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

Hurley, Matthew; Fogarty, Andrew W.; McKeever, Tricia M.; Goss, Christopher; Rosenfeld, Margaret; Smyth, Alan R.

Abstract

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<0.001) and P. aeruginosa (HR 1.92; 95% CI: 1.65, 2.24; p<0.001). The UK analysis compared 278 children receiving flucloxacillin and 306 receiving no prophylaxis. Flucloxacillin was not associated with a reduced risk of S. aureus (HR 1.22; 95% CI: 0.74, 2.0; p=0.43), but was associated with an increased risk of P. eruginosa (HR 2.53; 95% CI: 1.71, 3.74; p<0.001) detection. None of the covariates significantly affected the risk estimate in either analysis.

Conclusions: Risk of first detection of S. aureus and P. aeruginosa is greater in US compared to UK. In the UK, the risk of first P. aeruginosa detection is increased among those receiving flucloxacillin compared to those who received no prophylaxis. These observational findings should be explored in a randomized controlled trial.

Citation

Hurley, M., Fogarty, A. W., McKeever, T. M., Goss, C., Rosenfeld, M., & Smyth, A. R. (in press). Early respiratory bacterial detection and anti-staphylococcal antibiotic prophylaxis in young children with cystic fibrosis. Annals of the American Thoracic Society, https://doi.org/10.1513/AnnalsATS.201705-376OC

• Journal Article Type: Article
• Acceptance Date: Oct 11, 2017
• Online Publication Date: Oct 16, 2017
• Deposit Date: Oct 30, 2017
• Publicly Available Date: Oct 17, 2018
• Journal: Annals of the American Thoracic Society
• Print ISSN: 2329-6933
• Electronic ISSN: 2325-6621
• Publisher: American Thoracic Society
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1513/AnnalsATS.201705-376OC
• Keywords: Cystic fibrosis; Children; Antibiotics; Prophylaxis; Infection
• Public URL: https://nottingham-repository.worktribe.com/output/888103
• Publisher URL: https://doi.org/10.1513/AnnalsATS.201705-376OC
• Contract Date: Oct 30, 2017