using temperature as a measure of disease severity prior to and during treatment. Regardless of the antibiotic used, mice assessed as moderately ill (temperature > or = 32 degrees C) at the start of treatment had better clinical and bacteriological outcomes than mice assessed as severely ill (temperature < 32 degrees C). However, moxifloxacin offered better protection and greater bacterial clearance than did levofloxacin in all infected mice independent of disease severity. This model not only allows a more subtle evaluation of drug efficacy but also ensures a better degree of standardization and a more humane approach to drug efficacy studies involving animals.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Aza Compounds / pharmacokinetics
  • Aza Compounds / therapeutic use*
  • Body Temperature / physiology*
  • Colony Count, Microbial
  • Disease Models, Animal
  • Female
  • Fluoroquinolones
  • Levofloxacin*
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Moxifloxacin
  • Ofloxacin / therapeutic use*
  • Pneumonia, Pneumococcal / drug therapy*
  • Pneumonia, Pneumococcal / physiopathology*
  • Quinolines / pharmacokinetics
  • Quinolines / therapeutic use*
  • Skin Temperature / physiology

Substances

  • Anti-Bacterial Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Levofloxacin
  • Ofloxacin
  • Moxifloxacin