Dataset Information

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with cystic fibrosis.

ABSTRACT:

Background

There are controversies about the most effective treatment to eradicate first growth of Pseudomonas aeruginosa (P aeruginosa) from the lower airways of patients with cystic fibrosis (CF). UK guidelines recommend oral treatment, but some advocate intravenous (IV) treatment. The objective of this study was to assess the feasibility of conducting a randomised controlled trial comparing two treatment strategies to eradicate P aeruginosa in CF patients.

Methods/principal findings

Two surveys were conducted. Survey [1] included clinicians who were responsible for the treatment of individuals with CF, to assess their clinical practice, opinions and numbers of potentially eligible patients. Survey [2] included adults and young people aged 13 years or more with CF and parents of children with CF aged less than 13 years, identified at six UK CF centres, who fulfilled eligibility criteria for the proposed clinical trial, to assess their views about the interventions and their willingness to participate in the trial. Generally clinicians treat first or new growth of P aeruginosa with oral antibiotics, but 90% reported that they would consider IV treatment of first isolation of P aeruginosa. 74% of clinicians would consider recruiting their patients and 45% of consumers would consider entry for themselves or their children into a trial comparing oral with intravenous antibiotics. The median rate per annum for first or new growths of P aeruginosa in adults was 3% (range 1% to 9%) and in children was 10% (range 3% to 23%). If the trial was conducted across the UK, with a consent rate of 45%, then the number of eligible patients per annum who would be willing to take part in a study would be approximately 41 adults and 203 children.

Conclusions

This work demonstrates the importance of feasibility studies in preparation for multicentre clinical trials. It confirmed the uncertainty amongst clinicians and patients about the clinical question, enabled assessment of the number of potentially eligible patients, the proportion of patients and clinicians prepared to participate and aspects of trial design which might encourage this. It showed that a clinical trial was feasible, but only if patients were recruited from across United Kingdom.

SUBMITTER: Hickey HR

PROVIDER: S-EPMC2832639 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Publications

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with cystic fibrosis.

Hickey Helen R HR Jones Ashley P AP Lenney Warren W Williamson Paula R PR Smyth Rosalind L RL

Trials 20100205

<h4>Background</h4>There are controversies about the most effective treatment to eradicate first growth of Pseudomonas aeruginosa (P aeruginosa) from the lower airways of patients with cystic fibrosis (CF). UK guidelines recommend oral treatment, but some advocate intravenous (IV) treatment. The objective of this study was to assess the feasibility of conducting a randomised controlled trial comparing two treatment strategies to eradicate P aeruginosa in CF patients.<h4>Methods/principal finding ...[more]

PMID: 20137079

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Project description:Pseudomonas aeruginosa is an opportunistic pathogen which is evolving resistance to many currently used antibiotics. While much research has been devoted to the roles of pathogenic P. aeruginosa in cystic fibrosis (CF) patients, less is known of its ecological properties. P. aeruginosa dominates the lungs during chronic infection in CF patients, yet its abundance in some environments is less than that of other diverse groups of pseudomonads. Here, we sought to determine if clinical isolates of P. aeruginosa are vulnerable to environmental pseudomonads that dominate soil and water habitats in one-to-one competitions which may provide a source of inhibitory factors. We isolated a total of 330 pseudomonads from diverse habitats of soil and freshwater ecosystems and competed these strains against one another to determine their capacity for antagonistic activity. Over 900 individual inhibitory events were observed. Extending the analysis to P. aeruginosa isolates revealed that clinical isolates, including ones with increased alginate production, were susceptible to competition by multiple environmental strains. We performed transposon mutagenesis on one isolate and identified an ∼14.8-kb locus involved in antagonistic activity. Only two other environmental isolates were observed to carry the locus, suggesting the presence of additional unique compounds or interactions among other isolates involved in outcompeting P. aeruginosa This collection of strains represents a source of compounds that are active against multiple pathogenic strains. With the evolution of resistance of P. aeruginosa to currently used antibiotics, these environmental strains provide opportunities for novel compound discovery against drug-resistant clinical strains.ImportanceWe demonstrate that clinical CF-derived isolates of P. aeruginosa are susceptible to competition in the presence of environmental pseudomonads. We observed that many diverse environmental strains exhibited varied antagonistic profiles against a panel of clinical P. aeruginosa isolates, suggesting the presence of distinct mechanisms of inhibition among these ecological strains. Understanding the properties of these antagonistic events offers the potential for discoveries of antimicrobial compounds or metabolic pathways important to the development of novel treatments for P. aeruginosa infections.

Project description:BackgroundChronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review.ObjectivesTo assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013).Selection criteriaRandomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis.Data collection and analysisThe authors independently selected trials, assessed them and extracted data.Main resultsSix trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001).Authors' conclusionsVaccines against Pseudomonas aeruginosa cannot be recommended.

Dataset Information

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with cystic fibrosis.

Background

Methods/principal findings

Conclusions

Publications

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with cystic fibrosis.

Similar Datasets

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