Pooling isolates to address the diversity in antimicrobial susceptibility of Pseudomonas aeruginosa in cystic fibrosis.

IMPORTANCE: People with cystic fibrosis (pwCF) often suffer from chronic lung infections with Pseudomonas aeruginosa. While antibiotics are still commonly used to treat P. aeruginosa infections, there is a high discordance between in vitro and in vivo antibiotic efficacy, which contributes to suboptimal antibiotic therapy. In the present study, we found that isolates from the same sputum sample had highly diverse antibiotic resistance profiles [based on the minimal inhibitory concentration (MIC)], which may explain the reported discrepancy between in vitro and in vivo antibiotic efficacy. Through systematic analysis, we report that pooling nine isolates per sputum sample significantly decreased intrasample diversity in MIC and influenced clinical interpretation of antibiotic susceptibility tests compared to single isolate testing. Hence, pooling of isolates may offer a solution to obtain a consistent MIC test result and could lead to optimizing antibiotic therapy in pwCF and other infectious diseases where diversity in antibiotic resistance is observed.

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

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.