Short communicationSusceptibility to five antifungals of Aspergillus fumigatus strains isolated from chronically colonised cystic fibrosis patients receiving azole therapy
Introduction
Cystic fibrosis (CF) patients are continuously exposed to microorganisms that may colonise their lungs, reducing respiratory function and enhancing pulmonary problems. Allergic bronchopulmonary aspergillosis (ABPA) is an intense allergic reaction, mainly in response to the presence of Aspergillus fumigatus, which can affect up to 15% of CF patients [1]. This allergic disease is normally treated with prescription of oral corticosteroid therapy and in a few critical clinical cases azole antifungals may be used [1], [2].
Aspergillus fumigatus is one of the most frequently isolated fungi from the lungs of CF patients [1]. It is commonly susceptible to the commercially available antifungals such as amphotericin B, caspofungin, itraconazole, voriconazole and posaconazole [3]. It was recently shown that CF patients may be chronically colonised with the same A. fumigatus strain over several years [4], [5]. Exposure of A. fumigatus strains to distinct conditions and stressful therapies over long periods may sporadically lead to alterations in their susceptibility and to treatment failure [6], [7]. The objective of the present work was to evaluate the susceptibility to azole and non-azole antifungals of 159 isolates of A. fumigatus collected from 11 patients, some of whom had been treated with azole antifungal therapy.
Section snippets
Patients
A group of 11 patients admitted to Hospital S. João (Porto, Portugal) and diagnosed with CF were studied. The diagnosis of CF was confirmed by screening mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein and positive evaluation of the sweat test. Patient age ranged from 15 years to 51 years. Patients were selected for this study following confirmation of chronic colonisation with A. fumigatus (more than three sputum samples with A. fumigatus in
Results
Amongst the entire A. fumigatus collection, no resistant isolates (MIC/MEC ≥ 4 μg/mL) were identified to the antifungals amphotericin B, caspofungin, itraconazole and voriconazole (Table 1). The susceptibility of a few isolates was classified as intermediate to amphotericin B (3 isolates) and itraconazole (18 isolates), and a single A. fumigatus isolate was identified outside of the epidemiological cut-off of 0.25 μg/mL for posaconazole (this last isolate showed a susceptibility of 0.5 μg/mL for
Discussion
Oral corticosteroid therapy remains the first therapy for ABPA and there is still no consensus regarding how, how long or when antifungal drugs should be employed for treatment of patients with ABPA or those colonised with Aspergillus spp. [2], [14]. Patients included in this study received azole antifungal therapy due to serious haemoptysis and/or decrease of respiratory function and clinical deterioration following administration of antibacterial treatment and/or corticosteroid therapy. In
Acknowledgments
The authors are grateful to Maria Luz Dias and Isabel Santos for excellent technical assistance.
Funding: This work was supported by grants from Fundação Calouste Gulbenkian (no. 35-9924-S/2009), University of Porto and Santander Totta. RA was co-financed by the European Social Fund. IPATIMUP is partially supported by Fundação para a Ciência e Tecnologia (FCT), Programa Operacional Ciência e Inovação (POCI) and Programa Operacional do Potencial Humano (POPH – QREN).
Competing interests: None
References (15)
- et al.
Cystic fibrosis
Lancet
(2009) - et al.
Susceptibility of environmental versus clinical strains of pathogenic Aspergillus
Int J Antimicrob Agents
(2007) - et al.
Molecular typing and colonization patterns of Aspergillus fumigatus in patients with cystic fibrosis
J Cyst Fibros
(2009) - et al.
Simple and highly discriminatory microsatellite-based multiplex PCR for Aspergillus fumigatus strain typing
Clin Microbiol Infect
(2009) To treat or not to treat with antifungal agents?
J Cyst Fibros
(2005)- et al.
Allergic bronchopulmonary aspergillosis in cystic fibrosis-state of the art: Cystic Fibrosis Foundation Consensus Conference
Clin Infect Dis
(2003) - et al.
High-resolution genotyping of Aspergillus fumigatus isolates recovered from chronically colonised patients with cystic fibrosis
Eur J Clin Microbiol Infect Dis
(2008)
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