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Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" cystic fibrosis patients.

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@article{fda00194a13c41ed9b75653dc46838e4,
title = "Omics-based tracking of Pseudomonas aeruginosa persistence in {"}eradicated{"} cystic fibrosis patients.",
abstract = "Whenever Pseudomonas aeruginosa is cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by ≥6 months of negative bacterial airway cultures. However, we suspect that P. aeruginosa persists in airways without clinical detection for long periods.Out of 298 P. aeruginosa-infected Copenhagen CF patients, we identified 80 with complete P. aeruginosa monitoring records and measured their maximum P. aeruginosa-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.69 (86%) patients 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. 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 (n=15) showed MEPs adjacent to surgery, and only five 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 probably benefit from tailored antibiotic therapy. ",
keywords = "Anti-Bacterial Agents/therapeutic use, Cystic Fibrosis/drug therapy, Humans, Phylogeny, Pseudomonas Infections/drug therapy, Pseudomonas aeruginosa/genetics",
author = "Bartell, {Jennifer A} and Sommer, {Lea M} and Marvig, {Rasmus L} and Marianne Skov and Tacjana Pressler and S{\o}ren Molin and Johansen, {Helle Krogh}",
note = "Copyright {\textcopyright}ERS 2021.",
year = "2021",
month = apr,
doi = "10.1183/13993003.00512-2020",
language = "English",
volume = "57",
journal = "European Respiratory Journal",
issn = "0903-1936",
publisher = "European Respiratory Society",
number = "4",

}

RIS

TY - JOUR

T1 - Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" cystic fibrosis patients.

AU - Bartell, Jennifer A

AU - Sommer, Lea M

AU - Marvig, Rasmus L

AU - Skov, Marianne

AU - Pressler, Tacjana

AU - Molin, Søren

AU - Johansen, Helle Krogh

N1 - Copyright ©ERS 2021.

PY - 2021/4

Y1 - 2021/4

N2 - Whenever Pseudomonas aeruginosa is cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by ≥6 months of negative bacterial airway cultures. However, we suspect that P. aeruginosa persists in airways without clinical detection for long periods.Out of 298 P. aeruginosa-infected Copenhagen CF patients, we identified 80 with complete P. aeruginosa monitoring records and measured their maximum P. aeruginosa-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.69 (86%) patients 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. 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 (n=15) showed MEPs adjacent to surgery, and only five 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 probably benefit from tailored antibiotic therapy.

AB - Whenever Pseudomonas aeruginosa is cultured from cystic fibrosis (CF) patient airways, the primary goal is eradication by antibiotic therapy. Success is defined by ≥6 months of negative bacterial airway cultures. However, we suspect that P. aeruginosa persists in airways without clinical detection for long periods.Out of 298 P. aeruginosa-infected Copenhagen CF patients, we identified 80 with complete P. aeruginosa monitoring records and measured their maximum P. aeruginosa-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.69 (86%) patients 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. 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 (n=15) showed MEPs adjacent to surgery, and only five 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 probably benefit from tailored antibiotic therapy.

KW - Anti-Bacterial Agents/therapeutic use

KW - Cystic Fibrosis/drug therapy

KW - Humans

KW - Phylogeny

KW - Pseudomonas Infections/drug therapy

KW - Pseudomonas aeruginosa/genetics

UR - http://www.scopus.com/inward/record.url?scp=85097757915&partnerID=8YFLogxK

U2 - 10.1183/13993003.00512-2020

DO - 10.1183/13993003.00512-2020

M3 - Journal article

C2 - 33093121

VL - 57

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 4

M1 - 2000512

ER -

ID: 62033538