Activity of moxifloxacin, administered once a day, against Streptococcus pneumoniae in an in vitro pharmacodynamic model of infection

Abstract

The antibacterial effect of moxifloxacin was studied by using an in vitro pharmacodynamic model of infection with dosing simulations of 400 mg every 24 h for 48 h. Streptococcus pneumoniae was tested by using four wild- type strains for which the moxifloxacin MICs were 0.008, 0.12, 0.14, and 3.6 mg/liter. In addition, two isogenic mutants, generated from the strains for which the moxifloxacin MICs were ≤0.12 mg/liter and for which the MICs were 1.0 and 1.6 mg/liter, were also used. Antibacterial efficacy was measured by the following indices: log change in viable count at 12, 24, 36, and 48 h; area under the bacterial kill curve (AUBKC); and time to kill 99.9% of the initial inoculum. With the three strains for which the moxifloxacin MICs were ≤0.14 mg/liter, there was a marked reduction in viable count over 12 to 36 h; in contrast, with strains for which the MICs were ≥1.0 mg/liter, little killing occurred over 48 h. A sigmoid dose-response model indicated that the area under the curve/MIC ratio was strongly related to the log change in viable count at 24 and 48 h and to the AUBKC. These data indicate that moxifloxacin may have a role in management of S. pneumoniae infection.