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

2017 ◽  
Vol 55 (3) ◽  
pp. 947-958 ◽  
Author(s):  
J. P. Z. Siqueira ◽  
D. A. Sutton ◽  
J. Gené ◽  
D. García ◽  
N. Wiederhold ◽  
...  

ABSTRACTA multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates fromAspergillussectionCircumdatifrom the United States and to determine theirin vitroantifungal 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 wasA. westerdijkiae(29.4%), followed by a novel species, which was described here asA. pseudosclerotiorum(23.5%). Other species identified wereA. sclerotiorum(17.6%),A. ochraceus(8.8%),A. subramanianii(8.8%), andA. insulicolaandA. 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.

2016 ◽  
Vol 54 (8) ◽  
pp. 2155-2161 ◽  
Author(s):  
Marcela Guevara-Suarez ◽  
Deanna A. Sutton ◽  
José F. Cano-Lira ◽  
Dania García ◽  
Adela Martin-Vicente ◽  
...  

Penicilliumspecies are some of the most common fungi observed worldwide and have an important economic impact as well as being occasional agents of human and animal mycoses. A total of 118 isolates thought to belong to the genusPenicilliumbased on morphological features were obtained from the Fungus Testing Laboratory at the University of Texas Health Science Center in San Antonio (United States). The isolates were studied phenotypically using standard growth conditions. Molecular identification was made using two genetic markers, the internal transcribed spacer (ITS) and a fragment of the β-tubulin gene. In order to assess phylogenetic relationships, maximum likelihood and Bayesian inference assessments were used. Antifungal susceptibility testing was performed according to CLSI document M38-A2 for nine antifungal drugs. The isolates were identified within three genera, i.e.,Penicillium,Talaromyces, andRasamsonia. The most frequent species in our study werePenicillium rubens,P. citrinum, andTalaromyces amestolkiae. The potentin vitroactivity of amphotericin B (AMB) and terbinafine (TRB) and of the echinocandins againstPenicilliumandTalaromycesspecies might offer a good therapeutic alternative for the treatment of infections caused by these fungi.


Author(s):  
Hamid Badali ◽  
Connie Cañete-Gibas ◽  
Dora McCarthy ◽  
Hoja Patterson ◽  
Carmita Sanders ◽  
...  

The global incidence of mucormycosis has increased in recent years owing to higher numbers of individuals at risk for these infections. The diagnosis and treatment of this aggressive fungal infection are of clinical concern due to differences in species distribution in different geographic areas and susceptibility profiles between different species that are capable of causing highly aggressive infections. The purpose of this study was to evaluate the epidemiology and susceptibility profiles of Mucorales isolates in the U.S. over a 52-month period. Species identification was performed by combined phenotypic characteristics and DNA sequence analysis, and antifungal susceptibility testing was performed by CLSI M38 broth microdilution for amphotericin B, isavuconazole, itraconazole, and posaconazole. During this time-frame, 854 isolates were included, representing 11 different genera and over 26 species, of which Rhizopus (58.6%) was the predominant genus followed by Mucor (19.6%). The majority of isolates were cultured from the upper and lower respiratory tracts (55%). Amphotericin B demonstrated the most potent in vitro activity, with GM MICs of ≤0.25 μg/mL against all genera with the exception of Cunninghamella species (GM MIC 1.30 μg/mL). In head-to-head comparisons the most active azole was posaconazole followed by isavuconazole. Differences in azole and amphotericin B susceptibility patterns were observed between the genera with the greatest variability observed with isavuconazole. Awareness of the epidemiology of Mucorales isolates and differences in antifungal susceptibility patterns in the U.S. may aide clinicians in choosing antifungal treatment regimens. Further studies are warranted to correlate these findings with clinical outcomes.


2018 ◽  
Vol 62 (5) ◽  
pp. e02315-17 ◽  
Author(s):  
S. Imbert ◽  
A. C. Normand ◽  
S. Ranque ◽  
J. M. Costa ◽  
J. Guitard ◽  
...  

