Respiratory bacterial infections in cystic fibrosis

Ciofu, Oana; Hansen, C.R.; Høiby, Niels

doi:10.1097/mcp.0b013e32835f1afc

Cited by 159 publications

(154 citation statements)

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“…Pseudomonas aeruginosa causes chronic respiratory infections in more than 50% of adult CF patients, therefore it is considered the main respiratory pathogen [2]. A period of initial intermittent, recurrent lung colonization is described, when antibiotic treatment can temporarily eradicate the infection.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, increased number of neutrophils, alveolar macrophages and T lymphocytes were found in alveoli of explanted lungs from infected CF patients [4]. Despite the inflammatory response and intensive antibiotic therapy, most infections caused by P. aeruginosa persist for long time, eventually leading to respiratory failure and lung transplantation or death [2]. …”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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Background: Cystic fibrosis (CF) lung infection is a complex condition where opportunistic pathogens and defective immune system cooperate in developing a constant cycle of infection and inflammation. The major pathogen, Pseudomonas aeruginosa, secretes a multitude of virulence factors involved in host immune response and lung tissue damage. In this study, we examined the possible anti-inflammatory effects of molecules inhibiting P. aeruginosa virulence factors.Methods: Pyocyanin, pyoverdine and proteases were measured in bacterial culture supernatant from different P. aeruginosa strains. Inhibition of virulence factors by sub-inhibitory concentrations of clarithromycin and by protease inhibitors was evaluated. Lung inflammatory response was monitored by in vivo bioluminescence imaging in wild-type and CFTR-knockout mice expressing a luciferase gene under the control of a bovine IL-8 promoter.Results: The amount of proteases, pyocyanin and pyoverdine secreted by P. aeruginosa strains was reduced after growth in the presence of a sub-inhibitory dose of clarithromycin. Intratracheal challenge with culture supernatant containing bacteria-released products induced a strong IL-8-mediated response in mouse lungs while lack of virulence factors corresponded to a reduction in bioluminescence emission. Particularly, sole inactivation of proteases by inhibitors Ilomastat and Marimastat also resulted in decreased lung inflammation.Conclusions: Our data support the assumption that virulence factors are involved in P. aeruginosa pro-inflammatory action in CF lungs; particularly, proteases seem to play an important role. Inhibition of virulence factors production and activity resulted in decreased lung inflammation; thus, clarithromycin and protease inhibitors potentially represent additional therapeutic therapies for P. aeruginosa-infected patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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“…26 Readers are referred to several excellent reviews that have highlighted the recent epidemiology of CF pathogens. 26,81,83 …”

Section: Ic3 Other Gram-negative Speciesmentioning

confidence: 99%

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

Saiman

Siegel

LiPuma

et al. 2014

Infect. Control Hosp. Epidemiol.

345

382

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The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.

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“…1,2 However, progressive lung disease associated with chronic respiratory infections and inflammation remains the most common cause of morbidity and mortality in CF. 3 Monitoring changes in the epidemiology of CF pathogens is essential to optimally manage CF lung disease and to understand the potential impact of therapeutic interventions on CF microbiology.…”

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confidence: 99%