Acquired resistance to macrolides in Pseudomonas aeruginosa from cystic fibrosis patients. Issue 5 (19th May 2017)

• Record Type: Journal Article
• Authors: Mustafa, Muhammad-Hariri; Khandekar, Shaunak; Tunney, Michael M.; Elborn, J. Stuart; Kahl, Barbara C.; Denis, Olivier; Plésiat, Patrick; Traore, Hamidou; Tulkens, Paul M.; Vanderbist, Francis; Van Bambeke, Françoise
• Is Part Of: European respiratory journal. Volume 49:Issue 5(2017)
• Publication Date: 2017-05-19
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.01847-2016
• Languages: English
• ISSNs: 0903-1936

Abstract

Cystic fibrosis (CF) patients receive chronic treatment with macrolides for their antivirulence and anti-inflammatory properties. We, however, previously showed that Pseudomonas aeruginosa, considered as naturally resistant to macrolides, becomes susceptible when tested in a eukaryotic medium rather than a conventional broth. We therefore looked for specific macrolide resistance determinants in 333 CF isolates from four European CF centres in comparison with 48 isolates from patients suffering from hospital-acquired pneumonia (HAP). Minimum inhibitory concentrations (MICs) of macrolides and ketolides measured in eukaryotic medium (RPMI-1640) were higher towards CF than HAP isolates. Gene sequencing revealed mutations at three positions (2045, 2046 and 2598) in domain V of 23S rRNA of 43% of sequenced CF isolates, but none in HAP isolates. Enzymes degrading extracellular polymeric substances also reduced MICs, highlighting a role of the mucoid, biofilm-forming phenotype in resistance. An association between high MICs and chronic azithromycin administration was evidenced, which was statistically significant for patients infected by the Liverpool Epidemic Strain. Thus, ribosomal mutations are highly prevalent in CF isolates and may spread in epidemic clones, arguing for prudent use of oral macrolides in these patients. Measuring MICs in RPMI-1640 could be easily implemented in microbiology laboratories to phenotypically detect resistance. Ribosomal mutations are frequent in P. aeruginosa from cystic fibrosis patients, owing to chronic oral macrolide use http://ow.ly/B5vC308qfjl