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

Trovafloxacin is a recently approved fluoroquinolone with excellent activit y against Gram-positive and Gram-negative organisms that offers a potential alternative for treatment of beta-lactam-resistant pneumococcal meningitis . Using the rabbit meningitis model, we sought to characterize the pharmaco dynamic properties of trovafloxacin in the cerebrospinal fluid (CSF). Anima ls 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 ra te increased with increasing dosages of trovafloxacin, indicating that its activity is concentration dependent. All three pharmacodynamic indices (are a under the concentration curve (AUC)/MBC, peak concentration (C-max)/MBC, and time above MBC (T > MBC)) correlated with bacterial killing; however, A UC/MBC correlated best (r = 0.71). In a second experiment we found comparab le bacterial killing with multiple doses of trovafloxacin given either ever y serum half-life or every two serum half-lives. In both experiments bacter ial regrowth occurred when the concentration of trovafloxacin in CSF fell b elow the MBC. These data have been used in formulating an appropriate regim en for trovafloxacin treatment of bacterial meningitis in children.