EVALUATION OF CP-99,219, A NEW FLUOROQUINOLONE, FOR TREATMENT OF EXPERIMENTAL PENICILLIN-RESISTANT AND CEPHALOSPORIN-RESISTANT PNEUMOCOCCALMENINGITIS

CP-99,219 is a new fluoroquinolone that has excellent activity against gram-positive organisms including penicillin- and cephalosporin-resis tant Streptococcus pneumoniae strains, In our well-established rabbit model of meningitis, we conducted experiments to determine the concent rations of CP-99,219 in cerebrospinal fluid (CSF) after intravenous ad ministration and its ability to eradicate two penicillin-resistant pne umococcal isolates, The peak and trough concentrations of CP-99,219 in the CSF were from 19 to 25% of the concentrations simultaneously obta ined in serum and were unaffected by concomitant dexamethasone adminis tration. Compared with untreated (control) animals, three doses of CP- 99,219 given 5 h apart significantly reduced the bacterial count in CS F by 5 to 6 log(10) CFU at 10 h, Although 47% of the dexamethasone-tre ated animals and 18% of those not given the steroid had positive cultu res at 24 h (14 h after administration of the last antibiotic dose), t he mean bacterial counts did not change from those observed at 10 h, A dditionally, only results for animals infected with one of the two pne umococcal strains appeared to be affected by concomitant dexamethasone therapy.