Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

Nicole Mayer-Hamblett, Richard A. Kronmal, Ronald L. Gibson, Margaret Rosenfeld, George Retsch-Bogart, Miriam Treggiari, Jane L. Burns, Umer Khan, Bonnie W. Ramsey

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Rationale The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown. Objectives To determine if failure of antibiotic therapy to eradicate Pa and frequency of Pa recurrence are associated with increased exacerbation risk. Methods The cohort included 282 children with CF who participated in the EPIC trial ages 1-12 with newly acquired Pa, defined as either a first lifetime Pa positive respiratory culture or positive after two years of negative cultures (past isolation of Pa but >2 years prior to the trial). All received antibiotics to promote initial eradication followed by 15 months of intermittent maintenance antibiotics. Quarterly cultures were used to define initial eradication success and subsequent number of Pa recurrences. A standardized symptom-based definition of exacerbation was utilized. Cox proportional hazards models were used to estimate exacerbation risk. Results Failure to initially eradicate Pa was associated with exacerbation risk (hazard ratio [HR]: 2.49, 95% confidence interval [CI] 1.26, 4.93). In 245/282 with successful initial eradication during the trial, past isolation of Pa >2 years before the trial was the most significant predictor of exacerbation (HR 1.62, 95% CI 1.12, 2.35). In 37/282 who failed initial eradication, persistent Pa during the maintenance phase (1 or more Pa recurrences after failure to initially eradicate) added even greater exacerbation risk (HR 4.13, 95% CI 1.28, 13.32). Conclusions Children with CF who fail to eradicate after initial antibiotic treatment are at higher risk of subsequent exacerbation, suggesting clinical benefit to successful early eradication of Pa infection.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalPediatric Pulmonology
Volume47
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

Fingerprint

Treatment Failure
Cystic Fibrosis
Pseudomonas aeruginosa
Anti-Bacterial Agents
Confidence Intervals
Recurrence
Odds Ratio
Maintenance
Pseudomonas Infections
Proportional Hazards Models
Lung

Keywords

  • clinical outcome
  • early intervention
  • eradication
  • new acquisition

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Mayer-Hamblett, N., Kronmal, R. A., Gibson, R. L., Rosenfeld, M., Retsch-Bogart, G., Treggiari, M., ... Ramsey, B. W. (2012). Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis. Pediatric Pulmonology, 47(2), 125-134. https://doi.org/10.1002/ppul.21525

Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis. / Mayer-Hamblett, Nicole; Kronmal, Richard A.; Gibson, Ronald L.; Rosenfeld, Margaret; Retsch-Bogart, George; Treggiari, Miriam; Burns, Jane L.; Khan, Umer; Ramsey, Bonnie W.

In: Pediatric Pulmonology, Vol. 47, No. 2, 02.2012, p. 125-134.

Research output: Contribution to journalArticle

Mayer-Hamblett, N, Kronmal, RA, Gibson, RL, Rosenfeld, M, Retsch-Bogart, G, Treggiari, M, Burns, JL, Khan, U & Ramsey, BW 2012, 'Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis', Pediatric Pulmonology, vol. 47, no. 2, pp. 125-134. https://doi.org/10.1002/ppul.21525
Mayer-Hamblett, Nicole ; Kronmal, Richard A. ; Gibson, Ronald L. ; Rosenfeld, Margaret ; Retsch-Bogart, George ; Treggiari, Miriam ; Burns, Jane L. ; Khan, Umer ; Ramsey, Bonnie W. / Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis. In: Pediatric Pulmonology. 2012 ; Vol. 47, No. 2. pp. 125-134.
@article{a56f5fc542404c0fb6ea3eb82d0a9dfa,
title = "Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis",
abstract = "Rationale The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown. Objectives To determine if failure of antibiotic therapy to eradicate Pa and frequency of Pa recurrence are associated with increased exacerbation risk. Methods The cohort included 282 children with CF who participated in the EPIC trial ages 1-12 with newly acquired Pa, defined as either a first lifetime Pa positive respiratory culture or positive after two years of negative cultures (past isolation of Pa but >2 years prior to the trial). All received antibiotics to promote initial eradication followed by 15 months of intermittent maintenance antibiotics. Quarterly cultures were used to define initial eradication success and subsequent number of Pa recurrences. A standardized symptom-based definition of exacerbation was utilized. Cox proportional hazards models were used to estimate exacerbation risk. Results Failure to initially eradicate Pa was associated with exacerbation risk (hazard ratio [HR]: 2.49, 95{\%} confidence interval [CI] 1.26, 4.93). In 245/282 with successful initial eradication during the trial, past isolation of Pa >2 years before the trial was the most significant predictor of exacerbation (HR 1.62, 95{\%} CI 1.12, 2.35). In 37/282 who failed initial eradication, persistent Pa during the maintenance phase (1 or more Pa recurrences after failure to initially eradicate) added even greater exacerbation risk (HR 4.13, 95{\%} CI 1.28, 13.32). Conclusions Children with CF who fail to eradicate after initial antibiotic treatment are at higher risk of subsequent exacerbation, suggesting clinical benefit to successful early eradication of Pa infection.",
keywords = "clinical outcome, early intervention, eradication, new acquisition",
author = "Nicole Mayer-Hamblett and Kronmal, {Richard A.} and Gibson, {Ronald L.} and Margaret Rosenfeld and George Retsch-Bogart and Miriam Treggiari and Burns, {Jane L.} and Umer Khan and Ramsey, {Bonnie W.}",
year = "2012",
month = "2",
doi = "10.1002/ppul.21525",
language = "English (US)",
volume = "47",
pages = "125--134",
journal = "Pediatric Pulmonology",
issn = "8755-6863",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

