Pharmacodynamic evaluation of @entity26654 against XXXX in an in vitro model simulating serum concentration.

@entity2260 @entity26654 @entity2887 @entity800 @entity328 @entity1536
We compared the antibacterial effects and the emergence of resistance to @entity26654 or @entity800 for @entity328 by simulating the serum concentration according to the Japanese clinical regimens using an in vitro pharmacokinetic-pharmacodynamic model. For @entity1536 -susceptible strain ATCC49619, @entity26654 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 @entity26654 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 @entity800 (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 @entity26654 than those of @entity800 was related to their larger AUC(0-24h)/MIC and C(max)/MIC. Exposure of only 100 mg t.i.d. of @entity800 led to outgrowth of the parC mutants, which were twofold less susceptible to @entity800 than the parent strain. Neither of the @entity26654 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 @entity26654 were greater than those of @entity800 , which resulted in comparable or better bactericidal activity as compared to those of @entity800 . However, both @entity2887 and both regimens led to outgrowth of resistant mutants, which possessed a mutation in gyrA in addition to parC. In conclusion, @entity26654 is superior to @entity800 in bactericidal activity against @entity2260 in the Japanese clinical regimens, especially in the @entity1536 -susceptible strain, without emergence of resistant subpopulations.
