title: Evaluation of CP-99,219, a new fluoroquinolone, for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.
abstract: CP-99,219 is a new fluoroquinolone that has excellent activity against gram-positive organisms including penicillin- and cephalosporin-resistant Streptococcus pneumoniae strains. In our well-established rabbit model of meningitis, we conducted experiments to determine the concentrations of CP-99,219 in cerebrospinal fluid (CSF) after intravenous administration and its ability to eradicate two penicillin-resistant pneumococcal isolates. The peak and trough concentrations of CP-99,219 in the CSF were from 19 to 25% of the concentrations simultaneously obtained in serum and were unaffected by concomitant dexamethasone administration. Compared with untreated (control) animals, three doses of CP-99,219 given 5 h apart significantly reduced the bacterial count in CSF by 5 to 6 log10 CFU at 10 h. Although 47% of the dexamethasone-treated animals and 18% of those not given the steroid had positive cultures at 24 h (14 h after administration of the last antibiotic dose), the mean bacterial counts did not change from those observed at 10 h. Additionally, only results for animals infected with one of the two pneumococcal strains appeared to be affected by concomitant dexamethasone therapy.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: París
authors.forename: S M
authors.initials: SM
authors.lastname: Hickey
authors.forename: M
authors.initials: M
authors.lastname: Trujillo
authors.forename: S
authors.initials: S
authors.lastname: Shelton
authors.forename: G H
authors.initials: GH
authors.lastname: McCracken
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000494:pharmacology; D018550:Cephalosporin Resistance; D015169:Colony Count, Microbial; D003907:Dexamethasone / Q000494:pharmacology; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D010403:Penicillin Resistance; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D014640:Vancomycin; D002443:Ceftriaxone; D003907:Dexamethasone; C080163:trovafloxacin