Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Jun;39(6):1243–1246. doi: 10.1128/aac.39.6.1243

Evaluation of CP-99,219, a new fluoroquinolone, for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

M M París 1, S M Hickey 1, M Trujillo 1, S Shelton 1, G H McCracken Jr 1
PMCID: PMC162720  PMID: 7574509

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.

Full Text

The Full Text of this article is available as a PDF (241.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dacey R. G., Sande M. A. Effect of probenecid on cerebrospinal fluid concentrations of penicillin and cephalosporin derivatives. Antimicrob Agents Chemother. 1974 Oct;6(4):437–441. doi: 10.1128/aac.6.4.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Del Rio M., McCracken G. H., Jr, Nelson J. D., Chrane D., Shelton S. Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis. Antimicrob Agents Chemother. 1982 Oct;22(4):622–627. doi: 10.1128/aac.22.4.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Eliopoulos G. M., Klimm K., Eliopoulos C. T., Ferraro M. J., Moellering R. C., Jr In vitro activity of CP-99,219, a new fluoroquinolone, against clinical isolates of gram-positive bacteria. Antimicrob Agents Chemother. 1993 Feb;37(2):366–370. doi: 10.1128/aac.37.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Friedland I. R., Paris M., Ehrett S., Hickey S., Olsen K., McCracken G. H., Jr Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother. 1993 Aug;37(8):1630–1636. doi: 10.1128/aac.37.8.1630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Friedland I. R., Shelton S., Paris M., Rinderknecht S., Ehrett S., Krisher K., McCracken G. H., Jr Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J. 1993 Mar;12(3):196–200. doi: 10.1097/00006454-199303000-00004. [DOI] [PubMed] [Google Scholar]
  6. Gooding B. B., Jones R. N. In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone. Antimicrob Agents Chemother. 1993 Feb;37(2):349–353. doi: 10.1128/aac.37.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jafari H. S., Sáez-Llorens X., Ramilo O., Shelton S. L., McCracken G. H., Jr Pharmacokinetics and antibacterial efficacy of cefpirome (HR 810) in experimental Escherichia coli and Haemophilus influenzae type b meningitis. Antimicrob Agents Chemother. 1991 Feb;35(2):220–223. doi: 10.1128/aac.35.2.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mustafa M. M., Ramilo O., Mertsola J., Risser R. C., Beutler B., Hansen E. J., McCracken G. H., Jr Modulation of inflammation and cachectin activity in relation to treatment of experimental Hemophilus influenzae type b meningitis. J Infect Dis. 1989 Nov;160(5):818–825. doi: 10.1093/infdis/160.5.818. [DOI] [PubMed] [Google Scholar]
  9. Odio C. M., Faingezicht I., Salas J. L., Guevara J., Mohs E., McCracken G. H., Jr Cefotaxime vs. conventional therapy for the treatment of bacterial meningitis of infants and children. Pediatr Infect Dis. 1986 Jul-Aug;5(4):402–407. doi: 10.1097/00006454-198607000-00005. [DOI] [PubMed] [Google Scholar]
  10. París M. M., Hickey S. M., Uscher M. I., Shelton S., Olsen K. D., McCracken G. H., Jr Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother. 1994 Jun;38(6):1320–1324. doi: 10.1128/aac.38.6.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Schaad U. B., McCracken G. H., Jr, Loock C. A., Thomas M. L. Pharmacokinetics and bacteriologic efficacy of moxalactam, cefotaxime, cefoperazone, and rocephin in experimental bacterial meningitis. J Infect Dis. 1981 Feb;143(2):156–163. doi: 10.1093/infdis/143.2.156. [DOI] [PubMed] [Google Scholar]
  12. Simon H. J., Yin E. J. Microbioassay of antimicrobial agents. Appl Microbiol. 1970 Apr;19(4):573–579. doi: 10.1128/am.19.4.573-579.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Syrogiannopoulos G. A., Hansen E. J., Erwin A. L., Munford R. S., Rutledge J., Reisch J. S., McCracken G. H., Jr Haemophilus influenzae type b lipooligosaccharide induces meningeal inflammation. J Infect Dis. 1988 Feb;157(2):237–244. doi: 10.1093/infdis/157.2.237. [DOI] [PubMed] [Google Scholar]
  14. Täuber M. G., Zak O., Scheld W. M., Hengstler B., Sande M. A. The postantibiotic effect in the treatment of experimental meningitis caused by Streptococcus pneumoniae in rabbits. J Infect Dis. 1984 Apr;149(4):575–583. doi: 10.1093/infdis/149.4.575. [DOI] [PubMed] [Google Scholar]
  15. del Rio M. A., Chrane D., Shelton S., McCracken G. H., Jr, Nelson J. D. Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children. Lancet. 1983 Jun 4;1(8336):1241–1244. doi: 10.1016/s0140-6736(83)92696-x. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES