Eradication of early Pseudomonas aeruginosa infection

Department of Clinical Microbiology 9301, Rigshospitalet, University of Copenhagen, Juliane Maries Vej 22, 2100 Copenhagen, Denmark.
Journal of Cystic Fibrosis (Impact Factor: 3.82). 09/2005; 4 Suppl 2(Suppl 2):49-54. DOI: 10.1016/j.jcf.2005.05.018
Source: PubMed

ABSTRACT Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

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Available from: Tania Pressler, Apr 16, 2014
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    • "Initial colonizing strains primarily originate from the environment, each event usually with a unique genotype, displaying wild-type characteristics with a non-mucoid and antibiotic-susceptible phenotype (Burns et al., 2001). 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). "
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    ABSTRACT: The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to establish under which conditions the switch to chronic infection takes place. In association with a recently established sinus surgery treatment program for CF patients at the Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa has been investigated, paralleled by sampling of sputum from the same patients. On the basis of genotyping and phenotypic characterization including transcription profiling, the diversity of the P. aeruginosa populations in the sinuses and the lower airways was investigated and compared. The observations made from several children show that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections.
    The ISME Journal 06/2011; 6(1):31-45. DOI:10.1038/ismej.2011.83 · 9.27 Impact Factor
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    • "Pseudomonas aeruginosa causes opportunistic infections due to its virulence and its capacity to form biofilms (Lyczak et al., 2000). Chronic P. aeruginosa lung infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients (Høiby et al., 2005). This infection is highly resistant to antibiotic treatments and to host immune responses (Høiby et al., 2010). "
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    ABSTRACT: Biofilm-associated chronic Pseudomonas aeruginosa lung infections in patients with cystic fibrosis are virtually impossible to eradicate with antibiotics because biofilm-growing bacteria are highly tolerant to antibiotics and host defense mechanisms. Previously, we found that ginseng treatments protected animal models from developing chronic lung infection by P. aeruginosa. In the present study, the effects of ginseng on the formation of P. aeruginosa biofilms were further investigated in vitro and in vivo. Ginseng aqueous extract at concentrations of 0.5-2.0% did not inhibit the growth of P. aeruginosa, but significantly prevented P. aeruginosa from forming biofilm. Exposure to 0.5% ginseng aqueous extract for 24 h destroyed most 7-day-old mature biofilms formed by both mucoid and nonmucoid P. aeruginosa strains. Ginseng treatment enhanced swimming and twitching motility, but reduced swarming of P. aeruginosa at concentrations as low as 0.25%. Oral administration of ginseng extracts in mice promoted phagocytosis of P. aeruginosa PAO1 by airway phagocytes, but did not affect phagocytosis of a PAO1-filM mutant. Our study suggests that ginseng treatment may help to eradicate the biofilm-associated chronic infections caused by P. aeruginosa.
    FEMS Immunology & Medical Microbiology 02/2011; 62(1):49-56. DOI:10.1111/j.1574-695X.2011.00787.x · 2.55 Impact Factor
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    • "Before antibiotic treatment patients died very young from infections of indigenous pathogens such as Staphylococcus aureus and Haemophilus influenza. The medical success leading to extended life spans of CF patients is coupled to antibiotic treatments with compounds towards which P. aeruginosa is not inherently resistant (Høiby et al., 2005; Hansen et al., 2008). Because antibiotics are used to combat the infections as soon as P. aeruginosa has been diagnosed, it means that persistent colonization and subsequent chronic infection will eventually be associated with development of resistance. "
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    ABSTRACT: Pseudomonas aeruginosa is an opportunistic pathogen ubiquitous to the natural environment but with the capability of moving to the host environment. Long-term infection of the airways of cystic fibrosis patients is associated with extensive genetic adaptation of P. aeruginosa, and we have studied cases of the initial stages of infection in order to characterize the early adaptive processes in the colonizing bacteria. A combination of global gene expression analysis and phenotypic characterization of longitudinal isolates from cystic fibrosis patients revealed well-known characteristics such as conversion to a mucoid phenotype by mucA mutation and increased antibiotic resistance by nfxB mutation. Additionally, upregulation of the atu operon leading to enhanced growth on leucine provides a possible example of metabolic optimization. A detailed investigation of the mucoid phenotype uncovered profound pleiotropic effects on gene expression including reduction of virulence factors and the Rhl quorum sensing system. Accordingly, mucoid isolates displayed a general reduction of virulence in the Caenorhabditis elegans infection model, altogether suggesting that the adaptive success of the mucoid variant extends beyond the benefits of alginate overproduction. In the overall perspective the global phenotype of the adapted variants appears to place them on paths in direction of fully adapted strains residing in long-term chronically infected patients.
    Environmental Microbiology 06/2010; 12(6):1643-58. DOI:10.1111/j.1462-2920.2010.02211.x · 6.24 Impact Factor
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