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

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 30degreesC or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of less than or equal to 30degreesC 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 greater than or equal to 32degreesC) at the start of treatment had better clinical and bacteriological outcomes than mice assessed as severely ill (temperature < 32degreesC). 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.