A hollow fiber infection model to study intracellular and extracellular antibiotic activity against Staphylococcus aureus

Antibiotic activity against intracellular pathogens is commonly evaluated in static models that do not reproduce plasma concentration fluctuations. However, efficacy is influenced by exposure conditions, related to drug pharmacokinetic profile. This study developed and validated an intracellular pharmacodynamic model using the hollow fiber system, the gold standard for evaluating extracellular antibiotic activity. The activity of fluoroquinolones, i.e., bactericidal antibiotics with intracellular tropism, was studied against intracellular Staphylococcus aureus , involved in persistence/recurrence of infections. In this model, moxifloxacin was more effective than in static conditions (0.87 log 10 killing gain), while ciprofloxacin kill rate was slower (18 vs. 12 h to achieve 1 log 10 killing). These differences were linked to the Cmax/MIC ratio, which was 2.5-fold higher for moxifloxacin but 3.4-fold lower for ciprofloxacin in dynamic vs. static conditions. This model could be applied to other drugs, cell types, or pathogens, offering a tool for optimizing dosing schemes and considering intracellular reservoirs.