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Jacques F Meis - One of the best experts on this subject based on the ideXlab platform.
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emergence of azole resistant invasive aspergillosis in hsct recipients in germany
2015Co-Authors: Joerg Steinmann, Oliver A. Cornely, Axel Hamprecht, Jacques F Meis, Maria J G T Vehreschild, Dieter Buchheidt, Birgit Spiess, Michael Koldehoff, Jan Buer, Peter-michael RathAbstract:OBJECTIVES: Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated. METHODS: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats. RESULTS: In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France. CONCLUSIONS: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.
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multi azole resistant aspergillus fumigatus in the environment in tanzania
2014Co-Authors: Anuradha Chowdhary, Cheshta Sharma, Mara Van Den Boom, Jan Bart Yntema, Ferry Hagen, Paul E Verweij, Jacques F MeisAbstract:OBJECTIVES: Azole resistance in Aspergillus fumigatus isolates has been increasingly reported with variable prevalence worldwide and is challenging the effective management of aspergillosis. Here we report the coexistence of both TR(3)(4)/L98H and TR(4)(6)/Y121F/T289A resistance mechanisms in azole-resistant A. fumigatus (ARAF) isolates originating from Tanzania, Africa. METHODS: A total of 30 soil and woody debris samples from the surroundings of Kilimanjaro Christian Medical Centre, Moshi, Tanzania, were processed for detection of ARAF isolates and were investigated for susceptibility to itraconazole, voriconazole, posaconazole and isavuconazole. All ARAF isolates were subjected to a real-time PCR assay for detection of mutations and were genotyped by microsatellite typing. RESULTS: Of the 30 samples, 29 yielded 108 A. fumigatus isolates. Overall, 15 ARAF isolates were obtained, which included 4 ARAF harbouring the TR(4)(6)/Y121F/T289A mutation and 11 isolates carrying TR(3)(4)/L98H. All four TR(4)(6)/Y121F/T289A A. fumigatus isolates showed high MICs of voriconazole (>16 mg/L) and isavuconazole (8 mg/L). In contrast, the 11 TR(3)(4)/L98H A. fumigatus isolates were pan-azole resistant. The isolates were cross-resistant to azole fungicides. Notably, 20% of environmental samples harboured ARAF and the TR(4)(6)/Y121F/T289A resistance mechanism was found in 5.5% of the soil samples, where it coexisted with TR(3)(4)/L98H. The Tanzanian TR(4)(6)/Y121F/T289A strains had a genotype identical to Dutch clinical TR(4)(6)/Y121F/T289A isolates. CONCLUSIONS: The present study reports the isolation of resistant A. fumigatus strains harbouring the TR(4)(6)/Y121F/T289A mutation from Africa. Recovery of TR(4)(6)/Y121F/T289A from the environment is worrisome and we must strive for effective surveillance of clinical and environmental sources to detect azole resistance in A. fumigatus.
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exploring azole antifungal drug resistance in aspergillus fumigatus with special reference to resistance mechanisms
2014Co-Authors: Anuradha Chowdhary, Cheshta Sharma, Ferry Hagen, Jacques F MeisAbstract:Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However, over a decade, azole resistance in A. fumigatus isolates has been increasingly reported with variable prevalence worldwide and it is challenging the effective management of aspergillosis. The high mortality rates observed in patients with invasive aspergillosis caused by azole-resistant A. fumigatus (ARAF) isolates pose serious challenges to the clinical microbiologist for timely identification of resistance and appropriate therapeutic interventions. The majority of ARAF isolates contain alterations in the cyp51A gene; however, there have been increasing reports on non-cyp51A mutations contributing to azole resistant phenotypes. This review highlights the emergence and various mechanisms implicated in the development of azole resistance in A. fumigatus. We further present recent developments related to the environmental route in the emergence of ARAF isolates and discuss the therapeutic options available.
