Distribution of Aspergillus Species and Prevalence of Azole Resistance in Respiratory Samples From Swiss Tertiary Care Hospitals
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SUBMITTER: Ragozzino S
PROVIDER: S-EPMC8802793 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among Aspergillus fumigatus isolates. Clinical and demographic data were also analyzed. A total of 3,336 respiratory samples from 287 CF patients were collected during two 6-month periods in 2007 and 2009. Azole resistance was detected using an itraconazole screening agar (4 mg/liter) and the EUCAST method. cyp51A gene sequencing and microsatellite genotyping were performed for isolates from patients harboring azole-resistant A. fumigatus. Aspergillus spp. were present in 145 patients (51%), of whom 63 (22%) were persistently colonized. Twelve patients (4%) harbored other molds. Persistently colonized patients were older, provided more samples, and more often had a chronic bacterial infection. Six of 133 patients (4.5%) harbored azole-nonsusceptible or -resistant A. fumigatus isolates, and five of those six patients had isolates with Cyp51A alterations (M220K, tandem repeat [TR]/L98H, TR/L98H-S297T-F495I, M220I-V101F, and Y431C). All six patients were previously exposed to azoles. Genotyping revealed (i) microevolution for A. fumigatus isolates received consecutively over the 2-year period, (ii) susceptible and resistant isolates (not involving TR/L98H isolates) with identical or very closely related genotypes (two patients), and (iii) two related susceptible isolates and a third unrelated resistant isolate with a unique genotype and the TR/L98H resistance combination (one patient). Aspergilli were frequently found in Danish CF patients, with 4.5% of the A. fumigatus isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.
| S-EPMC3122734 | biostudies-literature
Project description:ObjectivesAzole resistance among Aspergillus fumigatus isolates is a growing concern worldwide. Induction of mutations during azole therapy, environment-acquired mutations caused by azole fungicides and intrinsic resistance of cryptic Fumigati species all contribute to the burden of resistance. However, there is a lack of data in Canada on this emerging threat.MethodsTo gain insights into the magnitude and mechanisms of resistance, a 14?year collection of Aspergillus section Fumigati comprising 999 isolates from 807 patients at a Montreal hospital was screened for azole resistance, and resistance mechanisms were investigated with the combined use of genome sequencing, 3D modelling and phenotypic efflux pump assays.ResultsOverall azole resistance was low (4/807 patients; 0.5%). A single azole-resistant A. fumigatus sensu stricto strain, isolated from a patient with pulmonary aspergillosis, displayed efflux-pump-mediated resistance. Three patients were colonized or infected with azole-resistant cryptic Fumigati species (one Aspergillus thermomutatus, one Aspergillus lentulus and one Aspergillus turcosus). Evidence is presented that azole resistance is efflux-pump-mediated in the A. turcosus isolate, but not in the A. lentulus and A. thermomutatus isolates.ConclusionsAzole resistance is rare in our geographic area and currently driven by cryptic Fumigati species. Continued surveillance of emergence of resistance is warranted.
| S-EPMC7069474 | biostudies-literature
Project description:Although classical human astroviruses (HAstV) are known to be a leading cause of viral gastroenteritis, the pathogenesis and clinical manifestations of novel HAstV remain largely unknown. There is mounting evidence that, in contrast to classical astroviruses, novel HAstV exhibit tropism for the upper respiratory tract. This one-year period prevalence screened all available clinical nasopharyngeal swab samples collected from pediatric patients aged ≤5 years for novel and classical HAstV using real-time reverse transcription polymerase chain reaction. A total of 205 samples were tested; two novel HAstV cases were detected for a prevalence of 1.3%, with viral loads suggesting active upper respiratory tract replication. No classical HAstV was detected.
| S-EPMC6175467 | biostudies-literature
Project description:Respiratory specimens obtained from patients with chronic forms of aspergillosis contain phenotypic variants of azole-resistant Aspergillus fumigatus (ARAF) that co-exist in the airway. Here we aimed to study whether phenotypic variants of ARAF that co-exist in clinical specimens were genetically distinct. A panel of six phenotypic variants of ARAF cultured from two sputum samples collected from two patients with chronic aspergillosis were included. Preliminary identification of all isolates was obtained using MALDI-ToF mass spectrometry and confirmed by AsperGenius® real-time PCR assay. Antifungal susceptibility testing was determined using EUCAST E.Def 9.3 microbroth dilution. Genomic DNA libraries were constructed with the Illumina TruSeq Nano kit. Prepared whole-genome libraries were sequenced on an Illumina HiSeq 2500. Whole genome data were converted into presence/absence of a SNP with respect to the Af293 reference genome. Colonies of ARAF that co-existed in one respiratory sample demonstrated marked phenotypic diversity. Two cyp51A polymorphisms were found among azole-resistant isolates: TR34/L98H/T289A/I364V/G448S was consistently present in four variants with a pan-azole resistant phenotype and TR34/L98H was detected in two variants (itraconazole MIC > 16 mg/L). WGS typing showed that despite marked phenotypic variation, each sample contained a population of highly genetically related azole-resistant A. fumigatus variants. Our SNP analysis suggest that mechanisms additional to genetic-based variation are responsible for phenotypic diversity. Our data demonstrate that the phenotypic variants of ARAF that co-exist in clinical specimens are highly clonal and strongly suggest their origination from a single common ancestor.
