Faculty Opinions recommendation of Molecular differentiation and antifungal susceptibilities of Candida parapsilosis isolated from patients with bloodstream infections.

2009 ◽  
Author(s):  
Annette Fothergill
Keyword(s):  
Candida Parapsilosis ◽  
Bloodstream Infections ◽  
Molecular Differentiation

scholarly journals Loss of C-5 Sterol Desaturase Activity Results in Increased Resistance to Azole and Echinocandin Antifungals in a Clinical Isolate of Candida parapsilosis

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Jeffrey M. Rybak ◽  
C. Michael Dickens ◽  
Josie E. Parker ◽  
Kelly E. Caudle ◽  
Kayihura Manigaba ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Desaturase Activity ◽  
Candida Parapsilosis ◽  
Prosthetic Valve Endocarditis ◽  
Bloodstream Infections ◽  
Resistant Isolate ◽  
Ergosterol Biosynthesis ◽  
Azole Resistance ◽  
Content Type ◽  
High Level

ABSTRACT Among emerging non-albicans Candida species, Candida parapsilosis is of particular concern as a cause of nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole and echinocandins are considered effective treatments for such infections, recent reports of fluconazole and echinocandin resistance in C. parapsilosis indicate a growing problem. The present study describes a novel mechanism of antifungal resistance in this organism affecting susceptibility to azole and echinocandin antifungals in a clinical isolate obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicated differential expression of several genes in the resistant isolate, including upregulation of ergosterol biosynthesis pathway genes ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, and UPC2. Whole-genome sequencing revealed that the resistant isolate possessed an ERG3 mutation resulting in a G111R amino acid substitution. Sterol profiles indicated a reduction in sterol desaturase activity as a result of this mutation. Replacement of both mutant alleles in the resistant isolate with the susceptible isolate's allele restored wild-type susceptibility to all azoles and echinocandins tested. Disruption of ERG3 in the susceptible and resistant isolates resulted in a loss of sterol desaturase activity, high-level azole resistance, and an echinocandin-intermediate to -resistant phenotype. While disruption of ERG3 in C. albicans resulted in azole resistance, echinocandin MICs, while elevated, remained within the susceptible range. This work demonstrates that the G111R substitution in Erg3 is wholly responsible for the altered azole and echinocandin susceptibilities observed in this C. parapsilosis isolate and is the first report of an ERG3 mutation influencing susceptibility to the echinocandins.

scholarly journals Lodderomyces elongisporus Masquerading as Candida parapsilosis as a Cause of Bloodstream Infections

2007 ◽  
Vol 46 (1) ◽  
pp. 374-376 ◽  
Author(s):  
S. R. Lockhart ◽  
S. A. Messer ◽  
M. A. Pfaller ◽  
D. J. Diekema
Keyword(s):  
Candida Parapsilosis ◽  
Bloodstream Infections

scholarly journals Isolation ofLodderomyces elongisporusfrom the Catheter Tip of a Fungemia Patient in the Middle East

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Suhail Ahmad ◽  
Zia U. Khan ◽  
Molly Johny ◽  
Najat M. Ashour ◽  
Wehad H. Al-Tourah ◽  
...  
Keyword(s):  
Middle East ◽  
Dna Sequencing ◽  
Ribosomal Dna ◽  
Candida Parapsilosis ◽  
Bloodstream Infections ◽  
Suspected Case ◽  
Phenotypic Characteristics ◽  
Catheter Tip

Lodderomyces elongisporusis phenotypically closely related toCandida parapsilosisand has recently been identified as an infrequent cause of bloodstream infections in patients from Asia and Mexico. We report here the isolation ofLodderomyces elongisporusfrom the catheter of a suspected case of fungemia. The identity of the isolate was confirmed by phenotypic characteristics and ribosomal DNA sequencing.