AU - Mayer-Hamblett, Nicole

AU - Kronmal, Richard A.

AU - Gibson, Ronald L.

AU - Rosenfeld, Margaret

AU - Retsch-Bogart, George

AU - Treggiari, Miriam

AU - Burns, Jane L.

AU - Khan, Umer

AU - Ramsey, Bonnie W.

PY - 2012/2

Y1 - 2012/2

N2 - Rationale The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown. Objectives To determine if failure of antibiotic therapy to eradicate Pa and frequency of Pa recurrence are associated with increased exacerbation risk. Methods The cohort included 282 children with CF who participated in the EPIC trial ages 1-12 with newly acquired Pa, defined as either a first lifetime Pa positive respiratory culture or positive after two years of negative cultures (past isolation of Pa but >2 years prior to the trial). All received antibiotics to promote initial eradication followed by 15 months of intermittent maintenance antibiotics. Quarterly cultures were used to define initial eradication success and subsequent number of Pa recurrences. A standardized symptom-based definition of exacerbation was utilized. Cox proportional hazards models were used to estimate exacerbation risk. Results Failure to initially eradicate Pa was associated with exacerbation risk (hazard ratio [HR]: 2.49, 95% confidence interval [CI] 1.26, 4.93). In 245/282 with successful initial eradication during the trial, past isolation of Pa >2 years before the trial was the most significant predictor of exacerbation (HR 1.62, 95% CI 1.12, 2.35). In 37/282 who failed initial eradication, persistent Pa during the maintenance phase (1 or more Pa recurrences after failure to initially eradicate) added even greater exacerbation risk (HR 4.13, 95% CI 1.28, 13.32). Conclusions Children with CF who fail to eradicate after initial antibiotic treatment are at higher risk of subsequent exacerbation, suggesting clinical benefit to successful early eradication of Pa infection.

AB - Rationale The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown. Objectives To determine if failure of antibiotic therapy to eradicate Pa and frequency of Pa recurrence are associated with increased exacerbation risk. Methods The cohort included 282 children with CF who participated in the EPIC trial ages 1-12 with newly acquired Pa, defined as either a first lifetime Pa positive respiratory culture or positive after two years of negative cultures (past isolation of Pa but >2 years prior to the trial). All received antibiotics to promote initial eradication followed by 15 months of intermittent maintenance antibiotics. Quarterly cultures were used to define initial eradication success and subsequent number of Pa recurrences. A standardized symptom-based definition of exacerbation was utilized. Cox proportional hazards models were used to estimate exacerbation risk. Results Failure to initially eradicate Pa was associated with exacerbation risk (hazard ratio [HR]: 2.49, 95% confidence interval [CI] 1.26, 4.93). In 245/282 with successful initial eradication during the trial, past isolation of Pa >2 years before the trial was the most significant predictor of exacerbation (HR 1.62, 95% CI 1.12, 2.35). In 37/282 who failed initial eradication, persistent Pa during the maintenance phase (1 or more Pa recurrences after failure to initially eradicate) added even greater exacerbation risk (HR 4.13, 95% CI 1.28, 13.32). Conclusions Children with CF who fail to eradicate after initial antibiotic treatment are at higher risk of subsequent exacerbation, suggesting clinical benefit to successful early eradication of Pa infection.

KW - clinical outcome

KW - early intervention

KW - eradication

KW - new acquisition

UR - http://www.scopus.com/inward/record.url?scp=84855892151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855892151&partnerID=8YFLogxK

U2 - 10.1002/ppul.21525

DO - 10.1002/ppul.21525

M3 - Article

VL - 47

SP - 125

EP - 134

JO - Pediatric Pulmonology

JF - Pediatric Pulmonology

SN - 8755-6863

IS - 2

ER -