Candidemia and Death by Candida orthopsilosis and Candida metapsilosis in Neonates and Children

Oliveira, Vanessa Kummer Perinazzo; Paula, Claudete Rodrigues; Colombo, Arnaldo Lopes; Merseguel, Karina Bellinghausen; Nishikaku, Angela Satie; Moreira, Débora Astoni; Ruiz, Luciana da Silva

doi:10.1016/j.pedneo.2013.07.006

Cited by 12 publications

(16 citation statements)

References 5 publications

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“…We assume that such a low level of antifungal resistance in our study might be explained by the lack of previous and prolonged antifungal exposure (Ii et al, 2013;Perlin, 2015) and the fact that prophylactic antifungal therapy is not well-exercised in many Iranian hospitals. Surprisingly, as discussed earlier (Arastehfar et al, 2019b), some patients infected with azole/echinocandin susceptible C. parapsilosis and C. orthopsilosis isolates died despite the use of antifungal therapy, which is in agreement with other studies showing that in both species in-vitro susceptibility does not always correlate with clinical outcome (Choi et al, 2010;Wessel et al, 2013;Dimopoulou et al, 2014;Oliveira et al, 2014). This could be viewed as a multifaceted controversial concept that might arise from the underlying condition of the patients, the potent sequestration of azole and echinocandins by biofilm (Soldini et al, 2018), colonization in tissues inhibiting efficient drug penetration (Zhao et al, 2017), and the synergistic antifungal activity of the immune system (Dimopoulou et al, 2014).…”

Section: Discussionsupporting

confidence: 86%

“…Apart from being less susceptible to echinocandins (Garcia-Effron et al, 2008), fluconazole resistant C. parapsilosis isolates have emerged in India (Singh et al, 2019), South Korea (Choi et al, 2018), Kuwait (Asadzadeh et al, 2017a), USA (Berkow et al, 2015;Grossman et al, 2015), and Brazil (Souza et al, 2015;Thomaz et al, 2018). Additionally, the closely related cryptic species of C. parapsilosis, i.e., C. orthopsilosis, is linked to numerous clinical failures (Wessel et al, 2013;Oliveira et al, 2014;Heslop et al, 2015;Charsizadeh et al, 2018b), and implicated in a wide range of clinical manifestations, including superficial infections (Feng et al, 2012), septic arthritis (Heslop et al, 2015), keratitis (Wessel et al, 2013), and fatal invasive bloodstream infections (Choi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates

Arastehfar

Daneshnia

Najafzadeh

et al. 2020

Front. Cell. Infect. Microbiol.

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Clonal expansion of fluconazole resistant (FLZ-R) Candida parapsilosis isolates is increasingly being identified in many countries, while there is no study exploring the antifungal susceptibility pattern, genetic diversity, and clinical information for Iranian C. parapsilosis blood isolates. Candida parapsilosis species complex blood isolates (n = 98) were recovered from nine hospitals located in three major cities, identified by MALDI-TOF MS, and their genetic relatedness was examined by AFLP fingerprinting. Antifungal susceptibility testing followed CLSI-M27-A3 and ERG11, MRR1 and hotspots 1/2 (HS1/2) of FKS1 were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four C. parapsilosis and four Candida orthopsilosis isolates were identified from 90 patients. Only 43 patients received systemic antifungal drugs with fluconazole as the main antifungal used. The overall mortality rate was 46.6% (42/90) and death mostly occurred for those receiving systemic antifungals (25/43) relative to those not treated (17/47). Although, antifungal-resistance was rare, one isolate was multidrug-resistant (FLZ = 16 µg/ml and micafungin = 8 µg/ml) and the Arastehfar et al. Candida parapsilosis Blood Isolates Typing infected patient showed therapeutic failure to FLZ prophylaxis. Mutations causing azole and echinocandin resistance were not found in the genes studied. AFLP revealed five genotypes (G) and G1 was the main one (59/94; 62.7%). Clinical outcome was significantly associated with city (P = 0.02, α <0.05) and Mashhad was significantly associated with mortality (P = 0.03, α <0.05). Overall, we found a low level of antifungal resistance for Iranian C. parapsilosis blood isolates, but the noted MDR strain can potentially become the source of future infections and challenge the antifungal therapy in antifungal-naïve patients. AFLP typing results warrants confirmation using other resolutive typing methods.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates

Arastehfar

Daneshnia

Najafzadeh

et al. 2020

Front. Cell. Infect. Microbiol.

