Pseudomonas aeruginosa chronic infections in patients with bronchiectasis: a silent reservoir of carbapenemase-producing epidemic high-risk clones

Abstract

Objectives: Pseudomonas aeruginosa is one of the major drivers of morbidity and mortality in patients with chronic underlying diseases. Whereas cystic fibrosis (CF) P. aeruginosa strains have been well studied, non-CF bronchiectasis isolates have received less scientific attention.

Methods: We determined the antibiotic susceptibility profiles of a collection of 100 P. aeruginosa isolates recovered from a total of 100 non-CF bronchiectasis patients attending a Catalonian hospital. All carbapenemase-producing isolates were characterized by WGS.

Results: Twelve isolates were classified as MDR (12%) and six were found to be carbapenemase (VIM-2) producers (6%). Of note, two of the VIM-2-producing isolates were carbapenem susceptible due to the presence of inactivating mutations in MexAB-OprM efflux pump components. These isolates exhibited properties of chronic P. aeruginosa isolates, such as mutator or mucoid phenotypes that are associated with persistent infections despite intensive antibiotic therapies. The phylogenetic analysis evidenced that all VIM-2 isolates belonged to the high-risk clone ST235. Core-genome MLST analysis revealed 7-260 allelic differences, arguing against recent transmission but a common source of infection or an ancient interpatient transmission event could not be ruled out.

Conclusions: Altogether, these findings suggest that P. aeruginosa chronic respiratory infections can be an important and silent reservoir of transferable resistance determinants and P. aeruginosa high-risk clones, thus contributing to their increased resistance and worldwide dissemination.

Figure 1.

Antibiotic susceptibility profiles, isolate-specific resistome mutations and genetic relatedness of the VIM-2-producing isolates. FEP, cefepime (S ≤ 0.001; R > 8); TZP, piperacillin/tazobactam (S ≤ 0.001; R > 16); CAZ, ceftazidime (S ≤ 0.001; R > 8); ATM, aztreonam (S ≤ 0.001; R > 16); IPM, imipenem (S ≤ 0.001; R > 4); MEM, meropenem (S ≤ 2; R > 8); C/T, ceftolozane/tazobactam (S ≤ 4; R > 4); CZA, ceftazidime/avibactam (S ≤ 8; R > 8); IMR, imipenem/relebactam (S ≤ 2; R > 2); MEV, meropenem/vaborbactam (S ≤ 8; R > 8); FDC, cefiderocol (S ≤ 2; R > 2); CIP, ciprofloxacin (S ≤ 0.001; R > 0.5); TOB, tobramycin (S ≤ 2; R > 2); AMK, amikacin (S ≤ 16; R > 16); CST, colistin (S ≤ 4; R > 4). Green colour indicates clinical susceptibility at standard and increased dosing, while red indicates resistance.