Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis:: a laboratory-based study with focus on Aspergillus fumigatus azole resistance

Klaus Leth Mortensen; Rasmus Hare Jensen; Helle Krogh Johansen; Marianne Skov; Tacjana Pressler; Susan Julie Howard; Howard Leatherbarrow; Emilia Mellado; Maiken Cavling Arendrup

doi:10.1128/JCM.00213-11

Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance

Klaus Leth Mortensen, Rasmus Hare Jensen, Helle Krogh Johansen, Marianne Skov, Tacjana Pressler, Susan Julie Howard, Howard Leatherbarrow, Emilia Mellado, Maiken Cavling Arendrup

LUKKET: Institut for Immunologi og Mikrobiologi

130 Citationer (Scopus)

Abstract

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 4.5% of the A. fumigatus isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Microbiology
Vol/bind	49
Udgave nummer	6
Sider (fra-til)	2243-51
Antal sider	9
ISSN	0095-1137
DOI	https://doi.org/10.1128/JCM.00213-11
Status	Udgivet - 1 jun. 2011

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10.1128/JCM.00213-11

Citationsformater

Mortensen, K. L., Jensen, R. H., Johansen, H. K., Skov, M., Pressler, T., Howard, S. J., Leatherbarrow, H., Mellado, E., & Arendrup, M. C. (2011). Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance. Journal of Clinical Microbiology, 49(6), 2243-51. https://doi.org/10.1128/JCM.00213-11

Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance. / Mortensen, Klaus Leth; Jensen, Rasmus Hare; Johansen, Helle Krogh et al.

I: Journal of Clinical Microbiology, Bind 49, Nr. 6, 01.06.2011, s. 2243-51.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Mortensen, KL, Jensen, RH, Johansen, HK, Skov, M, Pressler, T, Howard, SJ, Leatherbarrow, H, Mellado, E & Arendrup, MC 2011, 'Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance', Journal of Clinical Microbiology, bind 49, nr. 6, s. 2243-51. https://doi.org/10.1128/JCM.00213-11

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title = "Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis:: a laboratory-based study with focus on Aspergillus fumigatus azole resistance",

abstract = "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 4.5% of the A. fumigatus isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.",

author = "Mortensen, {Klaus Leth} and Jensen, {Rasmus Hare} and Johansen, {Helle Krogh} and Marianne Skov and Tacjana Pressler and Howard, {Susan Julie} and Howard Leatherbarrow and Emilia Mellado and Arendrup, {Maiken Cavling}",

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T2 - a laboratory-based study with focus on Aspergillus fumigatus azole resistance

AU - Mortensen, Klaus Leth

AU - Jensen, Rasmus Hare

AU - Johansen, Helle Krogh

AU - Skov, Marianne

AU - Pressler, Tacjana

AU - Howard, Susan Julie

AU - Leatherbarrow, Howard

AU - Mellado, Emilia

AU - Arendrup, Maiken Cavling

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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 4.5% of the A. fumigatus isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.

AB - 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 4.5% of the A. fumigatus isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.

U2 - 10.1128/JCM.00213-11

DO - 10.1128/JCM.00213-11

M3 - Journal article

C2 - 21508152

SN - 0095-1137

VL - 49

SP - 2243

EP - 2251

JO - Journal of Clinical Microbiology

JF - Journal of Clinical Microbiology

IS - 6

ER -

Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance

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