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“…metapsilosis being the one with the lowest clinical prevalence, and accounting for only 1.1 to 8.4% of the infections caused by the complex [ 13 ]. In addition, the species differ in their degree of prevalence across different types of patients [ 14 – 15 ]. There are few studies investigating the virulence of C .…”

Section: Introductionmentioning

confidence: 99%

The Genomic Aftermath of Hybridization in the Opportunistic Pathogen Candida metapsilosis

et al. 2015

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Candida metapsilosis is a rarely-isolated, opportunistic pathogen that belongs to a clade of pathogenic yeasts known as the C. parapsilosis sensu lato species complex. To gain insight into the recent evolution of C. metapsilosis and the genetic basis of its virulence, we sequenced the genome of 11 clinical isolates from various locations, which we compared to each other and to the available genomes of the two remaining members of the complex: C. orthopsilosis and C. parapsilosis. Unexpectedly, we found compelling genomic evidence that C. metapsilosis is a highly heterozygous hybrid species, with all sequenced clinical strains resulting from the same past hybridization event involving two parental lineages that were approximately 4.5% divergent in sequence. This result indicates that the parental species are non-pathogenic, but that hybridization between them formed a new opportunistic pathogen, C. metapsilosis, that has achieved a worldwide distribution. We show that these hybrids are diploid and we identified strains carrying loci for both alternative mating types, which supports mating as the initial mechanism for hybrid formation. We trace the aftermath of this hybridization at the genomic level, and reconstruct the evolutionary relationships among the different strains. Recombination and introgression -resulting in loss of heterozygosis- between the two subgenomes have been rampant, and includes the partial overwriting of the MTLa mating locus in all strains. Collectively, our results shed light on the recent genomic evolution within the C. parapsilosis sensu lato complex, and argue for a re-definition of species within this clade, with at least five distinct homozygous lineages, some of which having the ability to form hybrids.

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“…orthopsilosis isolates originated from 8 neonates. Only few previous studies have reported the isolation of this species from blood cultures of neonates borne prematurely and young children [ 38 – 40 ].…”

Section: Discussionmentioning

confidence: 99%

Simple, Low-Cost Detection of Candida parapsilosis Complex Isolates and Molecular Fingerprinting of Candida orthopsilosis Strains in Kuwait by ITS Region Sequencing and Amplified Fragment Length Polymorphism Analysis

et al. 2015

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Candida parapsilosis has now emerged as the second or third most important cause of healthcare-associated Candida infections. Molecular studies have shown that phenotypically identified C. parapsilosis isolates represent a complex of three species, namely, C. parapsilosis, C. orthopsilosis and C. metapsilosis. Lodderomyces elongisporus is another species phenotypically closely related to the C. parapsilosis-complex. The aim of this study was to develop a simple, low cost multiplex (m) PCR assay for species-specific identification of C. parapsilosis complex isolates and to study genetic relatedness of C. orthopsilosis isolates in Kuwait. Species-specific amplicons from C. parapsilosis (171 bp), C. orthopsilosis (109 bp), C. metapsilosis (217 bp) and L. elongisporus (258 bp) were obtained in mPCR. Clinical isolates identified as C. parapsilosis (n = 380) by Vitek2 in Kuwait and an international collection of 27 C. parapsilosis complex and L. elongisporus isolates previously characterized by rDNA sequencing were analyzed to evaluate mPCR. Species-specific PCR and DNA sequencing of internal transcribed spacer (ITS) region of rDNA were performed to validate the results of mPCR. Fingerprinting of 19 clinical C. orthopsilosis isolates (including 4 isolates from a previous study) was performed by amplified fragment length polymorphism (AFLP) analysis. Phenotypically identified C. parapsilosis isolates (n = 380) were identified as C. parapsilosis sensu stricto (n = 361), C. orthopsilosis (n = 15), C. metapsilosis (n = 1) and L. elongisporus (n = 3) by mPCR. The mPCR also accurately detected all epidemiologically unrelated C. parapsilosis complex and L. elongisporus isolates. The 19 C. orthopsilosis isolates obtained from 16 patients were divided into 3 haplotypes based on ITS region sequence data. Seven distinct genotypes were identified among the 19 C. orthopsilosis isolates by AFLP including a dominant genotype (AFLP1) comprising 11 isolates recovered from 10 patients. A rapid, low-cost mPCR assay for detection and differentiation of C. parapsilosis, C. orthopsilosis, C. metapsilosis and L. elongisporus has been developed.

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Candidemia and Death by Candida orthopsilosis and Candida metapsilosis in Neonates and Children

Cited by 12 publications

References 5 publications

Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates

Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates

The Genomic Aftermath of Hybridization in the Opportunistic Pathogen Candida metapsilosis

Simple, Low-Cost Detection of Candida parapsilosis Complex Isolates and Molecular Fingerprinting of Candida orthopsilosis Strains in Kuwait by ITS Region Sequencing and Amplified Fragment Length Polymorphism Analysis

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