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CME

MRSA in Patients With Cystic Fibrosis Linked to Shorter Survival Time

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Hien T. Nghiem, MD
  • CME Released: 6/16/2010
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 6/16/2011
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Target Audience and Goal Statement

This article is intended for primary care clinicians, pulmonologists, infectious disease specialists, and other specialists who care for patients with cystic fibrosis.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Report the most common cause of death in cystic fibrosis.
  2. Report the association between methicillin-resistant Staphylococcus aureus and survival duration in cystic fibrosis.


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Author(s)

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor(s)

  • Brande Nicole Martin

    CME Clinical Editor, Medscape, LLC

    Disclosures

    Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.

CME Author(s)

  • Hien T. Nghiem, MD

    Assistant Clinical Professor, Associate Residency Program Director, University of California, Irvine-Orange, Department of Family Medicine

    Disclosures

    Disclosure: Hien T. Nghiem, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC

    Disclosures

    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.


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CME

MRSA in Patients With Cystic Fibrosis Linked to Shorter Survival Time

Authors: News Author: Laurie Barclay, MD CME Author: Hien T. Nghiem, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME Released: 6/16/2010

Valid for credit through: 6/16/2011

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June 16, 2010 — Detection of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of patients with cystic fibrosis (CF) is associated with shorter survival duration, according to the results of a large cohort study reported in the June 16 issue of the Journal of the American Medical Association.

"The prevalence of ...MRSA in the respiratory tract of individuals with ...CF has increased dramatically; however, its impact on outcomes in CF is unclear," write Elliott C. Dasenbrook, MD, MHS, from Case Western Reserve University School of Medicine and University Hospitals Case Medical Center in Cleveland, Ohio, and colleagues. "Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge."

The goal of the study was to compare survival times in patients with CF in whom MRSA was detected in the respiratory tract with that in such patients who never had a culture result positive for MRSA. At US centers accredited by the Cystic Fibrosis Foundation, 19,833 patients aged 6 to 45 years were enrolled between January 1996 and December 2006 and were followed up through December 2008.

The investigators compared survival times between patients with CF with and without respiratory tract MRSA using Cox regression models with time-varying covariates. The main study endpoint was time from age at study enrollment to age at death from any cause.

There were 2537 deaths in 137,819 patient-years of observation (median, 7.3 years/patient). During that time, MRSA was detected in 5759 patients. Mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5 - 19.1) per 1000 patient-years in patients without MRSA vs 27.7 deaths (95% CI, 25.3 - 30.4) per 1000 patient-years in those with MRSA.

For patients in whom MRSA was detected, there was a 34.0% attributable risk of death associated with MRSA (95% CI, 26.7% - 40.4%). The unadjusted hazard ratio (HR) for death associated with MRSA was 1.47 (95% CI, 1.32 - 1.62), and HR remained significant after adjustment for time-varying covariates associated with severity of illness (HR, 1.27; 95% CI, 1.11 - 1.45).

"Detection of MRSA in the respiratory tract of CF patients was associated with worse survival," the study authors write.

Limitations of this study include possible misclassification of individuals within the study cohort, possible sampling bias resulting in an apparent increased association between survival time and MRSA, loss of more patients to follow-up in the MRSA-negative group, lack of detailed information on MRSA treatment, and possible unmeasured confounders because of the observational design.

"The results of this study in conjunction with previous data further establish MRSA as a significant CF pathogen and provide impetus for more aggressive treatment of CF patients who are persistently MRSA positive," the study authors conclude. "Ideally this treatment will be conducted in the context of clinical trials, because optimal therapeutic approaches for MRSA, both persistent and new, are not yet known. The study results also reinforce the importance of following current CF infection control guidelines to minimize transmission of MRSA, particularly in outpatient clinics with high CF patient volume."

The Cystic Fibrosis Foundation supported this study. Some of the study authors have disclosed various financial relationships with Nektar; Novartis; PARI; Transave; Aradigm; Bayer; Gilead; Johns Hopkins University; and/or the National Heart, Lung, and Blood Institute.

JAMA. 2010;303:2386-2392.

Clinical Context

CF is the most common lethal autosomal recessive disorder in white individuals. The median survival age is currently older than 37 years. The most common cause of death in CF is secondary pulmonary infection. The most common pathogens responsible for the shortened life span are Pseudomonas aeruginosa and Burkholderia cepacia complex. However, the prevalence of MRSA in the respiratory tract of individuals with CF has increased dramatically, although its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge.

The aim of this study was to determine whether isolation of MRSA from the respiratory tract of patients with CF is associated with worse survival duration vs patients who never have a culture positive for MRSA.

Study Highlights

  • In this cohort study, 19,833 patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States were enrolled.
  • Patients entered the study between January 1996 and December 2006 and were followed up through December 2008.
  • Patients were excluded if they were younger than 6 years (unreliable pulmonary function data) or older than 45 years (milder phenotype not representative of the CF population in general).
  • Cox regression models with time-varying covariates were used to compare survival time between patients with CF with and without respiratory tract MRSA.
  • The main outcome measured was time from age at entry until age at death from any cause.
  • Results demonstrated that in 137,819 patient-years of observation (median, 7.3 years/patient), 2537 patients died, and 5759 patients had MRSA detected.
  • The median estimated survival age was 35.9 years (interquartile range, 25.4 - 52.5 years), and the median age at death was 24.7 years (interquartile range, 19.6 - 32.1 years).
  • At entry into the cohort, those who would go on to have MRSA detected were younger (mean age, 15.1 years; 95% CI, 14.9 - 15.3 vs 16.9 years; 95% CI, 16.8 - 17.1) and were more likely to have low socioeconomic status, pancreatic insufficiency, and cultures positive for P aeruginosa and methicillin-sensitive S aureus (MSSA).
  • Detection of MRSA vs MSSA was associated with worse outcomes in CF; individuals with MRSA were 1.70 times more likely to die than those with MSSA.
  • The mortality rate was 18.3 deaths (95% CI, 17.5 - 19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3 - 30.4) per 1000 patient-years in those with MRSA.
  • Lung transplant recipients with MRSA had worse survival duration vs those without MRSA.
  • Among those with MRSA, the attributable risk percentage for death associated with MRSA was 34.0% (95% CI, 26.7% - 40.4%).
  • The median estimated age of survival was 30.7 years in the MRSA cohort and 36.9 years for the MRSA-negative group (P < .001, log-rank test).
  • The unadjusted HR associated with MRSA was 1.47 (95% CI, 1.32 - 1.62).
  • The adjusted HR in those older than 22 years was 1.37 (95% CI, 1.16 - 1.61).
  • After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk for death (HR, 1.27; 95% CI, 1.11 - 1.45).
  • Limitations of this study include misclassification bias, sampling bias, greater lost to follow-up in the MRSA-negative group vs the MRSA group (9.4% vs 3.2%), and the lack of detailed information from the US Cystic Fibrosis Foundation Patient Registry data on MRSA treatment of individuals in the study cohort.

Clinical Implications

  • The most common cause of death in CF is secondary pulmonary infection from P aeruginosa and B cepacia complex.
  • Detection of MRSA in the respiratory tract of patients with CF was associated with worse survival duration vs those who never have a culture result positive for MRSA.

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