Pharmacodynamic modeling of in vitro activity of marbofloxacin against Escherichia coli strains.
Abstract
A mathematical pharmacodynamic model was developed to describe the bactericidal activity of marbofloxacin against Escherichia coli strains with reduced susceptibility levels (determined using MICs) under optimal and intestinal growth conditions. Model parameters were estimated using nonlinear least-square curve-fitting procedures for each E. coli strain. Parameters related to bactericidal activity were subsequently analyzed using a maximum-effect (E(max)) model adapted to account for a direct and a delayed effect. While net growth rates did not vary significantly with strain susceptibility, culture medium had a major effect. The bactericidal activity of marbofloxacin was closely associated with the concentration and the duration of exposure of the bacteria to the antimicrobial agent. The value of the concentration inducing a half-maximum effect (C(50)) was highly correlated with MIC values (R(2) = 0.87 and R(2) = 0.94 under intestinal and optimal conditions, respectively). Our model reproduced the time-kill kinetics with good accuracy (R(2) of >0.90) and helped explain observed regrowth.