PT  - JOURNAL ARTICLE
AU  - Jennifer A. Bartell
AU  - Lea M. Sommer
AU  - Rasmus L. Marvig
AU  - Marianne Skov
AU  - Tacjana Pressler
AU  - Søren Molin
AU  - Helle Krogh Johansen
TI  - Omics-based tracking of <em>Pseudomonas aeruginosa</em> persistence in “eradicated” CF patients
AID  - 10.1183/13993003.00512-2020
DP  - 2020 Jan 01
TA  - European Respiratory Journal
PG  - 2000512
4099  - http://erj.ersjournals.com/content/early/2020/10/15/13993003.00512-2020.short
4100  - http://erj.ersjournals.com/content/early/2020/10/15/13993003.00512-2020.full
AB  - 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;.Conflict of interest: Dr. Bartell reports grants from Cystic Fibrosis Foundation (grant number BARTEL18F0), during the conduct of the study;.Conflict of interest: Dr. Sommer has nothing to disclose.Conflict of interest: Dr. Marvig reports grants from Danish National Research Foundation (grant number 126), during the conduct of the study;.Conflict of interest: Dr. Skov has nothing to disclose.Conflict of interest: Dr. Pressler has nothing to disclose.Conflict of interest: Dr. Molin reports grants from Cystic Fibrosis Foundation (grant# MOLIN18G0), during the conduct of the study;.Conflict of interest: Dr. Johansen has nothing to disclose.