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

Background: We aimed to evaluate the correlation of caspofungin E-tests with the prognosis and response to caspofungin therapy of Candida parapsilosis complex bloodstream infections in children hospitalized in pediatric intensive care unit.Methods: All children who had C.parapsilosis complex bloodstream infections and who were treated with caspofungin were included in this retrospective study. For each patient, the following parameters, including all consecutive blood and central venous catheter (CVC) cultures, duration between diagnosis and CVC removal, mortality rate, relapses of the C.parapsilosis complex infections as well as the demographic features, were recorded.Results: The study covered 53 patients with a median age of 11 months. The median duration of C.parapsilosis complex isolation was 31 days. The CVC rescue rate was 33.3% under caspofungin treatment. In 92.4% of the patients, the negative culture was achieved within a median duration of 14 days. The rate of relapses was 18.9%. The overall mortality rate was %37.7 (20 patients) and 30-days mortality rate was 7.5% (4 patients).Conclusions: Caspofungin is an attractive option due to its effects on biofilms in vivo, while the reflection of its affect on C.parapsilosis complex was limited in our study, but it should not be underestimated in children who strongly need the presence of central venous catheters. Moreover, in vivo susceptibility might not always guarantee good clinical response in clinical practice. The clinicians should weigh their priority for their patients and choose the optimal antifungal therapy for C.parapsilosis complex infections in children.

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

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1147055.604171 ◽

2009 ◽

Author(s):

Annette Fothergill

Keyword(s):

Candida Parapsilosis ◽

Bloodstream Infections ◽

Molecular Differentiation

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Exposure of Candida parapsilosis complex to agricultural azoles: An overview of the role of environmental determinants for the development of resistance

The Science of The Total Environment ◽

10.1016/j.scitotenv.2018.09.096 ◽

2019 ◽

Vol 650 ◽

pp. 1231-1238 ◽

Cited By ~ 9

Author(s):

Raimunda Sâmia Nogueira Brilhante ◽

Lucas Pereira de Alencar ◽

Silviane Praciano Bandeira ◽

Jamille Alencar Sales ◽

Antônio José de Jesus Evangelista ◽

...

Keyword(s):

Candida Parapsilosis ◽

Environmental Determinants ◽

Development Of Resistance ◽

Candida Parapsilosis Complex

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00651-17 ◽

2017 ◽

Vol 61 (9) ◽

Cited By ~ 14

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.

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

Journal of Clinical Microbiology ◽

10.1128/jcm.01790-07 ◽

2007 ◽

Vol 46 (1) ◽

pp. 374-376 ◽

Cited By ~ 61

Author(s):

S. R. Lockhart ◽

S. A. Messer ◽

M. A. Pfaller ◽

D. J. Diekema

Keyword(s):

Candida Parapsilosis ◽

Bloodstream Infections

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Rapid Detection of Echinocandins Resistance by MALDI-TOF MS in Candida parapsilosis Complex

Microorganisms ◽

10.3390/microorganisms8010109 ◽

2020 ◽

Vol 8 (1) ◽

pp. 109

Author(s):

Ana Emília M. Roberto ◽

Danilo E. Xavier ◽

Esteban E. Vidal ◽

Cláudia Fernanda de L. Vidal ◽

Rejane P. Neves ◽

...

Keyword(s):

Mass Spectrometry ◽

Incubation Time ◽

Candida Parapsilosis ◽

Clinical Laboratory ◽

Antifungal Susceptibility ◽

Reference Method ◽

Sensu Stricto ◽

Maldi Tof ◽

Separation Parameter ◽

Candida Parapsilosis Complex

Mass spectrometry by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) was used to identify and differentiate the pattern of susceptibility of clinical isolates of Candida parapsilosis complex. 17 C. parapsilosis sensu stricto, 2 C. orthopsilosis, and 1 C. metapsilosis strains were obtained from blood cultures, and three different inocula (103, 105, and 107 CFU/mL) were evaluated against three echinocandins at concentrations ranging from 0.03 to 16 µg/mL after incubation of 1 h, 2 h, and 3 h. Drug-free control was used. The spectra obtained at these concentrations were applied to generate composite correlation index (CCI) matrices for each yeast individually. After cross correlations and autocorrelations of each spectra with null (zero) and maximal (16) concentrations, the CCI was used as separation parameter among spectra. Incubation time and inoculum were critical factors to reach higher precision and reliability of this trial. With an incubation time of 3 h and inoculum of 107 CFU/mL, it was possible to determine the breakpoint of the clinical yeasts by MALDI-TOF that presented high agreement with the clinical laboratory standard institute (CLSI) reference method. Herein, we show that mass spectrometry using the MALDI-TOF technique is powerful when it exploits antifungal susceptibility testing assays.

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