Periodical
Rapid Induction of Multiple Resistance Mechanisms in Aspergillus fumigatusduring Azole Therapy: a Case Study and Review of the Literature
| العنوان: | Rapid Induction of Multiple Resistance Mechanisms in Aspergillus fumigatusduring Azole Therapy: a Case Study and Review of the Literature |
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| المؤلفون: | Camps, Simone M. T., van der Linden, Jan W. M., Li, Yi, Kuijper, Ed J., van Dissel, Jaap T., Verweij, Paul E., Melchers, Willem J. G. |
| المصدر: | Antimicrobial Agents and Chemotherapy; October 2011, Vol. 56 Issue: 1 p10-16, 7p |
| مستخلص: | ABSTRACTNine consecutive isogenic Aspergillus fumigatusisolates cultured from a patient with aspergilloma were investigated for azole resistance. The first cultured isolate showed a wild-type phenotype, but four azole-resistant phenotypes were observed in the subsequent eight isolates. Four mutations were found in the cyp51Agene of these isolates, leading to the substitutions A9T, G54E, P216L, and F219I. Only G54 substitutions were previously proved to be associated with azole resistance. Using a Cyp51A homology model and recombination experiments in which the mutations were introduced into a susceptible isolate, we show that the substitutions at codons P216 and F219 were both associated with resistance to itraconazole and posaconazole. A9T was also present in the wild-type isolate and thus considered a Cyp51A polymorphism. Isolates harboring F219I evolved further into a pan-azole-resistant phenotype, indicating an additional acquisition of a non-Cyp51A-mediated resistance mechanism. Review of the literature showed that in patients who develop azole resistance during therapy, multiple resistance mechanisms commonly emerge. Furthermore, the median time between the last cultured wild-type isolate and the first azole-resistant isolate was 4 months (range, 3 weeks to 23 months), indicating a rapid induction of resistance. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00664804 10986596 |
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| DOI: | 10.1128/AAC.05088-11 |