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  • Title: Pharmacodynamic evaluation of tosufloxacin against Streptococcus pneumoniae in an in vitro model simulating serum concentration.
    Author: Fukuda Y, Takahata M, Mitsuyama J.
    Journal: J Infect Chemother; 2006 Feb; 12(1):1-8. PubMed ID: 16506083.
    Abstract:
    We compared the antibacterial effects and the emergence of resistance to tosufloxacin or levofloxacin for Streptococcus pneumoniae by simulating the serum concentration according to the Japanese clinical regimens using an in vitro pharmacokinetic-pharmacodynamic model. For quinolone-susceptible strain ATCC49619, tosufloxacin showed bactericidal activity, given that both the AUC(0-24h)/MIC ratios at the dosage of 150 mg t.i.d. and 300 mg b.i.d. of tosufloxacin tosilate were 138 and 193, and the C(max)/MIC ranges were 7.93-10.2 and 15.9-17.6, respectively, which were greater than those of levofloxacin (100 mg t.i.d. and 200 mg b.i.d.). The greater area above the killing curves (AAKCs) or shorter time to achieve 99.9% killing (99.9% KT) in both models of tosufloxacin than those of levofloxacin was related to their larger AUC(0-24h)/MIC and C(max)/MIC. Exposure of only 100 mg t.i.d. of levofloxacin led to outgrowth of the parC mutants, which were twofold less susceptible to levofloxacin than the parent strain. Neither of the tosufloxacin tosilate regimens resulted in isolation of resistant mutants of this strain. For the parC mutant strain D-3197, both the AUC(0-24h)/MIC and C(max)/MIC ratios of tosufloxacin were greater than those of levofloxacin, which resulted in comparable or better bactericidal activity as compared to those of levofloxacin. However, both fluoroquinolones and both regimens led to outgrowth of resistant mutants, which possessed a mutation in gyrA in addition to parC. In conclusion, tosufloxacin is superior to levofloxacin in bactericidal activity against S. pneumoniae in the Japanese clinical regimens, especially in the quinolone-susceptible strain, without emergence of resistant subpopulations.
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