Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 24, Number 9—September 2018
Research Letter

Fluconazole-Resistant Candida parapsilosis Bloodstream Isolates with Y132F Mutation in ERG11 Gene, South Korea

Yong Jun Choi1, Yae-Jean Kim1, Dongeun Yong, Jung-Hyun Byun, Taek Soo Kim, Yun Sil Chang, Min Ji Choi, Seung Ah Byeon, Eun Jeong Won, Soo Hyun Kim, Myung Geun Shin, and Jong Hee ShinComments to Author 
Author affiliations: Chonnam National University Medical School, Gwangju, South Korea (Y.J. Choi, M.J. Choi, S.A. Byeon, E.J. Won, S.H. Kim, M.G. Shin, J.H. Shin); Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (Y.-J. Kim, Y.S. Chang); Yonsei University College of Medicine, Seoul (D. Yong, J.-H. Byun); Seoul National University Hospital, Seoul (T.S. Kim)

Main Article

Table

Molecular characterization of 47 fluconazole-resistant isolates and 20 fluconazole-susceptible isolates of Candida parapsilosis, South Korea*

Microsatellite
genotypes†
Hospital
No. isolates
MICs, mg/L‡
Amino acid substitutions§ Isolation year (no. patients)
FLC
VRC
Erg11p
Mrr1p
Tac1p
Upc2p
Fluconazole-resistant with Y132F in Erg11p, n = 30 isolates
M1 A 8 8–32 0.25–0.5 Y132F K177N 2006 (1), 2009 (1), 2010 (2), 2011 (2), 2012 (1), 2013 (1)
B 3 16–32 0.5 Y132F K177N 2012 (2), 2013 (1)
M2 A 10 8–32 0.125–0.5 Y132F K177N 2012 (1), 2016 (9)
M3 A 3 8–16 0.25 Y132F K177N, Q1053* 2007 (1), 2011 (1), 2012 (1)
M4 A 2 8–>64 0.5–4 Y132F K177N 2013 (1), 2016 (1)
M5 A 1 32 0.25 Y132F K177N 2012 (1)
M6 A 1 8 0.5 Y132F K177N 2013 (1)
M7 A 1 8 0.25 Y132F K177N 2016 (1)
M8
C
1
64
2

Y132F



2016 (1)
Other fluconazole-resistant, n = 17 isolates
M9 D 2 >64 1 G583R 2007 (1), 2009 (1)
M10 E 1 16 0.5 R398I L877P 2005 (1)
M11 A 1 8 0.25 2006 (1)
M12 E 1 8 0.25 R398I L877P 2011 (1)
M13 F 1 16 0.06 R398I L877P 2011 (1)
M14 E 1 8 0.125 R398I L877P 2012 (1)
M15 G 1 8 0.125 R398I L877P 2012 (1)
M16 G 1 8 0.06 R398I L877P 2012 (1)
M17 E 1 8 0.125 N900D 2012 (1)
M18 C 1 8 0.125 R398I P250S L877P 2012 (1)
M19 C 1 8 0.25 R398I S1081P L877P 2012 (1)
M20 D 1 8 0.125 R398I D394N 2012 (1)
M21 E 1 32 0.5 R398I P295R L877P 2015 (1)
M22 E 1 16 0.125 R398I 2015 (1)
M23 H 1 32 0.125 K128N W872C 2015 (1)
M24
E
1
16
0.25


