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 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.
Toronto Centre for Antimicrobial Research and Evaluation, Room 1483, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada. dbast@mtsinai.on.ca
Darrin J
DJ
Bast
M
M
Yue
X
X
Chen
D
D
Bell
L
L
Dresser
R
R
Saskin
L A
LA
Mandell
D E
DE
Low
Joyce C S
JC
de Azavedo
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001372:Aza Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001831:Body Temperature / Q000502:physiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D024841:Fluoroquinolones; D064704:Levofloxacin; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000503:physiopathology*; D011804:Quinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012881:Skin Temperature / Q000502:physiology
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin