Early respiratory bacterial detection and anti-staphylococcal antibiotic prophylaxis in young children with cystic fibrosis

Rationale: Consensus is lacking regarding anti-staphylococcal antibiotic prophylaxis use for young children with cystic fibrosis. Prophylaxis is recommended in the UK, but recommended against in the US. Objectives: To test the hypothesis that anti-staphylococcal antibiotic prophylaxis is associated with a decreased risk of Staphylococcus aureus acquisition, but no increased risk of Pseudomonas aeruginosa acquisition. Methods: We undertook a longitudinal observational study of children with cystic fibrosis who were recruited from birth (or their first registry entry in the period) and followed until the age of 4 years (1500 days) using UK CF Trust and US CF Foundation Registries, 2000-2009. Children were excluded if they had a culture positive for S. aureus or P. aeruginosa, or were receiving inhaled antibiotics, at first encounter. Time to first S.aureus and P. aeruginosa detection in the UK/US cohorts were compared using a Cox proportional hazards model. A UK-based analysis compared the same for those receiving flucloxacillin with those who received no prophylaxis. We included the following covariates: sex, age at registry entry, Dornase alfa use, genotype and center size. Results: The primary analysis consisted 1074 UK and 3677 US children. The risk of first detection was greater in US compared to UK for S. aureus (hazard ratio (HR) 5.79; 95% CI: 4.85, 6.90; p