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Respiratory infection is a major contributor to morbidity and mortality in cystic fibrosis (CF). One infection the CF community is particularly concerned about is methicillin-resistant Staphylococcus aureus (MRSA). Worldwide, the prevalence of MRSA has been rising and the impact on clinical outcomes and optimal prevention and treatment strategies are unclear.Studies have demonstrated MRSA is independently associated with poor clinical outcomes, even after taking into account severity of illness. Additionally, characteristics of MRSA strains, such as small colony variants and borderline oxacillin-resistant S. aureus, may be important in predicting the subsequent clinical course. The treatment of MRSA has had variable results and emergence of resistance to commonly prescribed antibiotics is a concern.The evidence to date supports MRSA infection is independently associated with worse outcomes. The next step is to build upon the current research to expand the knowledge about the impact different strains of MRSA have on infection control strategies and MRSA treatment protocols. Interventions should balance patient safety, efficacy, and treatment burden to improve the quality and length of life in patients with CF.