Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for Aspergillus spp. for the CLSI M38-A2 Broth Microdilution Method

Espinel-Ingroff, Ana; Chowdhary, Anuradha; González, Gloria M.; Lass‐Flörl, Cornelia; Martín-Mazuelos, Estrella; Meis, Jacques F.; Peláez, Teresa; Pfaller, Michael A.; Turnidge, John

doi:10.1128/aac.00636-13

Cited by 85 publications

(63 citation statements)

References 41 publications

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“…Both A. lentulus and N. udagawae exhibited relatively decreased sensitivities to itraconazole (mode MICs, 2 and 1 g/ml, respectively) and voriconazole (mode MIC, 1 g/ml for both) compared to the sensitivities of A. fumigatus (Table 1) (25). In contrast to the MICs of these azoles, the isavuconazole MICs were lower for the A. lentulus and N. udagawae isolates (mode MICs, 0.25 and 0.125 g/ml, respectively), as well as for A. fumigatus, as tested here (Table 1) and by others (26). A. lentulus isolates also demonstrated decreased susceptibilities to amphotericin B (range, 0.5 to 4 g/ml; mode MIC, 2 g/ml; 93.3% of isolates showed MICs of Ն2 g/ml [data not shown separately]), corroborating observations by other investigators (2,27).…”

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confidence: 51%

“…Prior studies evaluating A. lentulus echinocandin susceptibilities also suggest that nontarget characteristics, such as fungal cell wall composition, architecture, and/or hydrophobicity, may impact antifungal susceptibilities (44). The isavuconazole MICs of A. lentulus and N. udagawae isolates in this study, albeit low, varied (Table 1) and were comparable to the modal A. fumigatus MICs recently reported (26). Future studies are necessary to define the clinical significance of these findings.…”

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confidence: 53%

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Isavuconazole Activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, Emerging Fungal Pathogens with Reduced Azole Susceptibility

Datta¹,

Rhee²,

Byrnes³

et al. 2013

J Clin Microbiol

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confidence: 51%

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confidence: 53%

Isavuconazole Activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, Emerging Fungal Pathogens with Reduced Azole Susceptibility

Datta¹,

Rhee²,

Byrnes³

et al. 2013

J Clin Microbiol

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“…Minimum effective concentrations of echinocandins were defined as the lowest drug concentration that allowed the growth of small, rounded, and degenerated hyphae. CLSI has established epidemiologic cutoff values (ECVs) for six Aspergillus species, namely A. fumigatus, A. flavus, A. niger, A. terreus, A. nidulans, and A. versicolor for ITC, VRC, POS, and ISA (16,17). However, breakpoints or ECVs for rare Aspergillus species identified in this study are not available.…”

Section: Methodsmentioning

confidence: 69%

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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“…Isavuconazole has demonstrated potent in vitro antifungal activity against most Aspergillus species, including Aspergillus terreus strains that were resistant to amphotericin B. 10,11 Unfortunately, isavuconazole is not available in China. The in vitro activity of posaconazole against Aspergillus terreus is greater than itraconazole and voriconazole 12 ; therefore, we used posaconazole to treat this patient.…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Lung Aspergillus terreus Infection After a Second Hematopoietic Stem Cell Transplant in a Patient With Myelodysplastic Syndrome

Chen¹,

Qian²,

Yang³

et al. 2019

Exp Clin Transplant

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A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load. The grafts were implanted successfully, but the patient developed an invasive fungal infection. A lung biopsy was performed, and the pathogen was confirmed to be Aspergillus terreus via gene sequencing and analysis. The combined treatment of micafungin and posaconazole had good efficacy in this case, and this patient now receives close follow-up and receives oral posaconazole for antifungal maintenance treatment. Key words: Donor-specific antibodies, Fungal infection, Graft failure Case ReportA 24-year-old man was diagnosed with myelodysplastic syndrome (MDS, RAEB-II) in May 2015. He had an intermediate karyotype (+8) and pancytopenia. The bone marrow showed 14% blast cells, which was categorized as very high risk (6.5 points) according to the Revised International Prognostic Scoring System. 1 The patient needed a transplant; however, no human leukocyte antigen (HLA)-identical sibling or unrelated donor was available. The patient's father, who was HLA halfmatched, agreed to donate stem cells. The treatment approach before transplant consisted of omacetaxine mepesuccinate (2 mg intravenously [IV], once daily from day 1 to day 7), cytarabine (25 mg subcutaneously, twice daily from day 1 to day 7), and aclarubicin (20 mg IV, once daily on days 1, 3, and 5) every 28 days for 1 course and 25 mg/m 2 IV decitabine once daily for 5 days every 28 days for 2 courses.In August 2015, the patient received a haploidentical hematopoietic stem cell transplant (HSCT; peripheral blood + bone marrow) with a myeloablative conditioning regimen based on cytarabine (4 g/m 2 /d IV for 2 days), busulfan (3.2 mg/kg/d IV for 3 days), cyclophosphamide (3.6 g/m 2 /d IV for 2 days), and antilymphocyte globulin (10 mg/kg/d IV for 4 days). Graft-versus-host disease prophylaxis consisted of mycophenolate mofetil, cyclosporine, and short-term methotrexate. The patient received 8.46 × 10 6 CD34-positive cells/kg. On day 21 after transplant, granulocytes and platelets were not engrafted into the patient. The bone marrow puncture report suggested extremely low bone marrow proliferation. Primary engraftment failure was considered, possibly associated with donor-specific antibodies (DSAs).Peripheral blood specimens from both the patient and the parents were sent for DSA detection. The results suggested that there were strongly positive anti-HLA-I antibodies in the patient's body. Analysis of specific sites (detection performed using HLA-I, HLA-II, and major histocompatibility complex class I p...

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Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for Aspergillus spp. for the CLSI M38-A2 Broth Microdilution Method

Cited by 85 publications

References 41 publications

Isavuconazole Activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, Emerging Fungal Pathogens with Reduced Azole Susceptibility

Isavuconazole Activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, Emerging Fungal Pathogens with Reduced Azole Susceptibility

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

Successful Treatment of Lung Aspergillus terreus Infection After a Second Hematopoietic Stem Cell Transplant in a Patient With Myelodysplastic Syndrome

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