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Published on: January 22, 2021
Early Respiratory Bacterial Detection and Antistaphylococcal Antibiotic Prophylaxis in Young Children with Cystic
Matthew N Hurley1,2, Andrew Fogarty3, Tricia M McKeever3
11 Division of Child Health, Obstetrics & Gynaecology, University of Nottingham, and.
Insights
Antistaphylococcal antibiotic prophylaxis in children with cystic fibrosis did not reduce Staphylococcus aureus acquisition. Flucloxacillin increased Pseudomonas aeruginosa risk in the UK, warranting further trials.
Area of Science:
- Pediatric Pulmonology
- Infectious Diseases
- Pharmacology
Background:
- Consensus is lacking on antistaphylococcal antibiotic prophylaxis for young children with cystic fibrosis (CF).
- Prophylaxis is recommended in the UK but not the US for CF patients.
- Staphylococcus aureus and Pseudomonas aeruginosa are key pathogens in CF lung disease.
Purpose of the Study:
- To evaluate the association between antistaphylococcal antibiotic prophylaxis and the risk of S. aureus and P. aeruginosa acquisition in children with CF.
- To compare S. aureus and P. aeruginosa acquisition rates between UK and US cohorts.
- To assess the impact of flucloxacillin prophylaxis on S. aureus and P. aeruginosa detection in the UK.
Main Methods:
- Longitudinal observational study using UK and US CF registry data (2000-2009).
- Followed children from birth to age 4, excluding those with prior S. aureus/P. aeruginosa or inhaled antibiotic use.
- Compared time to first detection of S. aureus and P. aeruginosa using Cox proportional hazards models.
Main Results:
- US children had a significantly higher risk of S. aureus (HR 5.79) and P. aeruginosa (HR 1.92) detection compared to UK children.
- In the UK, flucloxacillin prophylaxis was not associated with reduced S. aureus detection (HR 1.22).
- Flucloxacillin use in the UK was associated with an increased risk of P. aeruginosa detection (HR 2.53).
Conclusions:
- The risk of S. aureus and P. aeruginosa acquisition is higher in US children with CF than in UK children.
- Antistaphylococcal antibiotic prophylaxis with flucloxacillin in the UK did not reduce S. aureus acquisition and increased P. aeruginosa acquisition risk.
- Further investigation via randomized controlled trials is recommended to examine these observational findings.
Rationale:
Consensus is lacking regarding antistaphylococcal antibiotic prophylaxis use for young children with cystic fibrosis. Prophylaxis is recommended in the United Kingdom, but it is recommended against in the United States.
Objectives:
To test the hypothesis that antistaphylococcal 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 from their first registry entry in the period) and followed until the age of 4 years (1,500 d) using 2000-2009 data from the UK Cystic Fibrosis Trust and Cystic Fibrosis Foundation registries. Children were excluded if they had a positive culture result for S. aureus or P. aeruginosa, or if they were receiving inhaled antibiotics, at the first encounter. Time to first S. aureus and P. aeruginosa detection in the UK/U.S. cohorts was 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 comprised 1,074 UK and 3,677 U.S. children. The risk of first detection was greater in U.S. children than in UK children for S. aureus (hazard ratio [HR], 5.79; 95% confidence interval [CI], 4.85, 6.90; P < 0.001) and P. aeruginosa (HR, 1.92; 95% CI, 1.65, 2.24; P < 0.001). In the UK analysis, we compared 278 children receiving flucloxacillin and 306 receiving no prophylaxis. Flucloxacillin was not associated with a reduced risk of S. aureus detection (HR, 1.22; 95% CI, 0.74, 2.0; P = 0.43), but it was associated with an increased risk of P. aeruginosa detection (HR, 2.53; 95% CI, 1.71, 3.74; P < 0.001). None of the covariates significantly affected the risk estimate in either analysis.
Conclusions:
The risk of first detection of S. aureus and P. aeruginosa was greater in the United States than in the United Kingdom. In the United Kingdom, the risk of first P. aeruginosa detection was increased among those receiving flucloxacillin compared with those who received no prophylaxis. These observational findings should be examined in randomized controlled trials.
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