Genotypic characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization

Abstract

Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV beta-lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain. Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination.

Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

“…In concordance with previous reports (Burns et al, 2001;Munck et al, 2001;Jelsbak et al, 2007), the majority of the children had acquired unique genotypes suggesting initial lung colonization from environmental sources rather than transmission between patients in our CF Center, the latter being restricted owing to cohort isolation (Høiby and Pedersen, 1989). However, eight specific genotypes were isolated from more than one patient (indicating transmission or common sources of colonization), and 9 of 45 children had more than one genotype isolated from their sputum.…”

“…A total of 31 patients (69%) belonged to group A with successful eradication after aggressive antibiotic treatments, and only three patients (7%) progressed directly to chronic infection (group C). In all, 11 patients (24%) belonged to group B and it is a primary hypothesis here, as suggested by several reports (Munck et al, 2001(Munck et al, , 2003Jelsbak et al, 2007;Mainz et al, 2009) that the bacteria were hiding in the paranasal sinuses. At conclusion of the study, 6 of the 11 group B patients had developed chronic infection after a period of intermittent colonization (Supplementary Table S1).…”

“…Therefore, these results suggest that the direction of migration is mainly downwards at the early stages of infection. If it is assumed that recurrent intermittent lung colonization with the same genotype is associated with persistent sinus colonization, ours and other studies show that around 25% of the CF children may begin with a sinus colonization (Munck et al, 2001;Gibson et al, 2003;Doring et al, 2006), and more than half of all patients will eventually be affected (Mainz et al, 2009). The study further shows that phenotypic and genotypic changes observed in sinus isolates of P. aeruginosa are similar or identical to those often reported for isolates from chronic lung infections in CF patients.…”

“…The early stages of lung disease have therefore been recognized as windows of opportunity to eradicate P. aeruginosa (Burns et al, 2001), and clinical trials have shown that early aggressive treatment is beneficial for the patient and delays transition into a chronic infection (Høiby et al, 2005;Taccetti et al, 2005). Following eradication, a new acquisition is often with a different genotype, but some studies have shown that in approximately 25% of the cases re-colonization occurs with the same genotype of P. aeruginosa (Munck et al, 2001;Gibson et al, 2003;Doring et al, 2006). Re-colonization could be either from a persistent environmental source or from an undetected reservoir in the patient upper airways such as the paranasal sinuses (Jelsbak et al, 2007).…”

Inhaled Antibiotics for Lower Airway Infections

“…These large, well-designed studies have demonstrated that P. aeruginosa can be eradicated in both the lower and upper airways in the majority of patients, and patients remain P. aeruginosa free for months (21), even with inhaled tobramycin monotherapy (18). The impact on clinical endpoints, such as frequency of exacerbations, is less clear (18), and these patients were too young to reproducibly perform pulmonary function testing.…”