ABSTRACTAspergillussectionTerreiis a species complex currently comprised of 14 cryptic species whose prevalence in clinical samples as well as antifungal susceptibility are poorly known. The aims of this study were to investigateA. Terreiclinical isolates at the species level and to perform antifungal susceptibility analyses by reference and commercial methods. Eighty-two clinicalA. Terreiisolates were collected from 8 French university hospitals. Molecular identification was performed by sequencing parts of beta-tubulin and calmodulin genes. MICs or minimum effective concentrations (MECs) were determined for 8 antifungal drugs using both EUCAST broth microdilution (BMD) methods and concentration gradient strips (CGS). Among the 79A. Terreiisolates,A. terreus stricto sensu(n= 61),A. citrinoterreus(n= 13),A. hortai(n= 3), andA. alabamensis(n= 2) were identified. All strains had MICs of ≥1 mg/liter for amphotericin B, except for two isolates (bothA. hortai) that had MICs of 0.25 mg/liter. FourA. terreusisolates were resistant to at least one azole drug, including one with pan-azole resistance, yet no mutation in theCYP51Agene was found. All strains had low MECs for the three echinocandins. The essential agreements (EAs) between BMD and CGS were >90%, except for those of amphotericin B (79.7%) and itraconazole (73.4%). Isolates belonging to theA. sectionTerreiidentified in clinical samples show wider species diversity beyond the knownA. terreus sensu stricto. Azole resistance inside the sectionTerreiis uncommon and is not related to CYP51A mutations here. Finally, CGS is an interesting alternative for routine antifungal susceptibility testing.


2016 ◽  
Vol 54 (10) ◽  
pp. 2491-2497 ◽  
Author(s):  
J. P. Z. Siqueira ◽  
D. Sutton ◽  
J. Gené ◽  
D. García ◽  
M. Guevara-Suarez ◽  
...  

Schizophyllumis an important genus of basidiomycetes that, apart from being of genetic and biotechnological interest, is also reported to be a plant and animal pathogen.Schizophyllum communeis the best-known species and the only one reported from clinical specimens thus far, being recovered mainly from the respiratory tract. The aim of this study was to determine the species diversity of 23 clinical isolates ofSchizophyllumfrom the United States using multilocus phylogenetic analysis and theirin vitrosusceptibilities to six drugs. The markers used for sequencing were the internal transcribed spacer (ITS), a portion of the nuclear large subunit (LSU) of ribosomal DNA, the RNA polymerase II second-largest subunit (RPB2), and the translation elongation factor 1α (EF-1α) gene. The analyses revealed that 22 of the clinical isolates were in theSchizophyllum radiatumclade with high support values and 1 isolate was in theS. communeclade. This is the first report of this species in clinical samples. The two species mentioned above showed very similar morphological features in culture (i.e., white, cottony, unsporulated colonies composed of hyphae with clamp connections), making morphological discrimination between the two impossible. An epitype is designed forS. radiatum, and its sequences have been deposited in GenBank. The antifungal that showed the greatestin vitroactivity against the strains tested was shown to be amphotericin B. In general, the strains ofS. radiatumshowed higher MICs thanS. commune.


2012 ◽  
Vol 56 (11) ◽  
pp. 6044-6047 ◽  
Author(s):  
Peiying Feng ◽  
M. Javad Najafzadeh ◽  
Jiufeng Sun ◽  
Sarah Ahmed ◽  
Liyan Xi ◽  
...  

ABSTRACTCyphellophora guyanensis(n= 15), otherCyphellophoraspecies (n= 11),Phialophora europaea(n= 43), and otherPhialophoraspecies (n= 12) were testedin vitroagainst nine antifungal drugs. The MIC90s across all of the strains (n= 81) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.5 μg/ml; voriconazole, 1 μg/ml; micafungin, 1 μg/ml; terbinafine, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 4 μg/ml; fluconazole, 8 μg/ml; amphotericin B, 16 μg/ml.


2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Lysett Wagner ◽  
Sybren de Hoog ◽  
Ana Alastruey-Izquierdo ◽  
Kerstin Voigt ◽  
Oliver Kurzai ◽  
...  

