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

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.

CME Test