cyp51A-Based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany
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cyp51A-Based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany. / Bader, Oliver; Weig, Michael; Reichard, Utz; Lugert, Raimond; Kuhns, Martin; Christner, Martin; Held, Jürgen; Peter, Silke; Schumacher, Ulrike; Buchheidt, Dieter; Tintelnot, Kathrin; Groß, Uwe; MykoLabNet-D Partners.
in: ANTIMICROB AGENTS CH, Jahrgang 57, Nr. 8, 01.08.2013, S. 3513-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - cyp51A-Based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany
AU - Bader, Oliver
AU - Weig, Michael
AU - Reichard, Utz
AU - Lugert, Raimond
AU - Kuhns, Martin
AU - Christner, Martin
AU - Held, Jürgen
AU - Peter, Silke
AU - Schumacher, Ulrike
AU - Buchheidt, Dieter
AU - Tintelnot, Kathrin
AU - Groß, Uwe
AU - MykoLabNet-D Partners
PY - 2013/8/1
Y1 - 2013/8/1
N2 - Since the mid-1990s, a steady increase in the occurrence of itraconazole-resistant Aspergillus fumigatus isolates has been observed in clinical contexts, leading to therapeutic failure in the treatment of aspergillosis. This increase has been predominantly linked to a single allele of the cyp51A gene, termed TR/L98H, which is thought to have arisen through the use of agricultural azoles. Here, we investigated the current epidemiology of triazole-resistant A. fumigatus and underlying cyp51A mutations in clinical samples in Germany. From a total of 527 samples, 17 (3.2%) showed elevated MIC0 values (the lowest concentrations with no visible growth) for at least one of the three substances (itraconazole, voriconazole, and posaconazole) tested. The highest prevalence of resistant isolates was observed in cystic fibrosis patients (5.2%). Among resistant isolates, the TR/L98H mutation in cyp51A was the most prevalent, but isolates with the G54W and M220I substitutions and the novel F219C substitution were also found. The isolate with the G54W substitution was highly resistant to both itraconazole and posaconazole, while all others showed high-level resistance only to itraconazole. For the remaining six isolates, no mutations in cyp51A were found, indicating the presence of other mechanisms. With the exception of the strains carrying the F219C and M220I substitutions, many itraconazole-resistant strains also showed cross-resistance to voriconazole and posaconazole with moderately increased MIC0 values. In conclusion, the prevalence of azole-resistant A. fumigatus in our clinical test set is lower than that previously reported for other countries. Although the TR/L98H mutation frequently occurs among triazole-resistant strains in Germany, it is not the only resistance mechanism present.
AB - Since the mid-1990s, a steady increase in the occurrence of itraconazole-resistant Aspergillus fumigatus isolates has been observed in clinical contexts, leading to therapeutic failure in the treatment of aspergillosis. This increase has been predominantly linked to a single allele of the cyp51A gene, termed TR/L98H, which is thought to have arisen through the use of agricultural azoles. Here, we investigated the current epidemiology of triazole-resistant A. fumigatus and underlying cyp51A mutations in clinical samples in Germany. From a total of 527 samples, 17 (3.2%) showed elevated MIC0 values (the lowest concentrations with no visible growth) for at least one of the three substances (itraconazole, voriconazole, and posaconazole) tested. The highest prevalence of resistant isolates was observed in cystic fibrosis patients (5.2%). Among resistant isolates, the TR/L98H mutation in cyp51A was the most prevalent, but isolates with the G54W and M220I substitutions and the novel F219C substitution were also found. The isolate with the G54W substitution was highly resistant to both itraconazole and posaconazole, while all others showed high-level resistance only to itraconazole. For the remaining six isolates, no mutations in cyp51A were found, indicating the presence of other mechanisms. With the exception of the strains carrying the F219C and M220I substitutions, many itraconazole-resistant strains also showed cross-resistance to voriconazole and posaconazole with moderately increased MIC0 values. In conclusion, the prevalence of azole-resistant A. fumigatus in our clinical test set is lower than that previously reported for other countries. Although the TR/L98H mutation frequently occurs among triazole-resistant strains in Germany, it is not the only resistance mechanism present.
KW - Alleles
KW - Antifungal Agents
KW - Aspergillosis
KW - Aspergillus fumigatus
KW - Cytochrome P-450 Enzyme System
KW - Drug Resistance, Fungal
KW - Fungal Proteins
KW - Germany
KW - Humans
KW - Itraconazole
KW - Microbial Sensitivity Tests
KW - Mutation
KW - Prevalence
KW - Pyrimidines
KW - Triazoles
U2 - 10.1128/AAC.00167-13
DO - 10.1128/AAC.00167-13
M3 - SCORING: Journal article
C2 - 23669382
VL - 57
SP - 3513
EP - 3517
JO - ANTIMICROB AGENTS CH
JF - ANTIMICROB AGENTS CH
SN - 0066-4804
IS - 8
ER -
