| Autor: |
Grossman, Nina T., Pham, Cau D., Cleveland, Angela A., Lockhart, Shawn R. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; November 2014, Vol. 59 Issue: 2 p1030-1037, 8p |
| Abstrakt: |
ABSTRACTCandida parapsilosisis the second or third most common cause of candidemia in many countries. The Infectious Diseases Society of America recommends fluconazole as the primary therapy for C. parapsilosiscandidemia. Although the rate of fluconazole resistance among C. parapsilosisisolates is low in most U.S. institutions, the resistance rate can be as high as 7.5%. This study was designed to assess the mechanisms of fluconazole resistance in 706 incident bloodstream isolates from U.S. hospitals. We sequenced the ERG11and MRR1genes of 122 C. parapsilosisisolates with resistant (30 isolates; 4.2%), susceptible dose-dependent (37 isolates; 5.2%), and susceptible (55 isolates) fluconazole MIC values and used real-time PCR of RNA from 17 isolates to investigate the regulation of MDR1. By comparing these isolates to fully fluconazole-susceptible isolates, we detected at least two mechanisms of fluconazole resistance: an amino acid substitution in the 14-α-demethylase gene ERG11and overexpression of the efflux pump MDR1, possibly due to point mutations in the MRR1transcription factor that regulates MDR1. The ERG11single nucleotide polymorphism (SNP) was found in 57% of the fluconazole-resistant isolates and in no susceptible isolates. The MRR1SNPs were more difficult to characterize, as not all resulted in overexpression of MDR1and not all MDR1overexpression was associated with an SNP in MRR1. Further work to characterize the MRR1SNPs and search for overexpression of other efflux pumps is needed. |
| Databáze: |
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