scholarly journals Fluconazole and Voriconazole Resistance in Candida parapsilosis Is Conferred by Gain-of-Function Mutations inMRR1Transcription Factor Gene

2015 ◽  
Vol 59 (10) ◽  
pp. 6629-6633 ◽  
Author(s):  
Joana Branco ◽  
Ana P. Silva ◽  
Raquel M. Silva ◽  
Ana Silva-Dias ◽  
Cidália Pina-Vaz ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Candida Parapsilosis ◽  
Bloodstream Infections ◽  
Azole Resistance ◽  
Transcription Factor Gene ◽  
Gain Of Function ◽  
Content Type ◽  
Factor Gene ◽  
Resistant Strains

ABSTRACTCandida parapsilosisis the second most prevalent fungal agent causing bloodstream infections. Nevertheless, there is little information about the molecular mechanisms underlying azole resistance in this species. Mutations (G1747A, A2619C, and A3191C) in theMRR1transcription factor gene were identified in fluconazole- and voriconazole-resistant strains. Independent expression ofMRR1genes harboring these mutations showed that G1747A (G583R) and A2619C (K873N) are gain-of-function mutations responsible for azole resistance, the first described inC. parapsilosis.

scholarly journals Efficacy of LAMB against Emerging Azole- and Multidrug-Resistant Candida parapsilosis Isolates in the Galleria mellonella Model

2020 ◽  
Vol 6 (4) ◽  
pp. 377
Author(s):  
Ulrike Binder ◽  
Amir Arastehfar ◽  
Lisa Schnegg ◽  
Caroline Hörtnagl ◽  
Suleyha Hilmioğlu-Polat ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Galleria Mellonella ◽  
Drug Efficacy ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Therapeutic Failure ◽  
Reliable Model ◽  
Prompt Action

While being the third leading cause of candidemia worldwide, numerous studies have shown severe clonal outbreaks due to fluconazole-resistant (FLCR) Candida parapsilosis isolates associated with fluconazole therapeutic failure (FTF) with enhanced mortality. More recently, multidrug resistant (MDR) C. parapsilosis blood isolates have also been identified that are resistant to both azole and echinocandin drugs. Amphotericin B (AMB) resistance is rarely reported among C. parapsilosis isolates and proper management of bloodstream infections due to FLZR and MDR isolates requires prompt action at the time of outbreak. Therefore, using a well-established Galleria mellonella model, we assessed whether (a) laboratory-based findings on azole or echinocandin (micafungin) resistance in C. parapsilosis lead to therapeutic failure, (b) LAMB could serve as an efficient salvage treatment option, and (c) distinct mutations in ERG11 impact mortality. Our in vivo data confirm fluconazole inefficacy against FLCR C. parapsilosis isolates carrying Y132F, Y132F + K143R, Y132F + G307A, and G307A + G458S in Erg11p, while LAMB proved to be an efficacious accessible option against both FLCR and MDR C. parapsilosis isolates. Moreover, positive correlation of in vitro and in vivo data further highlights the utility of G. melonella as a reliable model to investigate azole and polyene drug efficacy.

scholarly journals Epidemiology and Antifungal Susceptibility of BloodstreamCandidaIsolates in Quebec: Report on 453 Cases between 2003 and 2005

2008 ◽  
Vol 19 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Guy St-Germain ◽  
Michel Laverdière ◽  
René Pelletier ◽  
Pierre René ◽  
Anne-Marie Bourgault ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Population Based ◽  
Intravascular Catheter ◽  
Fluconazole Resistant ◽  
Candida Lusitaniae

