Emergence of clonal fluconazole-resistant Candida parapsilosis clinical isolates in a multicentre laboratory-based surveillance study in India

Singh, Ashutosh; Singh, Pradeep Kumar; Groot, Theun de; Kumar, Anil; Mathur, Purva; Tarai, Bansidhar; Sachdeva, Neelam; Upadhyaya, Gargi; Sarma, Satyam; Meis, Jacques F.; Chowdhary, Anuradha

doi:10.1093/jac/dkz029

Cited by 61 publications

(64 citation statements)

References 47 publications

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“…Furthermore, a Korean single-center study reported a significant increase in the prevalence of FLZR among 2015-2016 isolates when compared to 2011-2015 isolates (14.3% vs. 0.9%, respectively) [184]. Unfortunately, this wave of FLZR C. parapsilosis isolates has also been observed in Kuwait [166], USA [165,185], Brazil [167,168], South Korea [164], India [169], South Africa [182] and Turkey [170]. The high rate of FLZR for a species that used to be susceptible to azoles may have arisen from the disproportionate use of azoles in the hospital [170,182].…”

Section: Candida Parapsilosismentioning

confidence: 99%

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

Arastehfar

Lass‐Flörl

Garcia-Rubio

et al. 2020

JoF

114

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Human fungal pathogens are attributable to a significant economic burden and mortality worldwide. Antifungal treatments, although limited in number, play a pivotal role in decreasing mortality and morbidities posed by invasive fungal infections (IFIs). However, the recent emergence of multidrug-resistant Candida auris and Candida glabrata and acquiring invasive infections due to azole-resistant C. parapsilosis, C. tropicalis, and Aspergillus spp. in azole-naïve patients pose a serious health threat considering the limited number of systemic antifungals available to treat IFIs. Although advancing for major fungal pathogens, the understanding of fungal attributes contributing to antifungal resistance is just emerging for several clinically important MDR fungal pathogens. Further complicating the matter are the distinct differences in antifungal resistance mechanisms among various fungal species in which one or more mechanisms may contribute to the resistance phenotype. In this review, we attempt to summarize the burden of antifungal resistance for selected non-albicansCandida and clinically important Aspergillus species together with their phylogenetic placement on the tree of life. Moreover, we highlight the different molecular mechanisms between antifungal tolerance and resistance, and comprehensively discuss the molecular mechanisms of antifungal resistance in a species level.

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Section: Candida Parapsilosismentioning

confidence: 99%

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

Arastehfar

Lass‐Flörl

Garcia-Rubio

et al. 2020

JoF

114

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“…Resistance may occur in one of the following ways: (a) point mutations in ERG11 gene, resulting in reduced azole binding affinity; (b) overexpression of the drug target ( ERG11 ) gene which encodes for 14α demethylase; (c) overexpression of the genes encoding multidrug transporters [ATP binding cassettes (ABC) and major facilitator superfamily (MFS)]; (d) overexpression of CDR1 and CDR caused by activating mutations in the transcription factor genes TAC1 leading to efflux of all azole antifungal agents 8 ; (e) overexpression of an MFS transporter ( MDR1 ) caused by activating mutations in the transcription factor genes MRR1 leading to efflux of fluconazole and voriconazole 9‐11 ; and (f) mutations in ERG3 gene resulting in the inactivation of sterol desaturase. A number of studies from the United States of America, United Kingdom, Brazil, Portugal, South Korea and India have recently explored the possible mechanisms of azole resistance in C parapsilosis strains 12‐17 . Souza et al (2015) demonstrated that not only does upregulation of MDR1 and amino acid substitutions in ERG11 lead to resistance to fluconazole but upregulation of ERG11 and CDR1 are involved as well 14 .…”

Section: Introductionmentioning

confidence: 99%

Fluconazole‐resistant Candida parapsilosis strains with a Y132F substitution in the ERG11 gene causing invasive infections in a neonatal unit, South Africa

