TY - JOUR
T1 - Pharmacodynamics of trovafloxacin in experimental pneumococcal meningitis
T2 - Basis for dosage selection in children with meningitis
AU - McCoig, Cynthia C.
AU - Wubbel, Loretta
AU - Jafri, Hasan S.
AU - Lutsar, Irja
AU - Bastero, Rafael
AU - Olsen, Kurt
AU - Shelton, Sharon
AU - Friedland, Ian R.
AU - McCracken, George H.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1093/jac/43.5.683
DO - 10.1093/jac/43.5.683
M3 - Article
C2 - 10382890
AN - SCOPUS:0032942593
SN - 0305-7453
VL - 43
SP - 683
EP - 688
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 5
ER -