ABSTRACTRecently, the species concept of opportunisticMucor circinelloidesand its relatives has been revised, resulting in the recognition of its classical formae as independent species and the description of new species. In this study, we used isolates of all clinically relevantMucorspecies and performed susceptibility testing using the EUCAST reference method to identify potential species-specific susceptibility patterns.In vitrosusceptibility profiles of 101 mucoralean strains belonging to the genusMucor(72), the closely related speciesCokeromyces recurvatus(3),Rhizopus(12),Lichtheimia(10), andRhizomucor(4) to six antifungals (amphotericin B, natamycin, terbinafine, isavuconazole, itraconazole, and posaconazole) were determined. The most active drug for all Mucorales was amphotericin B. Antifungal susceptibility profiles of pathogenicMucorspecies were specific for isavuconazole, itraconazole, and posaconazole. The species formerly united inM. circinelloidesshowed clear differences in their antifungal susceptibilities.Cokeromyces recurvatus,Mucor ardhlaengiktus,Mucor lusitanicus(M. circinelloidesf.lusitanicus), andMucor ramosissimusexhibited high MICs to all azoles tested.Mucor indicuspresented high MICs for isavuconazole and posaconazole, andMucor amphibiorumandMucor irregularisshowed high MICs for isavuconazole. MIC values ofMucorspp. for posaconazole, isavuconazole, and itraconazole were high compared to those forRhizopusand the Lichtheimiaceae (LichtheimiaandRhizomucor). Molecular identification combined within vitrosusceptibility testing is recommended forMucorspecies, especially if azoles are applied in treatment.


2016 ◽  
Vol 55 (2) ◽  
pp. 552-567 ◽  
Author(s):  
Nicomedes Valenzuela-Lopez ◽  
Deanna A. Sutton ◽  
José F. Cano-Lira ◽  
Katihuska Paredes ◽  
Nathan Wiederhold ◽  
...  

ABSTRACTHuman infections by coelomycetous fungi are becoming more frequent and range from superficial to systemic dissemination. Traumatic implantation of contaminated plant material is the most common cause. The typical morphological feature of these fungi is the production of asexual spores (conidia) within fruiting bodies called conidiomata. This study aimed to determine the distribution of the coelomycetes in clinical samples by a phenotypic and molecular study of a large set of isolates received from a U.S. reference mycological institution and by obtaining thein vitroantifungal susceptibility pattern of nine antifungals against a selected group of isolates. A total of 230 isolates were identified by sequencing the D1 and D2 domains of the large subunit (LSU) nuclear ribosomal RNA (nrRNA) gene and by morphological characterization. Eleven orders of the phylumAscomycotawere identified:Pleosporales(the largest group; 66.1%),Botryosphaeriales(19.57%),Glomerellales(4.35%),Diaporthales(3.48%),Xylariales(2.17%),HysterialesandValsariales(0.87%), andCapnodiales,Helotiales,HypocrealesandMagnaporthales(0.43% each). The most prevalent species wereNeoscytalidium dimidiatum,Paraconiothyriumspp.,Phoma herbarum,Didymella heteroderae, andEpicoccum sorghinum. The most common anatomical site of isolation was superficial tissue (66.5%), followed by the respiratory tract (17.4%). Most of the isolates tested were susceptible to the majority of antifungals, and only flucytosine showed poor antifungal activity.


2015 ◽  
Vol 59 (9) ◽  
pp. 5827-5829 ◽  
Author(s):  
Magdalena Skóra ◽  
Małgorzata Bulanda ◽  
Tomasz Jagielski

ABSTRACTThein vitroactivities of 11 antifungal drugs against 68ScopulariopsisandMicroascusstrains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 μg/ml and 0.125 to 16 μg/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC50and MEC50were 1 µg/ml for both drugs, whereas the MIC90and MEC90were 4 µg/ml and 16 µg/ml, respectively.


2017 ◽  
Vol 55 (6) ◽  
pp. 1812-1820 ◽  
Author(s):  
Tsidiso G. Maphanga ◽  
Erika Britz ◽  
Thokozile G. Zulu ◽  
Ruth S. Mpembe ◽  
Serisha D. Naicker ◽  
...  