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emergence of azole resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health
2013Co-Authors: Anuradha Chowdhary, Shallu Kathuria, Jacques F MeisAbstract:Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis and causes one of the highest numbers of deaths among patients with fungal infections [1]. Invasive aspergillosis is the most severe manifestation with an overall annual incidence up to 10% in immunosuppressed patients, whereas chronic pulmonary aspergillosis affects about 3 million, primarily immunocompetent, individuals each year [2]. Three triazole antifungals, namely itraconazole, voriconazole, and posaconazole, are recommended first-line drugs in the treatment and prophylaxis of aspergillosis [3]. However, azole resistance in A. fumigatus isolates is increasingly reported with variable prevalence in Europe, the United States, South America, China, Japan, Iran, and India [4]–[9]. For example, about 10% of strains of A. fumigatus from the Netherlands are itraconazole resistant, and in the United Kingdom, the frequency increased from 0%–5% during 2002–2004 to 17%–20% in 2007–2009 [10]–[13]. In the ARTEMIS global surveillance program involving 62 medical centers, 5.8% of A. fumigatus strains showed elevated MICs to one or more triazoles [5]. Similarly, the prospective SCARE (Surveillance Collaboration on Aspergillus Resistance in Europe) study involving 22 medical centers in 19 countries identified an overall prevalence of 3.4% azole resistance. Azole-resistant A. fumigatus (ARAF) ranged from 0% to 26% among the 22 centres and was detected in 11 (57.9%) of the 19 participating European countries [4 and P.E. Verweij, personal communication]. Interestingly, almost half (48.9%) of the ARAF isolates from the SCARE network in European countries were resistant to multiple azoles and harbored the TR34/L98H mutation in the cyp51A gene [4 and P.E. Verweij, personal communication]. Indeed, multi-azole resistance in A. fumigatus due to the TR34/L98H mutations has become an emerging problem in both Europe and Asia and has been associated with high rates of treatment failures [12]–[14]. Azole antifungal drugs inhibit the ergosterol biosynthesis pathway, specifically the cytochrome p450 sterol 14-α-demethylase encoded by the cyp51A gene, which leads to depletion of ergosterol and accumulation of toxic sterols. The majority of ARAF isolates contain alterations in the target enzyme and the mutated target showed reduced or no binding to the drugs [15]. While most mutations in ARAF isolates were single nucleotide substitutions in the target gene (cyp51A), mutations at other genes such as the cdr1B have also been reported. For example, in the United Kingdom the frequency of ARAF isolates without cyp51A mutations has been reported to be more than 50% [16].
Min Wang - One of the best experts on this subject based on the ideXlab platform.
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an acidic polysaccharide from ziziphus jujuba cv muzao purification and structural characterization
2019Co-Authors: Xiaolong Ji, Qiang Peng, Fan Zhang, Rui Zhang, Min WangAbstract:Abstract A novel acidic polysaccharide fraction (PZMP2-2) was isolated from Ziziphus Jujuba cv. Muzao fruit via hot water extraction and purified by DEAE-Sepharose FF and Sephacryl S-300 column chromatography. PZMP2-2 consisted of rhamnose, arabinose, xylose, galactose, and galacturonic acid in a ratio of 1.18: 5.23: 0.22: 2.68: 2.20, with a molecular weight of 62.73 kDa. Structural features of PZMP2-2 were investigated using FT-IR, SEM, AFM, GC–MS analysis and NMR spectroscopy. Methylation and GC–MS analysis revealed that the main glycosidic bonds in PZMP2-2 comprised 1-linked Galp, 1,3-linked ARAF, 1,2,4-linked Rhap, 1,3-linked Galp, 1,4-linked GalpA and 1,3,5-linked ARAF. NMR analysis indicate that PZMP 2–2 has a linear backbone of (1 → 4)-linked GlcpA and (1 → 2,4)-linked Rhap residues, with branches at the O-4 position, consisting of ARAF and Galp residues.
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purification structural characterization and hypolipidemic effects of a neutral polysaccharide from ziziphus jujuba cv muzao
2018Co-Authors: Xiaolong Ji, Qiang Peng, Min WangAbstract:A neutral polysaccharide (PZMP1) with a molecular weight of 16.97 kDa was isolated from Ziziphus Jujuba cv. Muzao with water extraction, ethanol precipitation, and purification with DEAE-Sepharose Fast Flow and Sephacryl S-300 column chromatography. PZMP1 was structurally characterized with high-performance gel-permeation chromatography, gas chromatography, Fourier transform infrared spectroscopy, methylation analysis, NMR spectroscopy, X-ray diffraction, scanning electron microscopy, and atomic force microscopy. The results show that PZMP1 is a homogeneous heteropolysaccharide composed of arabinose, galactose, glucose, mannose, and xylose in a molar percentage of 17.36: 3.29:2.68:1.05:1.00. The majorly backbone of PZMP1 is composed of 1,3,5-linked ARAF, 1,3-linked ARAF, 1,5-linked ARAF, 1,4-linked Glcp, and 1-linked ARAF, 1-linked Glcp. According to an NMR analysis, the repeating unit of PZMP1 is a linear backbone with branches at positions O-3, and O-5. PZMP1 also displays effective dose-dependent hypolipidemic activity, suggesting that it is a natural hypolipidemic agent, which could contribute to the functional food qualities of jujube fruit.
Qibtiyah Mariyatul - One of the best experts on this subject based on the ideXlab platform.
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PENGARUH PENGAJARAN NAHWU S}ARAF DI ASRAMA MUZAMZAMAH-CHOSYI’AH TERHADAP PRESTASI BELAJAR BIMBINGAN MEMBACA KITAB (BMK) FIQIH DI SEKOLAH MENENGAH PERTAMA NEGERI 3 (SMPN 3) DARUL ULUM JOMBANG
2017Co-Authors: Qibtiyah MariyatulAbstract:Ilmu nahwu s}ARAF merupakan ilmu penghubung antara cara membaca dengan benar pada pembacaan kitab sehingga apabila kita menguasai ilmu nahwu s}ARAF maka kita akan bisa membaca dengan benar dan bisa mengerti maknanya. Adapun tujuan peneliti untuk mengetahui sejauh mana pengaruh pengajaran nahwu s}ARAF terhadap Bimbingan Membaca Kitab (BMK) Fiqih. Pendekatan yang digunakan adalah pendekatan kuantitatif yang mencari hubungan antara variabel X dengan variabel Y. Adapun hasilnya yang diperoleh dari rumus uji t yaitu hasil 20.393, maka nilai t tabel dengan tARAF signifikan 5% dengan N = 30 diperoleh 2,045, karena nilai t hitung lebih besar dari t tabel (20.393 > 2,045), maka hipotesis nol (H0) ditolah dan hipotesis alternative (Ha) diterima. Kesimpulannya adalah terdapat pengaruh pengajaran nahwu s}ARAF terhadap prestasi belajar Bimbingan Membaca Kitab (BMK) Fiqih
Mariyatul Qibtiyah - One of the best experts on this subject based on the ideXlab platform.