| S-EPMC9469045 | biostudies-literature
Project description:Aspergillus section Nigri includes species of interest for animal and human health, although studies on species distribution are limited to human cases. Data on the antifungal susceptibilities and the molecular mechanism of triazole resistance in strains belonging to this section are scant. Forty-two black Aspergillus strains from human patients (16 isolates), animals (14 isolates), and the environment (12 isolates) were molecularly characterized and their in vitro triazole susceptibilities investigated. Aspergillus tubingensis was isolated from humans, animals, and environmental settings, whereas Aspergillus awamori and Aspergillus niger were isolated exclusively from humans. Phylogenetic analyses of ?-tubulin and calmodulin gene sequences were concordant in differentiating A. tubingensis from A. awamori and A. niger Voriconazole and posaconazole (PSZ) were the most active triazoles. One A. tubingensis strain was resistant to itraconazole and PSZ and one A. niger strain to PSZ. Sequence analysis of the cyp51A gene revealed different sequence types within a species, and A. tubingensis strains were also phylogenetically distinct from A. awamori/A. niger strains according to the strain origin and susceptibility profile. Genetic analysis of the cyp51A sequences suggests that two nonsynonymous mutations resulting in amino acid substitutions in the CYP51A protein (changes of L to R at position 21 [L21R] and of Q to R at position 228 [Q228R]) might be involved in azole resistance. Though azole resistance in black Aspergillus isolates from animals and rural environments does not represent a threat to public health in Southern Italy, the use of triazoles in the clinical setting needs to better monitored. The cyp51A sequence is useful for the molecular identification of black Aspergillus, and point mutations in protein sequences could be responsible for azole resistance phenomena.
| S-EPMC5005483 | biostudies-literature
Project description:PurposeTo investigate species diversity and prevalence of antifungal resistance among clinical isolates of Aspergillus spp. in Shanghai, China.Patients and methodsIn this study, the Aspergillus spp. isolates were analyzed by multilocus sequence typing (MLST) targeting the internal transcribed spacer (ITS) regions, and partial ?-tubulin (BenA) and calmodulin (CaM) genes. The susceptibilities of these isolates to nine antifungal agents were determined according to the protocol in document M38-A3 established by the Clinical and Laboratory Standards Institute (CLSI).ResultsThe most common Aspergillus spp. was A. fumigatus (58.2%), followed by the A. flavus complex (23.5%), and A. niger complex (15.3%). Isolates belonging to A. tamarii and A. effusus of the A. flavus complex and A. tubingensis and A. awamori of the A. niger complex were identified. Moreover, several mutations were found in the azole target cyp51A gene (TR46/Y121F/T289A and F46Y, G89G, M172V, N248T and D255E) in azole-resistant isolates of A. fumigatus.ConclusionThe results of our study revealed a diversity of species in the lower respiratory tract of inpatients in Shanghai and approximately 9% of our isolates were resistant to at least one of the triazole antifungals. Formulation of local treatment strategies to combat emerging azole resistance and species diversity in clinically relevant Aspergillus spp. is needed.
| S-EPMC7778383 | biostudies-literature
Project description:Aspergillus niger is a common clinical isolate. Multiple species comprise the Aspergillus section Nigri and are separable using sequence data. The antifungal susceptibility of these cryptic species is not known. We determined the azole MICs of 50 black aspergilli, 45 from clinical specimens, using modified EUCAST (mEUCAST) and Etest methods. Phylogenetic trees were prepared using the internal transcribed spacer, beta-tubulin, and calmodulin sequences to identify strains to species level and the results were compared with those obtained with cyp51A sequences. We attempted to correlate cyp51A mutations with azole resistance. Etest MICs were significantly different from mEUCAST MICs (P < 0.001), with geometric means of 0.77 and 2.79 mg/liter, respectively. Twenty-six of 50 (52%) isolates were itraconazole resistant by mEUCAST (MICs > 8 mg/liter), with limited cross-resistance to other azoles. Using combined beta-tubulin/calmodulin sequences, the 45 clinical isolates grouped into 5 clades, A. awamori (55.6%), A. tubingensis (17.8%), A. niger (13.3%), A. acidus (6.7%), and an unknown group (6.7%), none of which were morphologically distinguishable. Itraconazole resistance was found in 36% of the isolates in the A. awamori group, 90% of the A. tubingensis group, 33% of the A. niger group, 100% of the A. acidus group, and 67% of the unknown group. These data suggest that cyp51A mutations in section Nigri may not play as important a role in azole resistance as in A. fumigatus, although some mutations (G427S, K97T) warrant further study. Numerous cryptic species are found in clinical isolates of the Aspergillus section Nigri and are best reported as "A. niger complex" by clinical laboratories. Itraconazole resistance was common in this data set, but azole cross-resistance was unusual. The mechanism of resistance remains obscure.
