About the Authors: Anuradha Chowdhary * E-mail: dranuradha@hotmail.com Affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India ORCID ...http://orcid.org/0000-0002-2028-7462 Cheshta Sharma Affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India Jacques F. Meis Affiliations Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands, Centre of Expertise in Mycology Radboudumc/CWZ, Nijmegen, the Netherlands ORCID http://orcid.org/0000-0003-3253-6080Citation: Chowdhary A, Sharma C, Meis JF (2017) Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. The species exhibits a close phylogenetic relationship to C. haemulonii and is differentiated based on sequence analysis of the D1/D2 domain of the large ribosomal subunit (LSU) of 26S rRNA gene and the internal transcribed spacer (ITS) regions of the nuclear rRNA gene operon 23. ...Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is considered a more rapid and robust diagnostic technique for C. auris identification 9, 10, 13, 16. Worldwide reports of Candida auris along with their misidentification using commercial systems and frequency of antifungal resistance. https://doi.org/10.1371/journal.ppat.1006290.t001 Does genetic predisposition make C. auris virulent? A recently published draft genome of C. auris shows that it has a genome size of approximately 12.3 Mb 26, 27. The emerging Candida auris: characterization of growth phenotype, virulence factors, antifungal activity, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation. Identification and typing of the emerging pathogen Candida auris by matrix-assisted laser desorption ionisation time of flight mass spectrometry...
...50% of the patients with invasive aspergillosis due to ARAF are known to be azole naïve and the outcome of patients with azole-resistant invasive aspergillosis has been dismal, with a mortality ...rate of 88% 12. ...it would be beneficial to (i) have an active multi-azole susceptibility testing of A. fumigatus to monitor the extent of the problem, (ii) reduce agricultural use of triazole DMI fungicides, and (iii) use combination drug therapy when dealing with infections by A. fumigatus strains to limit the emergence of resistance.
Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and ...fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis. Lately, increased azole resistance in A. fumigatus has become a significant challenge in effective management of aspergillosis. Earlier studies have brought to light the contribution of non-cyp51 mutations along with alterations in cyp51A gene resulting in azole-resistant phenotypes of A. fumigatus. This review highlights the magnitude of azole-resistant aspergillosis and resistance mechanisms implicated in the development of azole-resistant A. fumigatus and address the therapeutic options available.
Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the ...other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.
In their Article4 in The Lancet Infectious Diseases, investigators from the CDC and the US Candida auris Investigation Team alert readers to the introduction and widespread, ongoing transmission in ...US health facilities of C auris. The drivers of the emergence of C auris in the last decade are, at present, elusive, but human demographics, extensive empirical fluconazole use in intensive care facilities, and poor infection control, combined with international travel, globalisation, and medical tourism are the most likely factors to be associated with the ongoing outbreaks. The stringent recognition of the problem and simultaneous implementation of precautions to prevent the spread of C auris among patients should be taken as seriously as in bacterial pathogens. iStock/Dr_Microbe JFM reports grants from F2G and Merck, he has been a consultant to SCYNEXIS and Merck, and he reports speakers' fees from Merck, United Medical, Teva Pharmaceutical Industries, and Gilead Sciences.
Azole resistance is an emerging problem in Aspergillus which impacts the management of aspergillosis. Here in we report the emergence and clonal spread of resistance to triazoles in environmental ...Aspergillus fumigatus isolates in India. A total of 44 (7%) A. fumigatus isolates from 24 environmental samples were found to be triazole resistant. The isolation rate of resistant A. fumigatus was highest (33%) from soil of tea gardens followed by soil from flower pots of the hospital garden (20%), soil beneath cotton trees (20%), rice paddy fields (12.3%), air samples of hospital wards (7.6%) and from soil admixed with bird droppings (3.8%). These strains showed cross-resistance to voriconazole, posaconazole, itraconazole and to six triazole fungicides used extensively in agriculture. Our analyses identified that all triazole-resistant strains from India shared the same TR(34)/L98H mutation in the cyp51 gene. In contrast to the genetic uniformity of azole-resistant strains the azole-susceptible isolates from patients and environments in India were genetically very diverse. All nine loci were highly polymorphic in populations of azole-susceptible isolates from both clinical and environmental samples. Furthermore, all Indian environmental and clinical azole resistant isolates shared the same multilocus microsatellite genotype not found in any other analyzed samples, either from within India or from the Netherlands, France, Germany or China. Our population genetic analyses suggest that the Indian azole-resistant A. fumigatus genotype was likely an extremely adaptive recombinant progeny derived from a cross between an azole-resistant strain migrated from outside of India and a native azole-susceptible strain from within India, followed by mutation and then rapid dispersal through many parts of India. Our results are consistent with the hypothesis that exposure of A. fumigatus to azole fungicides in the environment causes cross-resistance to medical triazoles. The study emphasises the need of continued surveillance of resistance in environmental and clinical A. fumigatus strains.
Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised ...concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
Candida auris is a multidrug-resistant yeast that causes a wide spectrum of infections, especially in intensive care settings. We investigated C. auris prevalence among 102 clinical isolates ...previously identified as Candida haemulonii or Candida famata by the Vitek 2 system. Internal transcribed spacer region (ITS) sequencing confirmed 88.2% of the isolates as C. auris, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) easily separated all related species, viz., C. auris (n = 90), C. haemulonii (n = 6), C. haemulonii var. vulnera (n = 1), and Candida duobushaemulonii (n = 5). The in vitro antifungal susceptibility was determined using CLSI broth microdilution (CLSI-BMD), the Vitek 2 antifungal susceptibility test, and the Etest method. C. auris isolates revealed uniformly elevated fluconazole MICs (MIC50, 64 μg/ml), and an alarming percentage of isolates (37%) exhibited elevated caspofungin MICs by CLSI-BMD. Notably, 34% of C. auris isolates had coexisting elevated MICs (≥2 μg/ml) for both fluconazole and voriconazole, and 10% of the isolates had elevated coexisting MICs (≥2 μg/ml) to two additional azoles, i.e., posaconazole and isavuconazole. In contrast to reduced amphotericin B MICs by CLSI-BMD (MIC50, 1 μg/ml) for C. auris, elevated MICs were noted by Vitek 2 (MIC50, 8 μg/ml), which were statistically significant. Candida auris remains an unnoticed pathogen in routine microbiology laboratories, as 90% of the isolates characterized by commercial identification systems are misidentified as C. haemulonii. MALDI-TOF MS proved to be a more robust diagnostic technique for rapid identification of C. auris. Considering that misleading elevated MICs of amphotericin B by the Vitek AST-YS07 card may lead to the selection of inappropriate therapy, a cautionary approach is recommended for laboratories relying on commercial systems for identification and antifungal susceptibility testing of rare yeasts.
After 1960, the increasing use of antibiotics became a major predisposing condition 4. Since 1970, prolonged neutropenia due to intensified cytotoxic treatment of hematologic malignancies was the ...leading risk factor in novel types of fusariosis 5. Since 1980, Fusarium infections have been seen in severely immunocompromised patients with a 100% mortality rate, e.g., in cases of cerebral involvement 6. To date, about 36 of the alleged human opportunists carry a name, while 38 are still unnamed and can only be identified by multilocus sequence analysis (MLSA). ...far, 21 species have been described with proven case reports 16, and more have been published in the literature.