Mechanism-based modelling of antibiotic effects on Pseudomonas strains with different resistance mechanisms

Background: Pseudomonas aeruginosa has a large armamentarium of resistance mechanisms, enabling resistance emergence against almost all antibiotics in monotherapy. Alternative treatment options are required. Aims: To evaluate regimens of meropenem (MER) and ciprofloxacin (CIP), alone and combined, against isogenic P. aeruginosa strains with different resistance mechanisms in a dynamic hollow fibre infection model (HFIM) and […]

Effect of ciprofloxacin against Pseudomonas aeruginosa with different resistance mechanisms can be predicted with mechanism-based mathematical modelling where using PK/PD indices fails

Introduction: Pseudomonas aeruginosa has a large armamentarium of mutational resistance mechanisms enabling resistance emergence during therapy against almost all antibiotics. PK/PD indices are based on minimum inhibitory concentrations (MICs) and link bacterial response to antibiotic exposure. The index relevant for fluoroquinolone antibiotics is the ratio of free drug area under the concentration-time curve to MIC […]