Which antibiotic can be used to treat lung biofilms by inhalation? A biopharmaceutical approach

Abstract zum Vortrag

In the lungs of patients with cystic fibrosis, biofilms of Pseudomonas aeruginosa are responsible for chronic infections that cannot be cured by conventional antibiotic (ATB) treatments. Indeed, bacteria in a biofilm are 100 to 1000 less sensitive to antibiotics than planktonic bacteria. Therefore, much higher concentrations of ATB than for the treatment of infections due to bacteria living in the planktonic form must be achieved near biofilms to be effective. In the lungs, such a high concentration of ATB can only be achieved without systemic toxicity to the patient by inhaling aerosols of ATB.  Indeed, pulmonary administration of ATB is a promising strategy for treating pulmonary infectious diseases because it allows a high local concentration and low systemic side effects. This is especially true for low permeability ATBs such as tobramycin or colistin, which penetrate the lungs at a low rate after systemic administration and benefit greatly from pulmonary administration in terms of local drug concentration. However, for relatively high permeable ATBs such as fluoroquinolones (FQ), the rate of absorption is so high that pulmonary administration has no therapeutic advantage over systemic or oral administration. Formulation strategies were then developed to decrease the rate of absorption and increase the residence time of FQs in the lung after inhalation. These strategies, which consist of either reducing the FQs permeability through the pulmonary epithelium or decreasing the rate of release of FQs in the epithelial lining fluid after pulmonary deposition, will be discussed.