ABSTRACTDisseminated emmonsiosis is an important AIDS-related mycosis in South Africa that is caused byEmergomycesafricanus, a newly described and renamed dimorphic fungal pathogen.In vitroantifungal susceptibility data can guide management. Identification of invasive clinical isolates was confirmed phenotypically and by sequencing of the internal transcribed spacer region. Yeast and mold phase MICs of fluconazole, voriconazole, itraconazole, posaconazole, caspofungin, anidulafungin, micafungin, and flucytosine were determined with custom-made frozen broth microdilution (BMD) panels in accordance with Clinical and Laboratory Standards Institute recommendations. MICs of amphotericin B, itraconazole, posaconazole, and voriconazole were determined by Etest. Fifty uniqueE. africanusisolates were tested. The yeast and mold phase geometric mean (GM) BMD and Etest MICs of itraconazole were 0.01 mg/liter. The voriconazole and posaconazole GM BMD MICs were 0.01 mg/liter for both phases, while the GM Etest MICs were 0.001 and 0.002 mg/liter, respectively. The fluconazole GM BMD MICs were 0.18 mg/liter for both phases. The GM Etest MICs of amphotericin B, for the yeast and mold phases were 0.03 and 0.01 mg/liter. The echinocandins and flucytosine had very limitedin vitroactivity. Treatment and outcome data were available for 37 patients; in a multivariable model including MIC data, only isolation from blood (odds ratio [OR], 8.6; 95% confidence interval [CI], 1.3 to 54.4;P= 0.02) or bone marrow (OR, 12.1; 95% CI, 1.2 to 120.2;P= 0.03) (versus skin biopsy) was associated with death.In vitrosusceptibility data support the management of disseminated emmonsiosis with amphotericin B, followed by itraconazole, voriconazole, or posaconazole. Fluconazole was a relatively less potent agent.


2012 ◽  
Vol 57 (3) ◽  
pp. 1275-1282 ◽  
Author(s):  
Francesca Bugli ◽  
Brunella Posteraro ◽  
Massimiliano Papi ◽  
Riccardo Torelli ◽  
Alessandro Maiorana ◽  
...  

ABSTRACTAspergillus fumigatusbiofilms represent a problematic clinical entity, especially because of their recalcitrance to antifungal drugs, which poses a number of therapeutic implications for invasive aspergillosis, the most difficult-to-treatAspergillus-related disease. While the antibiofilm activities of amphotericin B (AMB) deoxycholate and its lipid formulations (e.g., liposomal AMB [LAMB]) are well documented, the effectiveness of these drugs in combination with nonantifungal agents is poorly understood. In the present study,in vitrointeractions between polyene antifungals (AMB and LAMB) and alginate lyase (AlgL), an enzyme degrading the polysaccharides produced as extracellular polymeric substances (EPSs) within the biofilm matrix, againstA. fumigatusbiofilms were evaluated by using the checkerboard microdilution and the time-kill assays. Furthermore, atomic force microscopy (AFM) was used to image and quantify the effects of AlgL-antifungal combinations on biofilm-growing hyphal cells. On the basis of fractional inhibitory concentration index values, synergy was found between both AMB formulations and AlgL, and this finding was also confirmed by the time-kill test. Finally, AFM analysis showed that whenA. fumigatusbiofilms were treated with AlgL or polyene alone, as well as with their combination, both a reduction of hyphal thicknesses and an increase of adhesive forces were observed compared to the findings for untreated controls, probably owing to the different action by the enzyme or the antifungal compounds. Interestingly, marked physical changes were noticed inA. fumigatusbiofilms exposed to the AlgL-antifungal combinations compared with the physical characteristics detected after exposure to the antifungals alone, indicating that AlgL may enhance the antibiofilm activity of both AMB and LAMB, perhaps by disrupting the hypha-embedding EPSs and thus facilitating the drugs to reach biofilm cells. Taken together, our results suggest that a combination of AlgL and a polyene antifungal may prove to be a new therapeutic strategy for invasive aspergillosis, while reinforcing the EPS as a valuable antibiofilm drug target.


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