<i>Aspergillus lentulus:</i> An Under-recognized Cause of Antifungal Drug-Resistant Aspergillosis

Nematollahi, Saman; Permpalung, Nitipong; Zhang, Sean X.; Morales, Megan; Marr, Kieren A.

doi:10.1093/ofid/ofab392

Cited by 19 publications

(14 citation statements)

References 37 publications

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“…MIC test strip overestimation was previously described by other authors. 22 These phenotypes could be correlated to cryptic species as A. lentulus , morphologically indistinguishable from A. fumigatus sensu stricto , or other cryptic species in flavi and nigri sections, revealing the emerging importance of molecular species identification, as reported by Nargesi et al 23 , 24 …”

Section: Discussionmentioning

confidence: 72%

Multicenter Italian Study on “In Vitro Activities” of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin for Aspergillus Species: Comparison between SensititreTM YeastOneTM and MIC Test Strip

Cascio¹,

Bazaj²,

Trovato³

et al. 2022

IDR

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In this study the activity of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin against 224 clinical isolates of Aspergillus spp. originating from seven Italian hospitals, was comparatively evaluated with two commercial antifungal susceptibility tests (AST): Sensititre TM YeastOne TM (SYO) and MIC Test Strip. More attention was focused on Isavuconazole activity, given the new introduction of the drug in widely distributed antifungal susceptibilities methods in the clinical microbiology lab. The minimum inhibitory concentrations of antifungal drug that can inhibit the growth of pathogen by 90% (MIC90) for Isavuconazole detected by SYO were 0.5, 1, 0.25, and 2 µg/mL for Aspergillus fumigatus , Aspergillus flavus , Aspergillus terreus , and Aspergillus niger , respectively, whilst they were 0.25, 0.25, 0.5, and 0.75 µg/mL by MIC Test Strip. Essential agreement between the two tested methods for Isavuconazole is 70% for all the species tested, 75.7% for A. fumigatus , 45.2% for A. flavus , 90.6% for A . terreus , and 40% for A. niger . Although the tested strains do not express any phenotypic resistance, MIC results were quite different if tested with microdilution broth or gradient agar method. This is the first Italian multicenter report on Isavuconazole MIC obtained employing the widely used Sensititre TM Yeast One TM (SYO) and MIC Test Strip on clinical isolates of Aspergillus .

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Section: Discussionmentioning

confidence: 72%

Multicenter Italian Study on “In Vitro Activities” of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin for Aspergillus Species: Comparison between SensititreTM YeastOneTM and MIC Test Strip

Cascio¹,

Bazaj²,

Trovato³

et al. 2022

IDR

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“…The three samples tested positive for Aspergillus lentulus , Aspergillus fumigatus , and Aspergillus lentulus , respectively. Identification of A. lentulus was clinically significant given its decreased susceptibility to all three antifungal classes and potentially high rate of mortality (>60%) [ 20 ]. Higher MICs have been observed for voriconazole/itraconazole with A. lentulus [ 21 ], so the decision was made to switch the patient to concurrent high-dose posaconazole and caspofungin IV therapy (300 mg IV BID, 50 mg IV q24h, respectively).…”

Section: Resultsmentioning

confidence: 99%

Fungal Whole-Genome Sequencing for Species Identification: From Test Development to Clinical Utilization

Salem-Bango

Price

Chan

et al. 2023

JoF

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Using next-generation sequencing (NGS), we developed and validated a whole-genome sequencing (WGS)-based clinical test for fungal species identification on clinical isolates. The identification is mainly based on the fungal ribosomal internal transcribed spacer (ITS) region as the primary marker, and additional marker and genomic analysis applied for species within the Mucorales family (using the 28S rRNA gene) and Aspergillus genus (using the beta-tubulin gene and k-mer tree-based phylogenetic clustering). The validation study involving 74 unique fungal isolates (22 yeasts, 51 molds, and 1 mushroom-forming fungus) showed high accuracy, with 100% (74/74) concordance on the genus-level identifications and 89.2% (66/74) concordance on the species level. The 8 discrepant results were due to either the limitation of conventional morphology-based methodology or taxonomic changes. After one year of implementation in our clinical laboratory, this fungal NGS test was utilized in 29 cases; the majority of them were transplant and cancer patients. We demonstrated the utility of this test by detailing five case studies, in which accurate fungal species identification led to correct diagnosis, treatment adjustment or was ruled out for hospital acquired infection. This study provides a model for validation and implementation of WGS for fungal identification in a complex health system that serves a large immunocompromised patient population.

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“…As a sibling species of A. fumigatus , A. lentulus was first described in 2004, which caused fatal infections in four hematopoietic stem cell transplant patients [ 14 , 15 ]. This species is usually difficult to distinguish from A. fumigatus based on phenotypic typing, and can be misidentified as A. fumigatus [ 16 ]. A. lentulus is genetically distinct from A. fumigatus and highly drug resistant.…”

Section: Discussionmentioning

confidence: 99%

Life-threatening pulmonary coinfection with Mycobacterium tuberculosis and Aspergillus lentulus in a diabetic patient diagnosed by metagenome next-generation sequencing

Zhang¹,

Zhu²,

Tu³

et al. 2023

BMC Infect Dis

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Background China has a double burden of diabetes mellitus and tuberculosis. Diabetes mellitus and tuberculosis are both important risk factors for Aspergillus infection. Aspergillus lentulus is an emerging fungal pathogen in China and invasive aspergillosis due to A. lentulus is associated with high mortality. Case presentation A 79-year-old man was admitted to our hospital, complaining of a 7-day history of fever. Five days before admission, he was diagnosed with pulmonary infection at a local hospital, but his symptoms did not relieve after antibiotic therapy. The patient was diagnosed with diabetes mellitus two months ago. About 20 days ago, he began to present chest tightness and shortness of breath after physical activity. After admission, he developed continuous fever and rapid respiratory deterioration, and finally died after his family abandoned treatment. Pulmonary coinfection with M. tuberculosis and A. lentulus was identified by metagenome next-generation sequencing (mNGS) from bronchoalveolar lavage fluid. Conclusions Clinicians and laboratories should be alert to the emerging A. lentulus infection in China due to its drug-resistance and high mortality. In comparison with conventional methods, mNGS has a great advantage for the diagnosis of mixed pulmonary infection.

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Aspergillus lentulus: An Under-recognized Cause of Antifungal Drug-Resistant Aspergillosis

Cited by 19 publications

References 37 publications

Multicenter Italian Study on “In Vitro Activities” of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin for Aspergillus Species: Comparison between SensititreTM YeastOneTM and MIC Test Strip

Multicenter Italian Study on “In Vitro Activities” of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin for Aspergillus Species: Comparison between SensititreTM YeastOneTM and MIC Test Strip

Fungal Whole-Genome Sequencing for Species Identification: From Test Development to Clinical Utilization

Life-threatening pulmonary coinfection with Mycobacterium tuberculosis and Aspergillus lentulus in a diabetic patient diagnosed by metagenome next-generation sequencing

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