Acquired resistance to macrolides in Pseudomonas aeruginosa from cystic fibrosis patients

[摘要] 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.

[学科分类] 呼吸医学