Rationale: Staphylococcus aureus and Pseudomonas aeruginosa often infect the airways in cystic fibrosis (CF). Because registry studies show higher prevalence of P. aeruginosa versus S. aureus in older patients with CF, a common assumption is that P. aeruginosa replaces S. aureus over time. In vitro, P. aeruginosa can outgrow and kill S. aureus. However, it is unknown how rapidly P. aeruginosa replaces S. aureus in patients with CF.Methods: We studied a longitudinal cohort of children and adults with CF who had quantitative sputum cultures. We determined the abundance of P. aeruginosa and S. aureus in cfu/ml. We determined the duration and persistence of infections and measured longitudinal changes in culture positivity and abundance for each organism.Measurements and Main Results: Between 2004 and 2017, 134 patients had ≥10 quantitative cultures, with median observation time of 10.15 years. One hundred twenty-four patients had at least one positive culture for P. aeruginosa, and 123 had at least one positive culture for S. aureus. Both species had median abundance of >10⁶ cfu/ml. Culture abundance was stable over time for both organisms. There was an increase in the prevalence of S. aureus/P. aeruginosa coinfection but no decrease in S. aureus prevalence within individuals over time.Conclusions: S. aureus and P. aeruginosa are abundant in CF sputum cultures. Contrary to common assumption, we found no pattern of replacement of S. aureus by P. aeruginosa. Many patients with CF have durable long-term coinfection with these organisms. New strategies are needed to prevent and treat these infections.

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