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pengaruh pengajaran nahwu s ARAF di asrama muzamzamah chosyi ah terhadap prestasi belajar bimbingan membaca kitab bmk fiqih di sekolah menengah pertama negeri 3 smpn 3 darul ulum jombang
2017Co-Authors: Mariyatul QibtiyahAbstract:Ilmu nahwu s}ARAF merupakan ilmu penghubung antara cara membaca dengan benar pada pembacaan kitab sehingga apabila kita menguasai ilmu nahwu s}ARAF maka kita akan bisa membaca dengan benar dan bisa mengerti maknanya. Adapun tujuan peneliti untuk mengetahui sejauh mana pengaruh pengajaran nahwu s}ARAF terhadap Bimbingan Membaca Kitab (BMK) Fiqih. Pendekatan yang digunakan adalah pendekatan kuantitatif yang mencari hubungan antara variabel X dengan variabel Y. Adapun hasilnya yang diperoleh dari rumus uji t yaitu hasil 20.393, maka nilai t tabel dengan tARAF signifikan 5% dengan N = 30 diperoleh 2,045, karena nilai t hitung lebih besar dari t tabel (20.393 > 2,045), maka hipotesis nol (H0) ditolah dan hipotesis alternative (Ha) diterima. Kesimpulannya adalah terdapat pengaruh pengajaran nahwu s}ARAF terhadap prestasi belajar Bimbingan Membaca Kitab (BMK) Fiqih.
Xiaolong Ji - One of the best experts on this subject based on the ideXlab platform.
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an acidic polysaccharide from ziziphus jujuba cv muzao purification and structural characterization
2019Co-Authors: Xiaolong Ji, Qiang Peng, Fan Zhang, Rui Zhang, Min WangAbstract:Abstract A novel acidic polysaccharide fraction (PZMP2-2) was isolated from Ziziphus Jujuba cv. Muzao fruit via hot water extraction and purified by DEAE-Sepharose FF and Sephacryl S-300 column chromatography. PZMP2-2 consisted of rhamnose, arabinose, xylose, galactose, and galacturonic acid in a ratio of 1.18: 5.23: 0.22: 2.68: 2.20, with a molecular weight of 62.73 kDa. Structural features of PZMP2-2 were investigated using FT-IR, SEM, AFM, GC–MS analysis and NMR spectroscopy. Methylation and GC–MS analysis revealed that the main glycosidic bonds in PZMP2-2 comprised 1-linked Galp, 1,3-linked ARAF, 1,2,4-linked Rhap, 1,3-linked Galp, 1,4-linked GalpA and 1,3,5-linked ARAF. NMR analysis indicate that PZMP 2–2 has a linear backbone of (1 → 4)-linked GlcpA and (1 → 2,4)-linked Rhap residues, with branches at the O-4 position, consisting of ARAF and Galp residues.
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purification structural characterization and hypolipidemic effects of a neutral polysaccharide from ziziphus jujuba cv muzao
2018Co-Authors: Xiaolong Ji, Qiang Peng, Min WangAbstract:A neutral polysaccharide (PZMP1) with a molecular weight of 16.97 kDa was isolated from Ziziphus Jujuba cv. Muzao with water extraction, ethanol precipitation, and purification with DEAE-Sepharose Fast Flow and Sephacryl S-300 column chromatography. PZMP1 was structurally characterized with high-performance gel-permeation chromatography, gas chromatography, Fourier transform infrared spectroscopy, methylation analysis, NMR spectroscopy, X-ray diffraction, scanning electron microscopy, and atomic force microscopy. The results show that PZMP1 is a homogeneous heteropolysaccharide composed of arabinose, galactose, glucose, mannose, and xylose in a molar percentage of 17.36: 3.29:2.68:1.05:1.00. The majorly backbone of PZMP1 is composed of 1,3,5-linked ARAF, 1,3-linked ARAF, 1,5-linked ARAF, 1,4-linked Glcp, and 1-linked ARAF, 1-linked Glcp. According to an NMR analysis, the repeating unit of PZMP1 is a linear backbone with branches at positions O-3, and O-5. PZMP1 also displays effective dose-dependent hypolipidemic activity, suggesting that it is a natural hypolipidemic agent, which could contribute to the functional food qualities of jujube fruit.