TY - JOUR
T1 - Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of Candida tropicalis blood isolates
AU - Arastehfar, Amir
AU - Daneshnia, Farnaz
AU - Hafez, Ahmed
AU - Khodavaisy, Sadegh
AU - Najafzadeh, Mohammad Javad
AU - Charsizadeh, Arezoo
AU - Zarrinfar, Hossein
AU - Salehi, Mohammadreza
AU - Shahrabadi, Zahra Zare
AU - Sasani, Elahe
AU - Zomorodian, Kamiar
AU - Pan, Weihua
AU - Hagen, Ferry
AU - Ilkit, Macit
AU - Kostrzewa, Markus
AU - Boekhout, Teun
N1 - Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Candida tropicalis is one of the major candidaemia agents, associated with the highest mortality rates among Candida species, and developing resistance to azoles. Little is known about the molecular mechanisms of azole resistance, genotypic diversity, and the clinical background of C. tropicalis infections. Consequently, this study was designed to address those questions. Sixty-four C. tropicalis bloodstream isolates from 62 patients from three cities in Iran (2014–2019) were analyzed. Strain identification, antifungal susceptibility testing, and genotypic diversity analysis were performed by MALDI-TOF MS, CLSI-M27 A3/S4 protocol, and amplified fragment length polymorphism (AFLP) fingerprinting, respectively. Genes related to drug resistance (ERG11, MRR1, TAC1, UPC2, and FKS1 hotspot9s) were sequenced. The overall mortality rate was 59.6% (37/62). Strains were resistant to micafungin [minimum inhibitory concentration (MIC) ≥1 μg/ml, 2/64], itraconazole (MIC > 0.5 μg/ml, 2/64), fluconazole (FLZ; MIC ≥ 8 μg/ml, 4/64), and voriconazole (MIC ≥ 1 μg/ml, 7/64). Pan-azole and FLZ + VRZ resistance were observed in one and two isolates, respectively, while none of the patients were exposed to azoles. MRR1 (T255P, 647S), TAC1 (N164I, R47Q), and UPC2 (T241A, Q340H, T381S) mutations were exclusively identified in FLZ-resistant isolates. AFLP fingerprinting revealed five major and seven minor genotypes; genotype G4 was predominant in all centers. The increasing number of FLZ-R C. tropicalis blood isolates and acquiring FLZ-R in FLZ-naive patients limit the efficiency of FLZ, especially in developing countries. The high mortality rate warrants reaching a consensus regarding the nosocomial mode of C. tropicalis transmission.
AB - Candida tropicalis is one of the major candidaemia agents, associated with the highest mortality rates among Candida species, and developing resistance to azoles. Little is known about the molecular mechanisms of azole resistance, genotypic diversity, and the clinical background of C. tropicalis infections. Consequently, this study was designed to address those questions. Sixty-four C. tropicalis bloodstream isolates from 62 patients from three cities in Iran (2014–2019) were analyzed. Strain identification, antifungal susceptibility testing, and genotypic diversity analysis were performed by MALDI-TOF MS, CLSI-M27 A3/S4 protocol, and amplified fragment length polymorphism (AFLP) fingerprinting, respectively. Genes related to drug resistance (ERG11, MRR1, TAC1, UPC2, and FKS1 hotspot9s) were sequenced. The overall mortality rate was 59.6% (37/62). Strains were resistant to micafungin [minimum inhibitory concentration (MIC) ≥1 μg/ml, 2/64], itraconazole (MIC > 0.5 μg/ml, 2/64), fluconazole (FLZ; MIC ≥ 8 μg/ml, 4/64), and voriconazole (MIC ≥ 1 μg/ml, 7/64). Pan-azole and FLZ + VRZ resistance were observed in one and two isolates, respectively, while none of the patients were exposed to azoles. MRR1 (T255P, 647S), TAC1 (N164I, R47Q), and UPC2 (T241A, Q340H, T381S) mutations were exclusively identified in FLZ-resistant isolates. AFLP fingerprinting revealed five major and seven minor genotypes; genotype G4 was predominant in all centers. The increasing number of FLZ-R C. tropicalis blood isolates and acquiring FLZ-R in FLZ-naive patients limit the efficiency of FLZ, especially in developing countries. The high mortality rate warrants reaching a consensus regarding the nosocomial mode of C. tropicalis transmission.
KW - Azole resistance
KW - Candida tropicalis
KW - Candidaemia
KW - ERG11; MRR1; TAC1; UPC2
KW - FKS1
KW - Genotyping
UR - https://www.scopus.com/pages/publications/85089128801
U2 - 10.1093/mmy/myz124
DO - 10.1093/mmy/myz124
M3 - Article
C2 - 31828316
AN - SCOPUS:85089128801
SN - 1369-3786
VL - 58
SP - 766
EP - 773
JO - Medical mycology
JF - Medical mycology
IS - 6
ER -