Cryptic and Rare Aspergillus Species in Brazil: Prevalence in Clinical Samples and
            <i>In Vitro</i>
            Susceptibility to Triazoles

Negri, Clara E; Gonçalves, Sarah Santos; Xafranski, Hemílio; Bergamasco, Maria Daniela; Aquino, Valério Rodrigues; Castro, P. T. O.; Colombo, Arnaldo Lopes

doi:10.1128/jcm.01582-14

Cited by 78 publications

(57 citation statements)

References 28 publications

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“…This is in contrast to reports from Europe and the United States, where the most frequently identified rare Aspergillus species belonged to the section Flavi, followed by Nigri, Usti, and Fumigati (8,9). However, in Brazil, Aspergillus species belonging to the section Flavi were most commonly reported, followed by Nidulantes (29). Considering that in the present study, only a limited number of isolates from the collection of Aspergillus species were molecularly identified, this may not represent the true scenario of the species and sections distribution.…”

Section: Discussioncontrasting

confidence: 54%

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

et al. 2016

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dAspergillus species cause a wide spectrum of clinical infections. Although Aspergillus fumigatus and Aspergillus flavus remain the most commonly isolated species in aspergillosis, in the last decade, rare and cryptic Aspergillus species have emerged in diverse clinical settings. The present study analyzed the distribution and in vitro antifungal susceptibility profiles of rare Aspergillus species in clinical samples from patients with suspected aspergillosis in 8 medical centers in India. Further, a matrix-assisted laser desorption ionization-time of flight mass spectrometry in-house database was developed to identify these clinically relevant Aspergillus species. ␤-Tubulin and calmodulin gene sequencing identified 45 rare Aspergillus isolates to the species level, except for a solitary isolate. They included 23 less common Aspergillus species belonging to 12 sections, mainly in Circumdati, Nidulantes, Flavi, Terrei, Versicolores, Aspergillus, and Nigri. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified only 8 (38%) of the 23 rare Aspergillus isolates to the species level. Following the creation of an in-house database with the remaining 14 species not available in the Bruker database, the MALDI-TOF MS identification rate increased to 95%. Overall, high MICs of >2 g/ml were noted for amphotericin B in 29% of the rare Aspergillus species, followed by voriconazole in 20% and isavuconazole in 7%, whereas MICs of >0.5 g/ml for posaconazole were observed in 15% of the isolates. Regarding the clinical diagnoses in 45 patients with positive rare Aspergillus species cultures, 19 (42%) were regarded to represent colonization. In the remaining 26 patients, rare Aspergillus species were the etiologic agent of invasive, chronic, and allergic bronchopulmonary aspergillosis, allergic fungal rhinosinusitis, keratitis, and mycetoma.A spergillus species cause a wide spectrum of clinical infections, ranging from allergic to chronic and life-threatening invasive diseases (1). The most common pathogenic species implicated in aspergillosis are A. fumigatus, A. flavus, A. terreus, and rarely, A. niger. However, in the last decade, several reports have pointed to a shift in the etiology of aspergillosis and highlighted the emergence of cryptic and rare Aspergillus species in various clinical settings in both immunocompromised and immunocompetent hosts (2-4). This shift is mainly linked to the application of multilocus DNA sequence analysis in various studies, leading to the description of previously unknown "cryptic" Aspergillus species (5-7). In two population-based prospective studies in the United States and Spain, the prevalences of cryptic Aspergillus species detected in clinical specimens were found to be 10% and 12%, respectively (8, 9). The molecular analysis of aspergilli collected from the Transplant-Associated Infection Surveillance Network (TRANSNET) from 24 transplant centers throughout the United States revealed that 10% of the isolates associated with invasive aspe...

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Section: Discussioncontrasting

confidence: 54%

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

et al. 2016

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“…Although their role as etiologic agents in these cases is unknown, detection of 34 isolates of this section over a period of 12 years in a single reference center, together with some reports on infections produced by members of this section in the same period (15,17,18,22,27), highlights the importance of these fungi in the clinical setting. The degree of morphological similarity among the species of the Circumdati section, as with other groups of Aspergillus, requires DNA sequencing analysis for a definitive identification.…”

Section: Discussionmentioning

confidence: 99%

“…Several species in this section have been involved in different types of infections, such as onychomycosis, caused by A. insulicola, A. melleus, A. ochraceopetaliformis, A. persii, A. sclerotiorum, and A. westerdijkiae (9)(10)(11)(12)(13)(14); otomycosis, caused by A. sclerotiorum (15); skin infection, caused by A. westerdijkiae (12); and pulmonary aspergillosis and osteomyelitis, caused by A. ochraceus (16,17). Moreover, A. ochraceus, A. sclerotiorum, and A. westerdijkiae have been repetitively isolated from clinical specimens of immunocompromised patients, although in such cases their pathogenic role is uncertain (18)(19)(20)(21)(22).…”

