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Published By Oxford University Press

1460-2709, 1369-3786

2021 ◽  
Author(s):  
Ali S Omrani ◽  
Junais Koleri ◽  
Fatma Ben Abid ◽  
Joanne Daghfal ◽  
Thasneem Odaippurath ◽  
...  

2021 ◽  
Author(s):  
Rashi Verma ◽  
Dibyabhaba Pradhan ◽  
Ziaul Hasan ◽  
Harpreet Singh ◽  
Arun Kumar Jain ◽  
...  

Abstract The emergence of antifungal drug resistance in Candida species has led to increased morbidity and mortality in immunocompromised patients. Understanding species distribution and antifungal drug resistance patterns is an essential step for novel drug development. A systematic review was performed addressing this challenge in India with keywords inclusive of ‘Candida’, ‘Antifungal Drug Resistance’, ‘Candidemia’, ‘Candidiasis’ and ‘India’. A total of 106 studies (January 1978-March 2020) from 20 Indian states were included. Of over 11,429 isolates, Candida albicans was the major species accounting for 37.95% of total isolates followed by C. tropicalis (29.40%), C. glabrata (11.68%) and C. parapsilosis (8.36%). Rates of antifungal resistance were highest in non-albicans Candida (NAC) species - C. haemuloni (47.16%), C. krusei (28.99%), C. lipolytica (28.89%) and C. glabrata (20.69%). Approximately 10.34% isolates of C. albicans were observed to be drug-resistant. Candida species were frequently resistant to certain azoles (ketoconazole-22.2%, miconazole–22.1% and fluconazole–21.8%). In conclusion, the present systematic review illustrates the overall distribution and antifungal resistance pattern of Candida species among the Indian population that could be helpful in the future for the formation of treatment recommendations for the region but also elsewhere.


2021 ◽  
Author(s):  
Ali S Omrani ◽  
Junais Koleri ◽  
Fatma Ben Abid ◽  
Joanne Daghfel ◽  
Thasneem Odaippurath ◽  
...  

Abstract Patients with COVID-19-associated candidemia (CAC) in an intensive care unit (ICU) were matched 1:2 with those without candidemia, based on ICU admission date and length of stay in ICU being at least equal to that before candidemia in the corresponding case. The incidence rate of CAC was 2.34 per 1,000 ICU days. Eighty cases could be matched to appropriate controls. In the multivariate conditional logistic regression analysis, age (P 0.001), and sequential organ failure assessment score (P 0.046) were the only risk factors independently associated with CAC. Tocilizumab and corticosteroids therapy were not independently associated with candidemia. Lay Summary In COVID-19 patients who need medical care in an intensive care unit, the risk of developing bloodstream Candida infection is higher in older patients and in those who have a more severe critical illness. Treatment with steroids or tocilizumab does not seem to affect the risk of candida bloodstream infection in these patients.


2021 ◽  
Author(s):  
Daiana Macedo ◽  
Florencia Leonardelli ◽  
Matias S Cabeza ◽  
Soledad Gamarra ◽  
Guillermo Garcia-Effron

Abstract Rhizopus oryzae (heterotypic synonym: R. arrhizus) intrinsic voriconazole and fluconazole resistance has been linked to its CYP51A gene. However, the amino acid residues involved in this phenotype have not yet been established. A comparison between R. oryzae and Aspergillus fumigatus Cyp51Ap sequences showed differences in several amino acid residues. Some of them were already linked with voriconazole resistance in A. fumigatus. The objective of this work was to analyze the role of two natural polymorphisms in the intrinsic voriconazole resistance phenotype of R. oryzae (Y129F and T290A, equivalent to Y121F and T289A seen in triazole-resistant A. fumigatus). We have generated A. fumigatus chimeric strains harboring different R. oryzae CYP51A genes (wild-type and mutants). These mutant R. oryzae CYP51A genes were designed to carry nucleotide changes that produce mutations at Cyp51Ap residues 129 and 290 (emulating the Cyp51Ap protein of azole susceptible A. fumigatus). Antifungal susceptibilities were evaluated for all the obtained mutants. The polymorphism T290A (alone or in combination with Y129F) had no impact on triazole MIC. On the other hand, a > 8-fold decrease in voriconazole MICs was observed in A. fumigatus chimeric strains harboring the RoCYP51Ap-F129Y. This phenotype supports the assumption that the naturally occurring polymorphism Y129F at R. oryzae Cyp51Ap is responsible for its voriconazole resistance phenotype. In addition, these chimeric mutants were posaconazole hypersusceptible. Thus, our experimental data demonstrate that the RoCYP51Ap-F129 residue strongly impacts VRC susceptibility and that it would be related with posaconazole-RoCYP51Ap interaction. Lay summary Rhizopus oryzae is intrinsically resistant to voriconazole, a commonly used antifungal agent. In this work, we analyze the role of two natural polymorphisms present in the target of azole drugs. We established that F129 residue is responsible of the intrinsic voriconazole resistance in this species.


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