Magobo

Lockhart

Govender

2020

Mycoses

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Summary Introduction The prevalence of azole resistance in C parapsilosis is very low in most parts of the world. However, South Africa has reported an exceptionally high prevalence of azole resistance in C parapsilosis strains isolated from candidaemia cases. We aimed to determine the possible molecular mechanisms of fluconazole resistance in C parapsilosis isolates obtained through surveillance at a large neonatal unit at a South African academic hospital. Methods We sequenced the ERG11 and MRR1 genes of C parapsilosis isolates recovered from cases of neonatal candidemia, followed by microsatellite genotyping. A total of 73 isolates with antifungal susceptibility results were analysed. Results Of these, 57 (78%) were resistant, 11 (15%) susceptible dose‐dependent and 5 (7%) susceptible. The most commonly identified amino acid substitution within the ERG11 gene was Y132F in 68% (39/57) of fluconazole‐resistant isolates and none in susceptible isolates. Three amino acid substitutions (R405K, G583R and A619V) and 1 nucleotide deletion at position 1331 were identified within MRR1 gene in 19 (26%) isolates. Microsatellite genotyping grouped isolates into four clusters (50 isolates). Cluster 1 accounted for 23% (17/73) of all cases, cluster 2 for 22% (16/73), cluster 3 for 14% (10/73) and cluster 4 for 10% (7/73). We found an association between cluster type and fluconazole resistance (P‐value = .004). Isolates harbouring the Y132F substitution were more likely to belong to a cluster than non‐Y132F isolates. Conclusion Fluconazole resistance in C parapsilosis strains from a single South African neonatal unit was associated with cluster type and predominantly driven by Y123F amino acid substitutions in the ERG11 gene.

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“…Associated with these changes have been reports of candidaemia largely clonal outbreaks due to azole‐resistant Candida spp. in critically ill patients …”

Section: Introductionmentioning

confidence: 99%

“…in critically ill patients. [6][7][8][9][10] Because of these issues, the need for sensitive non-culture-based diagnostic assays with improved turnaround times became critical. The 1,3-beta-D-glucan (BDG) is a broad fungal detection antigen which has been used as an adjunct in the diagnosis of invasive fungal infections worldwide for more than a decade with numerous publications illustrating its use in various clinical settings.…”

mentioning

confidence: 99%

Comparative sensitivity of 1,3 beta‐D‐glucan for common causes of candidaemia in South Africa

Fadana

Bosman²,

Nana

2019

Mycoses

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Summary Culture‐based diagnosis of candidaemia suffers poor sensitivity and prolonged turnaround time. The 1,3‐beta‐D‐glucan (BDG) assay is a non‐culture‐based broad fungal antigen with rapid turnaround time. To assess overall, species‐specific and population‐specific sensitivity of the BDG assay for candidaemia, to determine if the BDG assay is able to detect candidaemia prior to blood culture collection, and to evaluate the performance of the assay for the detection of Candida auris candidaemia. A retrospective review of all blood cultures (BC) with C albicans, C parapsilosis, C glabrata, C krusei and C auris was performed. A corresponding BDG result (Fungitell®) within 10 days of the BC was sought on the laboratory information system. Overall sensitivity of the assay was 79% (95% CI 73‐85; 173/218). Per species sensitivity was 81% (95% CI 72‐90; 66/81) for C albicans, 72% (61‐83; 60/83) for C parapsilosis, 90% (95% CI 79‐100; 27/30) for C glabrata, 71% (95% CI 43‐99; 10/14) C auris and 100% (10/10) for C krusei. No statistically significant difference in sensitivity between species was noted (P = .093). The assay demonstrated 92% (59/64) sensitivity in neonatal ICU (P = .047) compared to 94% (15/16) in surgery, 81% (59/73) in adult ICUs and 71% (15/21) in Oncology. BDG results were positive up to 10 days prior to blood culture collection with no significant difference in detection rate (P = .563). BDG results were positive up to 10 days prior to blood culture collection. BDG when collected a mean of 2.5 days (range 1‐10 days) prior to blood culture collection were positive.

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Emergence of clonal fluconazole-resistant Candida parapsilosis clinical isolates in a multicentre laboratory-based surveillance study in India

Cited by 61 publications

References 47 publications

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

Fluconazole‐resistant Candida parapsilosis strains with a Y132F substitution in the ERG11 gene causing invasive infections in a neonatal unit, South Africa

Comparative sensitivity of 1,3 beta‐D‐glucan for common causes of candidaemia in South Africa

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