Pharmacodynamics of Gatifloxacin in Experimental Models of Pneumococcal Meningitis

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Abstract
The alarming increase of bacterial resistance has had a serious impact on treatment practices for patients with meningitis and has prompted investigation of other possibly effective antibiotic regimens with agents, such as gatifloxacin and trovafloxacin, that have excellent activity against Streptococcus pneumoniae. The use of fluoroquinolones in children has been limited by studies that report chondrotoxicity in young animals. Gatifloxacin, a new fluoroquinolone, was recently tested in a rabbit model of cephalosporin-resistant pneumococcal meningitis. In these studies, animals were infected with a ceftriaxone-resistant (minimal inhibitory concentration [MIC], 4 µg/mL; minimal bactericidal concentration [MBC], 4 µg/mL) and gatifloxacin-susceptible (MIC, 0.125 µg/mL; MBC, 0.25 µg/mL) strain of S. pneumoniae and were treated with either a single- or divided-dose regimen of gatifloxacin. Results from these studies are reviewed and compared with data from other studies that used a similar rabbit model of pneumococcal meningitis. Overall, it was found that the bacteriologic efficacy of gatifloxacin against S. pneumoniae was as effective as that of conventional regimens. Bactericidal activity of gatifloxacin was correlated with the area under the time-concentration curve-to-MBC ratio; maximal activity was achieved when gatifloxacin concentrations exceeded the MBC for the entire dosing interval.