Pharmacodynamics of trovafloxacin in experimental pneumococcal meningitis: Basis for dosage selection in children with meningitis

Cynthia C. McCoig, Loretta Wubbel, Hasan S. Jafri, Irja Lutsar, Rafael Bastero, Kurt Olsen, Sharon Shelton, Ian R. Friedland, George H. McCracken

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Trovafloxacin is a recently approved fluoroquinolone with excellent activity against Grampositive and Gram-negative organisms that offers a potential alternative for treatment of β-lactam-resistant pneumococcal meningitis. Using the rabbit meningitis model, we sought to characterize the pharmacodynamic properties of trovafloxacin in the cerebrospinal fluid (CSF). Animals were given single doses of trovafloxacin of 10, 15, 20 or 30 mg/kg; 1 h after infusion mean CSF concentrations were 0.59 ± 0.18, 0.74 ± 0.14, 1.12 ± 0.12 and 1.07 ± 0.35 mg/L, respectively. The bacterial killing rate increased with increasing dosages of trovafloxacin, indicating that its activity is concentration dependent. All three pharmacodynamic indices (area under the concentration curve (AUC)/MBC, peak concentration (C(max))/MBC, and time above MBC (T > MBC)) correlated with bacterial killing; however, AUC/MBC correlated best (r = 0.71). In a second experiment we found comparable bacterial killing with multiple doses of trovafloxacin given either every serum half-life or every two serum half-lives. In both experiments bacterial regrowth occurred when the concentration of trovafloxacin in CSF fell below the MBC. These data have been used in formulating an appropriate regimen for trovafloxacin treatment of bacterial meningitis in children.

Original languageEnglish (US)
Pages (from-to)683-688
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume43
Issue number5
DOIs
StatePublished - May 27 1999

    Fingerprint

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this