Activity of moxifloxacin against Bacteroides fragilis and Escherichia coli in an in vitro pharmacokinetic/pharmacodynamic model employing pure and mixed cultures

Abstract

The objective of this study was to determine the pharmacodynamic (PD) activity of moxifloxacin against four selected Bacteroides fragilis strains (three strains with low MICs and one strain with a high MIC) and two Escherichia coli strains (one strain with a low MIC and one strain with a high MIC) in a pharmacokinetic (PK) in vitro model in pure cultures as well as in mixed cultures. PK/PD assays of moxifloxacin were carried out with an initial maximum concentration of 4 . 0 mg l À1 and a half-life of 13 h. The E. coli strain with the low MIC was rapidly killed in both pure and mixed cultures in the in vitro PK/PD model, while the E. coli strain with the high MIC was not killed. None of the B. fragilis strains were rapidly killed in pure or mixed cultures. The bacterial numbers of the B. fragilis strains with low MICs were reduced by about one to two logs after 12 h in pure cultures. The presence of an E. coli strain with a low or a high MIC in the mixed culture reduced this effect even further.

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

“…Throughout 24 h simulation, the predicted concentration of moxifloacin in abdominal viscera exceeded the in vitro MICs of moxifloxacin for the pathogens commonly isolated in intra-abdominal infections, which have been reported as ≤1 μg/mL for a variety of Gram-negative and Gram-positive organisms [32]. In our study, moxifloxacin achieved high concentrations in abdominal viscera (liver 11.81 μg/mL; kidney 12.53 μg/mL; spleen 10.43 μg/mL), which indicated that it could play a good antibacterial activity in the abdominal cavity and that was in accordance with moxifloxacin clinical use in the treatment of intra-abdominal infection and was supported by the finding that moxifloxacin was effective in an in vitro pharmacokinetic-pharmacodynamic model with mixed aerobic (E. coli) and anaerobic (B. fragilis) strains [33].…”

Fluoroquinolones and Anaerobes

“…Bactericidal effects are observed against most anaerobic pathogens by 24-48 h at concentrations that are 2-4 times their respective MIC [25,40,41]. In mixed cultures of B. fragilis with Escherichia coli or Enterococcus faecium, the bactericidal activity of trovafloxacin and moxifloxacin against B. fragilis was found to be diminished, compared with the activity of these fluoroquinolones against pure cultures of B. fragilis [42,43].…”

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

“…Throughout 24 h simulation, the predicted concentration of moxifloacin in abdominal viscera exceeded the in vitro MICs of moxifloxacin for the pathogens commonly isolated in intra-abdominal infections, which have been reported as ≤1 µg/mL for a variety of Gram-negative and Gram-positive organisms [32]. In our study, moxifloxacin achieved high concentrations in abdominal viscera (liver 11.81 µg/mL; kidney 12.53 µg/mL; spleen 10.43 µg/mL), which indicated that it could play a good antibacterial activity in the abdominal cavity and that was in accordance with moxifloxacin clinical use in the treatment of intra-abdominal infection and was supported by the finding that moxifloxacin was effective in an in vitro pharmacokinetic-pharmacodynamic model with mixed aerobic ( E. coli ) and anaerobic ( B. fragilis ) strains [33]. …”