<i>In Vitro</i>
            Echinocandin Susceptibility of
            <i>Aspergillus</i>
            Isolates from Patients Enrolled in the Transplant-Associated Infection Surveillance Network

Lockhart, Shawn R.; Zimbeck, Alicia J.; Baddley, John W.; Marr, Kieren A.; Andes, David R.; Walsh, Thomas J.; Kauffman, Carol A.; Kontoyiannis, Dimitrios P.; Ito, James I.; Pappas, Peter G.; Chiller, Tom

doi:10.1128/aac.00428-11

Cited by 36 publications

(20 citation statements)

References 17 publications

(15 reference statements)

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“…Similar rates of high antifungal resistance were reported in the Spanish FILPOP study that showed 40% of cryptic Aspergillus species be- ing resistant to one antifungal agent in vitro (9). Antifungal susceptibility data in the present study and from previous reports showed species-independent results, with strains of the same species exhibiting various susceptibility patterns (8,9,33). Finally, life-threatening invasive aspergillosis due to rare and cryptic Aspergillus species is complicated by limited therapeutic options.…”

Section: Discussionsupporting

confidence: 75%

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: Discussionsupporting

confidence: 75%

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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“…In another study, the mean MIC 90 values for anidulafungin, micafungin, and caspofungin were 0.002 mg/liter, 0.002 mg/liter, and 0.032 mg/liter, respectively (36). Lockhart et al also determined the echinocandin MEC values against 28 A. flavus isolated from patients with transplant-associated infections (37). The MEC ranges for all isolates were as follows: caspofungin and micafungin, 0.008 to 0.03 mg/liter; and anidulafungin, 0.008 to 0.015 mg/liter.…”

Section: Discussionmentioning

confidence: 99%

Genetic Diversity and In Vitro Antifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates

Armaki

Hedayati

Ansari

et al. 2017

Antimicrob Agents Chemother

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Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and subtropical countries. Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial ␤-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. In addition, genotyping was performed using a short-tandem-repeat (STR) assay of a panel of six microsatellite markers (A. flavus 2A, 2B, 2C, 3A, 3B, and 3C), in order to determine the genetic variation and the potential relationship between clinical and environmental isolates. The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all isolates were (in increasing order): posaconazole, 0.13 mg/liter; anidulafungin, 0.16 mg/liter; itraconazole, 0.29 mg/liter; caspofungin, 0.42 mg/liter; voriconazole, 0.64 mg/liter; isavuconazole, 1.10 mg/liter; amphotericin B, 3.35 mg/liter; and flucytosine, 62.97 mg/liter. All of the clinical isolates were genetically different. However, an identical microsatellite genotype was found between a clinical isolate and two environmental strains. In conclusion, posaconazole and anidulafungin showed the greatest in vitro activity among systemic azoles and echinocandins, respectively. However, the majority of the A. flavus isolates showed reduced susceptibility to amphotericin B. Antifungal susceptibility of A. flavus was not linked with the clinical or environmental source of isolation. Microsatellite genotyping may suggest an association between clinical and environmental strains, although this requires further investigation.

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“…In vitro reduced susceptibility of Aspergillus fumigatus isolates to echinocandins can be developed via FKS-dependent and FKS-independent mechanisms (2). Although clinical resistance of Aspergillus to echinocandins is limited (3), breakthrough infections in patients treated with echinocandins has been reported (4), and non-wild-type clinical isolates with minimal effective concentrations (MECs) above the epidemiological cutoff value have been found (5). Sensititre YeastOne (YO) is an adapted susceptibility system of the microbroth CLSI method based on the M27-A3 standard for yeasts, which uses alamarBlue as a colorimetric indicator.…”

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confidence: 99%

Comparative Evaluation of Sensititre YeastOne and CLSI M38-A2 Reference Method for Antifungal Susceptibility Testing of Aspergillus spp. against Echinocandins

2017

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Sensititre YeastOne (YO) panels were assessed for in vitro susceptibility testing of echinocandins against 39 isolates of Aspergillus fumigatus, A. flavus, and A. terreus, including two echinocandin-resistant A. fumigatus strains, using different inocula (10 3 , 10 4 , and 10 5 CFU/ml), incubation times (16 to 48 h), and endpoints (first blue or purple well) and compared to CLSI M38-A2. The best agreement was found with an inoculum of 10 4 CFU/ml, incubation times of 20 h for A. flavus and of 30 h for A. fumigatus and A. terreus, and reading the first purple well. The reproducibility within Ϯ1 2-fold dilutions was 100% for all three echinocandins. YO color endpoints were 2 to 3 2-fold dilutions lower than CLSI minimum effective concentrations (MECs) of caspofungin and 1 to 2 2-fold dilutions higher than CLSI MECs of micafungin. For anidulafungin, off-scale YO color endpoints were observed. Nevertheless, A. fumigatus echinocandin-resistant isolates were detected after 24 h of incubation.KEYWORDS echinocandins, Aspergillus spp., Sensititre, antifungal susceptibility testing, MEC A spergillus isolates with reduced susceptibility to current antifungal agents have been increasingly reported, highlighting the importance of antifungal susceptibility testing in clinical microbiology laboratory routine (1). In vitro reduced susceptibility of Aspergillus fumigatus isolates to echinocandins can be developed via FKS-dependent and FKS-independent mechanisms (2). Although clinical resistance of Aspergillus to echinocandins is limited (3), breakthrough infections in patients treated with echinocandins has been reported (4), and non-wild-type clinical isolates with minimal effective concentrations (MECs) above the epidemiological cutoff value have been found (5). Sensititre YeastOne (YO) is an adapted susceptibility system of the microbroth CLSI method based on the M27-A3 standard for yeasts, which uses alamarBlue as a colorimetric indicator. Sensititre YeastOne has been extensively evaluated for yeasts. There are fewer studies for molds, demonstrating high levels of agreement with the reference methodology for amphotericin B and azoles with Aspergillus spp. (6-12), while limited data exist for echinocandins. Since Sensititre YeastOne is widely used in routine microbiology laboratories, the aim of the present study was to assess its performance for in vitro susceptibility testing of echinocandins against the three most commonly isolated Aspergillus spp. -A. fumigatus, A. flavus, and A. terreus-compared

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In Vitro Echinocandin Susceptibility of Aspergillus Isolates from Patients Enrolled in the Transplant-Associated Infection Surveillance Network

Cited by 36 publications

References 17 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

Genetic Diversity and In Vitro Antifungal Susceptibility of 200 Clinical and Environmental Aspergillus flavus Isolates

Comparative Evaluation of Sensititre YeastOne and CLSI M38-A2 Reference Method for Antifungal Susceptibility Testing of Aspergillus spp. against Echinocandins

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