Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" CF patients

Jennifer A Bartell, Lea M Sommer, Rasmus Lykke Marvig, Marianne Skov, Tacjana Pressler, Søren Molin, Helle Krogh Johansen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Whenever Pseudomonas aeruginosa (PA) is cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by at least 6 months of negative bacterial airway cultures. However, we suspect that PA persists in airways without clinical detection for long periods.Of 298 PA-infected Copenhagen CF patients, we identified 80 with complete PA monitoring records and measured their maximum PA-free eradication periods (MEP). Isolates from 72 patients were whole genome sequenced (n=567) and clone typed. Select isolate relatedness was examined through phylogenetic analysis and phenotypic multivariate modelling.Sixty-nine patients (86%) exhibited eradication in the monitoring period (2002-2018). Sequenced isolates bridged the MEP of 42 patients, and the same clone type persisted over the MEP in 18 (43%). Patients with failed eradication were on average treated more intensively with antibiotics, but this may be linked to their more severe pre-MEP infection trajectories. Of the 42 patients, 26 also had sinus surgery; the majority (15) show MEPs adjacent to surgery, and only 5 had persisting clone types. Importantly, combined phylogenetic-phenomic evaluation suggests that persisting clone types are a result of re-emergence of the same strain rather than re-infection from the environment, and similar relatedness is exhibited by paired lower and upper airway samples and in transmission cases.In conclusion, nearly half of CF patients with supposed eradication may not truly be cleared of their original bacteria according to omics-based monitoring. This distinct cohort that is persistently infected would likely benefit from tailored antibiotic therapy.
Original languageEnglish
Article number2000512
JournalThe European Respiratory Journal
Volume57
Issue number1
ISSN0903-1936
DOIs
Publication statusPublished - 2020

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