G927D


2016 (1)
Fluconazole-susceptible controls
M3 A 1 1 0.03 K177N, Q1053* 2010 (1)
M25 C 2 0.5 0.03 R398I 2012 (2)
M26 F 2 0.5 0.03–0.06 R208G 2012 (1), 2013 (1)
M27 A 1 2 0.06 2010 (1)
M28 A 1 0.5 0.03 K177N, Q1053* 2011 (1)
M29 A 1 1 0.06 L877P 2011 (1)
M30 A 1 1 0.03 R208G 2012 (1)
M31 A 1 0.5 0.03 R208G 2012 (1)
M32 E 1 2 0.03 2012 (1)
M33 G 1 0.5 0.03 R208G 2012 (1)
M34 G 1 0.5 0.03 2012 (1)
M35 A 1 0.5 0.03 R208G 2013 (1)
M36 A 1 1 0.06 R398I D394N 2013 (1)
M37 A 1 0.5 0.03 R398I 2013 (1)
M38 D 1 0.5 0.06 R398I 2014 (1)
M39 D 1 0.5 0.06 R208G 2014 (1)
M40 E 1 0.5 0.03 R208G 2015 (1)
M41 A 1 1 0.03 R398I L877P 2015 (1)

*CLSI, Clinical and Laboratory Standards Institute; FLC, fluconazole; VRC, voriconazole.
†For microsatellite typing, each strain was characterized by a genotype resulting from combination of the sizes of the 4 markers (CP1, CP4, CP6, and B). See the Technical Appendix Figure for results of microsatellite genotyping presented as an UPGMA tree.
‡Antifungal MICs were determined by the CLSI M27–A3 broth microdilution method (7). The fluconazole MICs of 30 Y132F isolates determined by Etest were ≥8 mg/L. All 67 isolates tested were susceptible to amphotericin B (MIC 0.25–1 mg/L) and micafungin (MIC 0.25–2 mg/L) according to the CLSI method.
§All were homozygote alleles except for 6 heterozygote alleles (Q1053,* G583R, P250S, P295R, W872C, and G927D) in Mrr1p.

Main Article

References
  1. Pfaller  MA, Jones  RN, Doern  GV, Sader  HS, Messer  SA, Houston  A, et al.; The SENTRY Participant Group. Bloodstream infections due to Candida species: SENTRY antimicrobial surveillance program in North America and Latin America, 1997-1998. Antimicrob Agents Chemother. 2000;44:74751. DOIPubMedGoogle Scholar
  2. Sandven  P. Epidemiology of candidemia. Rev Iberoam Micol. 2000;17:7381.PubMedGoogle Scholar
  3. Souza  AC, Fuchs  BB, Pinhati  HM, Siqueira  RA, Hagen  F, Meis  JF, et al. Candida parapsilosis resistance to fluconazole: molecular mechanisms and in vivo impact in infected Galleria mellonella larvae. Antimicrob Agents Chemother. 2015;59:65817. DOIPubMedGoogle Scholar
  4. Grossman  NT, Pham  CD, Cleveland  AA, Lockhart  SR. Molecular mechanisms of fluconazole resistance in Candida parapsilosis isolates from a U.S. surveillance system. Antimicrob Agents Chemother. 2015;59:10307. DOIPubMedGoogle Scholar
  5. Berkow  EL, Manigaba  K, Parker  JE, Barker  KS, Kelly  SL, Rogers  PD. Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis. Antimicrob Agents Chemother. 2015;59:594250. DOIPubMedGoogle Scholar
  6. Asadzadeh  M, Ahmad  S, Al-Sweih  N, Khan  Z. Epidemiology and molecular basis of resistance to fluconazole among clinical Candida parapsilosis isolates in Kuwait. Microb Drug Resist. 2017;23:96672. DOIPubMedGoogle Scholar
  7. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts—third edition: approved standard (M27–A3). Wayne (PA): The Institute; 2008.
  8. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts: fourth informational supplement (M27–S4). Wayne (PA): The Institute; 2012.
  9. Lockhart  SR, Etienne  KA, Vallabhaneni  S, Farooqi  J, Chowdhary  A, Govender  NP, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64:13440. DOIPubMedGoogle Scholar
  10. Welsh  RM, Bentz  ML, Shams  A, Houston  H, Lyons  A, Rose  LJ, et al. Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic health care surface. J Clin Microbiol. 2017;55:29963005. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

Page created: August 17, 2018
Page updated: August 17, 2018
Page reviewed: August 17, 2018
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external