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Antimicrobial Agents and Chemotherapy, September 2004, p. 3343-3348, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3343-3348.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Novel Murine Model of Pneumococcal Pneumonia: Use of Temperature as a Measure of Disease Severity To Compare the Efficacies of Moxifloxacin and Levofloxacin

Toronto Centre for Antimicrobial Research and Evaluation (ToCARE),¹ Department of Microbiology,² Department of Pharmacy, Mount Sinai Hospital,⁵ Department of Laboratory Medicine and Pathobiology, Faculty of Medicine,³ Faculty of Pharmacy, University of Toronto,⁶ Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital,⁴ University Health Network, Toronto,⁷ Division of Infectious Diseases, McMaster University, Henderson Site, Hamilton Health Sciences Corporation, Hamilton, Canada⁸

Received 2 February 2004/ Returned for modification 4 March 2004/ Accepted 22 April 2004

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

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