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confidence: 99%

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

et al. 2017

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A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the United States and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were the internal transcribed spacer (ITS) region, and fragments of the beta-tubulin (BenA), calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) genes. The drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A. pseudosclerotiorum (23.5%). Other species identified were A. sclerotiorum (17.6%), A. ochraceus (8.8%), A. subramanianii (8.8%), and A. insulicola and A. ochraceopetaliformis, with two isolates (5.9%) of each. The drugs that showed the most potent activity were caspofungin, micafungin, and terbinafine, while amphotericin B showed the least activity.KEYWORDS Aspergillus, Circumdati section, clinical isolates, molecular identification, phenotypic identification S ection Circumdati includes aspergilli with biseriate conidial heads in shades of yellow to ochre, with mostly globose vesicles, and sclerotia variable in shape and color (1-3). It contains 26 species (3), with A. ochraceus being the best known and described as an important producer of many extrolites, including the mycotoxin ochratoxin A (3-5). This metabolite has nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties (6, 7) and is commonly found in coffee, rice, beverages, and other contaminated foodstuffs (3,8). Several species in this section have been involved in different types of infections, such as onychomycosis, caused by A. insulicola, A. melleus, A. ochraceopetaliformis, A. persii, A. sclerotiorum, and A. westerdijkiae (9-14); otomycosis, caused by A. sclerotiorum (15); skin infection, caused by A. westerdijkiae (12); and pulmonary aspergillosis and osteomyelitis, caused by A. ochraceus (16,17). Moreover, A. ochraceus, A. sclerotiorum, and A. westerdijkiae have been repetitively isolated from clinical specimens of immunocompromised patients, although in such cases their pathogenic role is uncertain (18)(19)(20)(21)(22).There are few data on the in vitro antifungal susceptibility of species within section Circumdati. The azoles, especially itraconazole, appear to have good activity against A.

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“…Despite being highly effective against Aspergillus spp., resistance to azoles is becoming an emerging health problem in some parts of the world (7,8). Two scenarios related to the emergence of azole resistance are the increasing number of non-fumigatus Aspergillus species, such as A. lentulus and A. calidoustus, with primary resistance to triazoles, thus causing human infections (9)(10)(11); and the development of secondary resistance in A. fumigatus isolates after environmental or human exposure to triazoles (12)(13)(14)(15)(16). Indeed, acquisition of resistant A. fumigatus isolates selected by environmental exposition to triazole fungicides in agriculture was recently reported in 1.7% to 30% of all clinical isolates cultured in medical centers in The Netherlands (16)(17)(18)(19)(20).…”

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confidence: 99%

“…The clinical specimens included sputum (n ϭ 73; 33%), tracheal aspirates (n ϭ 24; 10.9%), bronchoalveolar lavage (n ϭ 39; 17.6%), lung and nasal biopsy samples (n ϭ 18; 8.1%), and others (n ϭ 67; 30.3%). All isolates were identified by calmodulin, ␤-tubulin genes, and ribosomal DNA (rDNA) internal transcribed spacer region sequencing (9,24). Antifungal susceptibility tests were performed in duplicate according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 protocol for itraconazole (ITC), voriconazole (VRC), and posaconazole (PSC) (25).…”

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confidence: 99%

Triazole Resistance Is Still Not Emerging in Aspergillus fumigatus Isolates Causing Invasive Aspergillosis in Brazilian Patients

Negri

Gonçalves

Sousa

et al. 2017

Antimicrob Agents Chemother

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Aspergillus fumigatus azole resistance has emerged as a global health problem. We evaluated the in vitro antifungal susceptibility of 221 clinical A. fumigatus isolates according to CLSI guidelines. Sixty-one isolates exhibiting MICs at the epidemiological cutoff value (ECV) for itraconazole or above the ECV for any triazole were checked for CYP51A mutations. No mutations were documented, even for the isolates (1.8%) with high voriconazole MICs, indicating that triazoles may be used safely to treat aspergillosis in Brazil.

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Cryptic and Rare Aspergillus Species in Brazil: Prevalence in Clinical Samples and In Vitro Susceptibility to Triazoles

Cited by 78 publications

References 28 publications

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

Identification by Molecular Methods and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and Antifungal Susceptibility Profiles of Clinically Significant Rare Aspergillus Species in a Referral Chest Hospital in Delhi, India

Multilocus Phylogeny and Antifungal Susceptibility of Aspergillus Section Circumdati from Clinical Samples and Description of A. pseudosclerotiorum sp. nov

Triazole Resistance Is Still Not Emerging in Aspergillus fumigatus Isolates Causing Invasive Aspergillosis in Brazilian Patients

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