| S-EPMC3186969 | biostudies-literature
Project description:BackgroundAspergillus species cause a variety of serious clinical conditions with increasing trend in antifungal resistance. The present study aimed at evaluating hospital epidemiology and antifungal susceptibility of all isolates recorded in our clinical database since its implementation.MethodsData on date of isolation, biological samples, patients' age and sex, clinical settings, and antifungal susceptibility tests for all Aspergillus spp. isolated from 2015 to 2022 were extracted from the clinical database. Score test for trend of odds, non-parametric Mann Kendall trend test and logistic regression analysis were used to analyze prevalence, incidence, and seasonality of Aspergillus spp. isolates.ResultsA total of 1126 Aspergillus spp. isolates were evaluated. A. fumigatus was the most prevalent (44.1%) followed by A. niger (22.3%), A. flavus (17.7%) and A. terreus (10.6%). A. niger prevalence increased over time in intensive care units (p-trend = 0.0051). Overall, 16 (1.5%) were not susceptible to one azole compound, and 108 (10.9%) to amphotericin B, with A. niger showing the highest percentage (21.9%). The risk of detecting A. fumigatus was higher in June, (OR = 2.14, 95% CI [1.16; 3.98] p = 0.016) and reduced during September (OR = 0.48, 95% CI [0.27; 0.87] p = 0.015) and October as compared to January (OR = 0.39, 95% CI [0.21; 0.70] p = 0.002. A. niger showed a reduced risk of isolation from all clinical samples in the month of June as compared to January (OR = 0.34, 95% CI [0.14; 0.79] p = 0.012). Seasonal trend for A. flavus showed a higher risk of detection in September (OR = 2.7, 95% CI [1.18; 6.18] p = 0.019), October (OR = 2.32, 95% CI [1.01; 5.35] p = 0.048) and November (OR = 2.42, 95% CI [1.01; 5.79] p = 0.047) as compared to January.ConclusionsThis is the first study to analyze, at once, data regarding prevalence, time trends, seasonality, species distribution and antifungal susceptibility profiles of all Aspergillus spp. isolates over a 8-year period in a tertiary care center. Surprisingly no increase in azole resistance was observed over time.
| S-EPMC10988875 | biostudies-literature
Project description:We present the draft genome sequences of two clinical strains of Aspergillus turcosus, one azole-susceptible (strain HMR-AF-23/LSPQ-01275) and the other azole-resistant (strain HMR-AF-1038/LSPQ-01280), isolated from bronchoalveolar lavage fluid of two adult patients. These two strains are the first reported clinical isolates of A. turcosus.
| S-EPMC6318367 | biostudies-literature
Project description:BackgroundAcute respiratory infection (ARI) is responsible for about 30-50 percent of visits to health facilities and for about 20-30 percent of admissions to hospitals in Nepal for children under 5 years old. Incidence of ARI in children among under-five years of age is 344 per 1000 in Nepal. Hence, the study aims to find out the prevalence and factors associated with acute respiratory infection among under-five children.MethodsA cross-sectional study was conducted at Nepal Medical College and Teaching Hospital and International Friendship Children's Hospital (IFCH) in Kathmandu among children of age 2-59 months attending Pediatric OPD. A total of 286 children were selected using the non-probability (convenient) sampling technique. Data were collected using pre-tested semi-structured tool through interview schedule, and descriptive and inferential statistical analyses were used.ResultsOut of 286 children, more than half of children (60.8%) had Acute Respiratory Infection (ARI). Nearly one-fifth of the children had severe or very severe pneumonia. Acute respiratory infection was significantly associated with religion followed by the family (p = 0.009, OR = 4.59 CI = 1.47-14.36), presence of the child in the kitchen while cooking (p = 0.001, OR = 2.03 CI = 1.17-3.51), and presence of respiratory tract infection in family (p = <0.001 OR = 2.83 CI = 1.59-5.05).ConclusionThe study concluded that male children are more susceptible to acute respiratory infection than female children. Parents and family members should be aware of the prevention of acute respiratory infection by addressing and minimizing the factors contributing to ARI.
| S-EPMC8989212 | biostudies-literature