BACKGROUND: Between May 2003 and April 2005, a population-based surveillance ofCandidabloodstream infections was conducted in Quebec. A total of 453 episodes of candidemia (464 yeast isolates) from 54 participating hospitals were studied.RESULTS: The annual incidence rate was three per 100,000 population. Global hospital mortality was 38%. The most common predisposing factors were the presence of an intravascular catheter (80%), use of antibacterial therapy (67%), stay in an intensive care unit (49%), use of parenteral nutrition (32%) and intra-abdominal surgery (31%). Fluconazole alone or in association with other antifungals was used for treatment in over 80% of cases.Candida albicanscomprised 62% of isolates, followed byCandida glabrata(17%),Candida parapsilosis(9%),Candida tropicalis(5%),Candida lusitaniae(3%) andCandida krusei(3%). Of the 288C albicansisolates, seven (2%) were resistant to flucytosine, one to fluconazole and none to itraconazole or voriconazole. Of the 75 non-C albicansspecies isolates with reduced susceptibility to fluconazole (minimum inhibitory concentration [MIC] 16 μg/mL or greater), none were susceptible to itraconazole (MIC 0.12 mg/L or lower), whereas 71 (95%) were susceptible to voriconazole (MIC 1 μg/mL or lower). However, only five of 12 (42%) fluconazole-resistant isolates were susceptible to voriconazole. Posaconazole, ravuconazole and caspofungin displayed a broad spectrum of activity against these isolates, with MICs of 1 mg/L or lower in 56%, 92% and 100% of isolates, respectively. Overall, a correlation (r2>0.87) was observed among increasing fluconazole MICs and the geometric mean MICs of itraconazole, voriconazole, posaconazole and ravuconazole.CONCLUSIONS: These surveillance results when compared with those of the 1993 to 1995 survey confirm little variation in the distribution of species causing invasiveCandidainfection over a 10-year period in Quebec, as well as the continuous excellent overall in vitro activity of fluconazole.

scholarly journals Factors related to outcome of bloodstream infections due to Candida parapsilosis complex

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Francesco Barchiesi ◽  
Elena Orsetti ◽  
Patrizia Osimani ◽  
Carlo Catassi ◽  
Fabio Santelli ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Bloodstream Infections ◽  
Candida Parapsilosis Complex

scholarly journals Molecular differentiation and antifungal susceptibilities of Candida parapsilosis isolated from patients with bloodstream infections

2009 ◽  
Vol 58 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Sun Tee Tay ◽  
Shiang Ling Na ◽  
Jennifer Chong
Keyword(s):  
Candida Parapsilosis ◽  
Susceptibility Testing ◽  
Rapd Analysis ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Candida Metapsilosis ◽  
Significant Difference ◽  
Its Gene ◽  
Candida Orthopsilosis ◽  
Susceptibility Patterns

The genetic heterogeneity and antifungal susceptibility patterns of Candida parapsilosis isolated from blood cultures of patients were investigated in this study. Randomly amplified polymorphic DNA (RAPD) analysis generated 5 unique profiles from 42 isolates. Based on the major DNA fragments of the RAPD profiles, the isolates were identified as RAPD type P1 (29 isolates), P2 (6 isolates), P3 (4 isolates), P4 (2 isolates) and P5 (1 isolate). Sequence analysis of the internal transcribed spacer (ITS) gene of the isolates identified RAPD type P1 as C. parapsilosis, P2 and P3 as Candida orthopsilosis, P4 as Candida metapsilosis, and P5 as Lodderomyces elongisporus. Nucleotide variations in ITS gene sequences of C. orthopsilosis and C. metapsilosis were detected. Antifungal susceptibility testing using Etests showed that all isolates tested in this study were susceptible to amphotericin B, fluconazole, ketoconazole, itraconazole and voriconazole. C. parapsilosis isolates exhibited higher MIC50 values than those of C. orthopsilosis for all of the drugs tested in this study; however, no significant difference in the MICs for these two Candida species was observed. The fact that C. orthopsilosis and C. metapsilosis were responsible for 23.8 and 4.8 % of the cases attributed to C. parapsilosis bloodstream infections, respectively, indicates the clinical relevance of these newly described yeasts. Further investigations of the ecological niche, mode of transmission and virulence of these species are thus essential.

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