Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France

Paugam, A.; Baixench, M.-T.; Demazes-Dufeu, Nadine; Burgel, Pierre‐Régis; Sauter, Elise; Kanaan, R.; Dusser, Daniel; Dupouy‐Camet, Jean; Hubert, D.

doi:10.3109/13693786.2010.503665

Cited by 118 publications

(100 citation statements)

References 28 publications

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“…Moreover, we found that persistently colonized patients were older, and the proportion of females in this group was higher, supporting similar findings reported by others (35). Traditionally, diabetes has been considered a predisposing condition for fungal infections, but surprisingly, a recent French study showed that diabetes was less common in patients with Aspergillus than in those without it (40). We confirm this observation among the persistently colonized patients, and thus, the linkage between Aspergillus and a lower incidence of diabetes should be further explored.…”

Section: Discussionsupporting

confidence: 80%

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Aspergillus Species and Other Molds in Respiratory Samples from Patients with Cystic Fibrosis: a Laboratory-Based Study with Focus on Aspergillus fumigatus Azole Resistance

et al. 2011

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Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among Aspergillus fumigatus isolates. Clinical and demographic data were also analyzed. A total of 3,336 respiratory samples from 287 CF patients were collected during two 6-month periods in 2007 and 2009. Azole resistance was detected using an itraconazole screening agar (4 mg/liter) and the EUCAST method. cyp51A gene sequencing and microsatellite genotyping were performed for isolates from patients harboring azole-resistant A. fumigatus. Aspergillus spp. were present in 145 patients (51%), of whom 63 (22%) were persistently colonized. Twelve patients (4%) harbored other molds. Persistently colonized patients were older, provided more samples, and more often had a chronic bacterial infection. Six of 133 patients (4.5%) harbored azole-nonsusceptible or -resistant A. fumigatus isolates, and five of those six patients had isolates with Cyp51A alterations (M220K, tandem repeat [TR]/L98H, TR/L98H-S297T-F495I, M220I-V101F, and Y431C). All six patients were previously exposed to azoles. Genotyping revealed (i) microevolution for A. fumigatus isolates received consecutively over the 2-year period, (ii) susceptible and resistant isolates (not involving TR/L98H isolates) with identical or very closely related genotypes (two patients), and (iii) two related susceptible isolates and a third unrelated resistant isolate with a unique genotype and the TR/L98H resistance combination (one patient). Aspergilli were frequently found in Danish CF patients, with 4

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Section: Discussionsupporting

confidence: 80%

“…Most studies have focused on A. fumigatus and reported detection rates ranging from 5.9 to 57% (4,7,12,39,40,45). We included both children and adults and showed an A. fumigatus detection rate of more than 33% (both sample periods), which falls in the middle of this wide range.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus Species and Other Molds in Respiratory Samples from Patients with Cystic Fibrosis: a Laboratory-Based Study with Focus on Aspergillus fumigatus Azole Resistance

et al. 2011

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“…Additionally, the similarity between the exopolysaccharides of P. aeruginosa and A. fumigatus, coupled with the interspecies activity of their glycoside hydrolases, suggest the intriguing possibility that exopolysaccharide interactions may occur between organisms during multispecies biofilm formation. Cocolonization with P. aeruginosa and A. fumigatus is not uncommon in patients with chronic pulmonary disease such as cystic fibrosis (38). Although studies of the formation of mixed fungal-bacterial biofilms during pulmonary infection are limited, a recent study of patients with chronic lung disease reported that antibacterial therapy for P. aeruginosa was associated with a reduction in fungal colonization, suggesting the possibility of microbial cooperation (39).…”

Section: Discussionmentioning

confidence: 99%

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity

Snarr

Baker

Bamford

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

100

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Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-D-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3 h from A. fumigatus and PelA h from P. aeruginosa) were found to degrade their respective polysaccharides in vitro. We therefore hypothesized that these glycoside hydrolases could exhibit antibiofilm activity and, further, given the chemical similarity between galactosaminogalactan and Pel, that they might display cross-species activity. Treatment of A. fumigatus with Sph3 h disrupted A. fumigatus biofilms with an EC 50 of 0.4 nM. PelA h treatment also disrupted preformed A. fumigatus biofilms with EC 50 values similar to those obtained for Sph3 h . In contrast, Sph3 h was unable to disrupt P. aeruginosa Pel-based biofilms, despite being able to bind to the exopolysaccharide. Treatment of A. fumigatus hyphae with either Sph3 h or PelA h significantly enhanced the activity of the antifungals posaconazole, amphotericin B, and caspofungin, likely through increasing antifungal penetration of hyphae. Both enzymes were noncytotoxic and protected A549 pulmonary epithelial cells from A. fumigatus-induced cell damage for up to 24 h. Intratracheal administration of Sph3 h was well tolerated and reduced pulmonary fungal burden in a neutropenic mouse model of invasive aspergillosis. These findings suggest that glycoside hydrolases can exhibit activity against diverse microorganisms and may be useful as therapeutic agents by degrading biofilms and attenuating virulence.biofilm | Aspergillus | Pseudomonas | therapeutics | exopolysaccharide

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“…spergillus fumigatus is the most frequently found fungus in the sputum of cystic fibrosis (CF) subjects (18,19). It has been isolated from sputum samples from 56% of patients at our CF center (19).…”

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confidence: 99%

High Prevalence of Azole-Resistant Aspergillus fumigatus in Adults with Cystic Fibrosis Exposed to Itraconazole

Burgel

Baixench

Amsellem

et al. 2012

Antimicrob Agents Chemother

Self Cite

159

116

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Aspergillus fumigatus is the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) or Aspergillus bronchitis in CF subjects. We hypothesized that A. fumigatus isolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection of A. fumigatus. MICs of A. fumigatus isolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method. A. fumigatus was isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. Reduced A. fumigatus susceptibility to itraconazole (MIC, >2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, >0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, >2 mg/liter). Mutations in the cyp51A gene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistant A. fumigatus isolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistant A. fumigatus isolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

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Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France

Cited by 118 publications

References 28 publications

Aspergillus Species and Other Molds in Respiratory Samples from Patients with Cystic Fibrosis: a Laboratory-Based Study with Focus on Aspergillus fumigatus Azole Resistance

Aspergillus Species and Other Molds in Respiratory Samples from Patients with Cystic Fibrosis: a Laboratory-Based Study with Focus on Aspergillus fumigatus Azole Resistance

Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity

High Prevalence of Azole-Resistant Aspergillus fumigatus in Adults with Cystic Fibrosis Exposed to Itraconazole

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