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Chronic airway colonisation by  Pseudomonas aeruginosa , a hallmark of cystic fibrosis (CF) lung disease, is associated with increased morbidity and mortality and despite aggressive antibiotic treatment,  P. aeruginosa  is able to persist in CF airways.  In vitro  antibiotic susceptibility assays are poor predictors of antibiotic efficacy to treat respiratory tract infections in the CF patient population and the selection of the antibiotic(s) is often made on an empirical base. In the current review, we discuss the factors that are responsible for the discrepancies between antibiotic activity  in vitro  and clinical efficacy  in vivo . We describe how the CF lung microenvironment, shaped by host factors (such as iron, mucus, immune mediators and oxygen availability) and the microbiota, influences antibiotic activity and varies widely between patients. A better understanding of the CF microenvironment and population diversity may thus help improve  in vitro  antibiotic susceptibility testing and clinical decision making, in turn increasing the success rate of antibiotic treatment.

The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects