Pharmacodynamics of moxifloxacin, levofloxacin and sparfloxacin against Streptococcus pneumoniae
Abstract
An in vitro pharmacokinetic model (IVPM) was used to simulate the human serum pharmacokinetics of moxifloxacin, levofloxacin and sparfloxacin, and to compare their pharmacodynamics against Streptococcus pneumoniae exhibiting a wide range of susceptibilities to fluoroquinolones. Logarithmic-phase cultures were exposed to peak concentrations achieved in human serum of moxifloxacin, levofloxacin or sparfloxacin with oral doses of 400, 500 and 200 mg, respectively. Human elimination pharmacokinetics were simulated, and viable bacterial counts were measured at 0, 1, 2, 4, 6, 8, 24 and 36 h. Moxifloxacin was rapidly bactericidal (>3 logs of killing) against all 10 S. pneumoniae strains, with 99.9% kills of eight strains occurring within 1-3 h after dosing. Maximum kills ranged from 5 to >6 logs. Moxifloxacin eradicated seven strains from the IVPM within 8 h of the first dose, and eradicated two other strains within 24 h. Although levofloxacin and sparfloxacin were also bactericidal against all 10 S. pneumoniae strains, the rates of killing were somewhat slower, with sparfloxacin exhibiting the slowest rate of kill. In summary, moxifloxacin's increased anti-pneumococcal potency compared with levofloxacin and its more favourable pharmacokinetics compared with sparfloxacin provided enhanced pharmacodynamic activity against some S. pneumoniae strains when maximum doses were simulated in an IVPM.
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