The efficacy of trovafloxacin versus ceftriaxone in the treatment of experimental brain abscess/cerebritis in the rat.
Current estimates of the mortality associated with brain abscesses range from 0-24%, with neurological sequellae in 30-55% of survivors. Although the incidence of brain abscess appears to be increasing, likely due to an increase in the population of immunosuppressed patients, the condition is still sufficiently uncommon to make human clinical trials of therapy problematic. An animal model to study the efficacy of new treatment regimens, specifically, new antimicrobial agents is therefore necessary. This study uses a well-defined experimental paradigm as an inexpensive method of inducing and studying the efficacy of antibiotics in brain abscess. The rat model of brain abscess/cerebritis developed at this institution was used to determine the relative efficacy of trovafloxacin as compared to ceftriaxone in animals infected with Staphylococcus aureus. S. aureus ( approximately 10(5) CFU in 1 microliter) was injected with a Hamilton syringe, very slowly, over the course of 70 minutes after a two mm burr hole was created with a spherical carbide drill just posterior to the coronal suture and four mm lateral to the midline. Eighteen hours later treatment was begun; every 8 hours the rats were dosed with subcutaneous ceftriaxone (n = 10), trovafloxacin (n = 11) or 0.9% sterile pyogen-free saline (n = 10). After four days of treatment the brains were removed and sectioned with a scalpel. The entire injected hemisphere was homogenized and quantitative cultures performed. The mean +/- SEM log(10) colony forming units/ml S. aureus recovered from homogenized brain were as follows: controls 6.10 +/- 0.28; ceftriaxone 3.43 +/- 0.33; trovafloxacin 3.65 +/- 0.3. There was no significant difference in bacterial clearance between ceftriaxone versus trovafloxacin (p = 0.39). Trovafloxacin or other quinolones may provide a viable alternative to intravenous antibiotics in patients with brain abscess/cerebritis.
Nathan
Barnett R
BR
Departments of Neurology and Internal Medicine, University of Virginia, Box 800394, Charlottesville, VA 22908, USA. brn3a@virginia.edu
Scheld
W Michael
WM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D019540:Area Under Curve; D001922:Brain Abscess / Q000188:drug therapy* / Q000382:microbiology; D002443:Ceftriaxone / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D007279:Injections, Subcutaneous; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002443:Ceftriaxone; C080163:trovafloxacin