Optimization of antibiotic inhalation therapy in Cystic Fibrosis : studies on nebulized tobramycin : development of a colistin dry powder inhaler system

Cystic Fibrosis (CF) is the most frequent lethal inherited disease in the white population. In CF patients, the pulmonary complications are responsible for the majority of morbidity and virtually all mortality. Life expectancy has improved dramatically over the last decades due to a higher efficacy of the antibiotic treatment but also due to improved mucolytic therapy, airway physiotherapy and improved nutritional strategies including the use of pancreatic enzyme preparations. Gene therapy is a promising new therapeutic strategy but not yet available and probably will not be for the majority of the adult patients in short time. The optimization of antibiotic treatment has been subject of research in our Cystic Fibrosis center for several years. To date, there is no consensus what strategy of antibiotic therapy is to be preferred. The inhalation of antibiotics seems an interesting option to reach the microorganisms in the airways. Limited efficacy of the inhalation of antibiotics and limited knowledge of the pharmacokinetics after inhalation provided a rationale for a number of studies described in this thesis. Nebulizers are the only devices currently used in CF to inhale antibiotics. A drawback of inhalation therapy with nebulizers is the low depostion efficiency of the drug in the airways. Furthermore, because it is time consuming, patient compliance is relatively low. Reasons why a dry powder inhaler, being a more efficient and convenient alternative, was developed and investigated. Zie: Summary.