Prospects for the Prevention and Control of Pseudomonal Infection in Children with Cystic Fibrosis

Abstract

Most patients with cystic fibrosis (CF) experience recurrent and chronic endobronchial Pseudomonas aeruginosa infections. It is possible to prevent or delay the onset of these chronic infections in most patients with CF by eliminating cross-infection and by early aggressive antibiotic treatment of the first positive sputum culture and of subsequent intermittent colonisation. Lung tissue damage is caused by activation of the immunologically specific inflammatory defence mechanisms of the lungs, which are initiated by the antibody response and dominated by polymorphonuclear neutrophil leucocytes and their proteolytic and oxidative products. This inflammation induces a phenotypic shift from nonmucoid to mucoid, alginate-producing phenotypes of P. aeruginosa which then grow, endobronchially, as a biofilm. Such biofilms are impossible to eradicate with antibiotics. By using chronic suppressive antibiotic maintenance therapy and anti-inflammatory drugs it is however, possible to maintain the lung function of these patients for a number of years.

Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration

“…All patients were on pancreatic enzyme replacement with 1000 U of lipase/g of fat in the diet, and all routinely underwent preventive antimicrobial therapy consisting of the intravenous administration of two different antibiotics for 15 days every 3 months as recommended by published guidelines. 22 No child received other drugs or clinical interventions that might have affected the intestinal inflammatory state. Children who received probiotics were those whose parents gave their informed consent, and were otherwise unselected.…”

Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa

“…In laboratory-based systems, Pseudomonas aeruginosa forms a biofi lm (several hundred micrometers in thickness) with tower-and mushroom-shaped microcolonies intervened by water channels and void spaces (9) . Pseudomonas aeruginosa, a gram-negative opportunistic human pathogen, is responsible for persistent and often incurable infections in immunocompromised people or patients with cystic fi brosis (10) .…”

Newborn Screening for Cystic Fibrosis: Evaluation of Benefits and Risks and Recommendations for State Newborn Screening Programs—

“…In the Wisconsin study, among subjects followed at the center that used recommended infection-control practices, the median age at first acquisition of P. aeruginosa was age 5 years (29). Infection with mucoid P. aeruginosa leads to irreversible pulmonary damage and death (31). In one cohort study, survival to age 16 years was 53% among children who had chronic P. aeruginosa infections and 84% among those who did not (32).…”

“…Since 1994, new approaches have become available to slow the progression of pulmonary damage or to treat pulmonary bacterial infections in persons with CF (e.g., recombinant human DNase, inhaled tobramycin, and azithromycin) (46)(47)(48)(49). Antibiotics and anti-inflammatory drugs have been reported to slow decline in lung function (31,50). Research is ongoing to determine the appropriate use of such drugs in infants and young children.…”

“…In principle, newborn screening can allow for interventions to delay the onset of chronic P. aeruginosa colonization. A study from Denmark has reported that frequent culturing of specimens from persons with CF and aggressive treatment of first infections with P. aeruginosa avoids or delays the onset of chronic colonization (31). An analysis of UKCFD data has reported lower rates of both transient and chronic P. aeruginosa infection among young children detected by newborn screening (91).…”