Cystic Fibrosis and moulds: updates from the last meeting of the working group

International audienc

Fungal Respiratory Infections in Cystic Fibrosis (CF): Recent Progress and Future Research Agenda

International audienc

Transient colonization of the airways by unusual Aspergillus species in two cystic fibrosis patients

Date du colloque&nbsp;: 06/2009</p

Experimental models of disseminated scedosporiosis with cerebral involvement

Scedosporium apiospermum is a soil fungus which can cause severe and often fatal cerebral infections in both immunocompetent patients in the event of near drowning and immunosuppressed patients such as lung transplant recipients. Because of the low susceptibility of this fungus to antifungal drugs, and the low permeability of the blood-brain barrier (BBB), therapeutic drug monitoring is necessary to reach an effective tissue concentration with limited side effects. Indeed, diffusion of the drug in the brain is dependent on several parameters, such as the integrity of the BBB and the activity of efflux pumps. To evaluate drug diffusion, two experimental models were developed in immunocompetent and immunosuppressed rats. Inocula were administered via the penile vein and a clinical scale (0-9) was established, based on weight and clinical and neurologic signs evaluated by the tail suspension test. Cerebral involvement was confirmed by magnetic resonance imaging and histologic examination of brain sections after hematoxylin-eosin-safran or silver staining. Voriconazole or posaconazole was given to the rats at doses ranging from 10 to 75 mg/kg/day via i.v. or oral routes, respectively. Whatever the immune status, the effective doses (defined by a doubling of the survival time and the absence of neurologic sequelae) were 30 mg/kg/day for voriconazole and 50 mg/kg/day for posaconazole. Overall, the results demonstrated that these models may constitute valuable tools for the performance of pharmacokinetic and pharmacodynamic studies for pharmacokinetic-pharmacodynamic modeling

Towards standardization for mycological examination of sputum samples from Cystic Fibrosis patients: From the French multicenter experience to an international study

Introduction: Prognosis of cystic fibrosis (CF) essentially depends on impairment of the lung function. While considerable attention therefore has been paid over recent decades to the prevention and treatment of bacterial respiratory infections, leading to a marked increase in life expectancy of the patients, prevalence of colonization of the airways by filamentous fungi or yeasts, sometimes leading to true respiratory infections, has been regularly increasing. However, recently, Borman et al. (2010) reported wide variations in the range of the causative fungal pathogens and in their prevalence, related at least to a lack of standardization in the methods used to detect these microorganisms. Here, our aims are: to analyze the impact of the culture conditions used on the detection of specific fungal pathogens throughout the French multicenter experience, and to discuss the methods used in various European or Australian laboratories, in order to carry out an international prospective study that will make possible a standardized protocol for efficient detection of the whole fungal biota that can be encountered in respiratory secretions of CF patients. Results: First, from January 2007 to the end of 2009, a multicenter study was conducted in France encompassing 7 university or general hospitals which agreed to use the same procedure for mycological analysis of sputum saples from CF patients, including prior digestion of the sample with dithiolbutane and inoculation of the digested sample on 6 semi- selective agar-based media ("MucoFong" study – PHRC1902). Data obtained during one year were analyzed using the CHAID (Chi-squared Automatic Interaction Detector) method, which is a statistical approach able to give best association of media to detect a specific pathogen. CHAID is a type of decision tree technique, based upon adjusted significance testing that we apply to our data in order to define the best set of semi-selective media able to isolate 99.99% of the fungal pathogens that were detected in our CF population. Second, the major data of the international survey will be presented, and discussed with the purpose of developing a standardized approach for mycological examination of respiratory secretions from CF patients. Conclusion: Defining the optimal method for mycological analysis of the fungal components of CF lungs microbiome through a large international study is becoming a major requirement. This will make possible not only to analyze the role of some "rare" filamentous species in CF exacerbation or the existence of geographic variations in the fungal species that colonize the airways, but also to study the complexity of the CF lung microbiome as well as its dynamics