Pseudomonas aeruginosa infections in children with cystic fibrosis : Determinants, detection and directed intervention

Pulmonary infections in children with CF are a major cause of morbidity and mortality. In particular, infections with P. aeruginosa lead to rapid pulmonary function decline and are hard to eradicate once established and adapted to the host environment. In this thesis, determinants of host- and bacterial factors for P. aeruginosa infections were investigated. Because of the possible benefit of early detection of P. aeruginosa with respect to eradication strategies, the diagnostic value of direct and indirect detection methods was examined. Also, interventions directed at prevention of initial P. aeruginosa infection by cycled antibiotic prophylaxis and directed at prevention of further pulmonary decline after establishment of P. aeruginosa infection by macrolide antibiotics were analysed. The major findings of this thesis are: -In CF pulmonary infection, the genetic diversity of P. aeruginosa isolates is lower than in P. aeruginosa isolates from infections in non-CF hosts. Clonal genotypes were observed in Dutch patients with CF, but not in patients without CF . -In CF, both eradicated and persistent initial colonising P. aeruginosa isolates show highly variable bacterial characteristics. It is not possible to predict persistence in the airways after initial P. aeruginosa colonisation by estimating these bacterial characteristics alone . -Increasing the culture frequency of oropharyngeal swabs enhances the diagnostic values for P. aeruginosa presence in the lower airways. -Serological measurements of specific anti-P. aeruginosa antibodies are sensitive in detecting chronic P. aeruginosa infections but do not yet contribute substantially in early detection of P. aeruginosa colonisation in the majority of children . -Cycled 3-monthly anti-Pseudomonas antibiotic prophylaxis does not prevent initial and persistent P. aeruginosa infection and subsequent lung function decline in children with CF. -Azithromycin therapy leads to a temporary pulmonary function improvement, but induces rapid macrolide resistance in S. aureus without significant decline in S. aureus isolation. -Transmission of macrolide-resistant S. aureus to household contacts of patients with CF was not proven.