Isavuconazole
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Treatment failure: 2 case reports In a case series, a 52-year-old man and a 61 years old man exhibited treatment failure during treatment with isavuconazole for invasive aspergillosis. Case 1: A 52-year-old man was diagnosed with acute myeloid leukaemia (AML) in 2017. Four months after the diagnosis, he underwent haplo-identical stem cell transplantation (SCT) (day 0). However, he had incomplete haematologic reconstitution and developed graft-versus host disease of the digestive tract, which was treated with ruxolitinib and unspecified corticosteroids. For invasive fungal diseases (IFD) prophylaxis, he was administered posaconazole. On day 65, he was diagnosed with probable invasive aspergillosis. His serum samples were found to be positive for A. fumigatus. His treatment was then changed to oral isavuconazole 200 mg/day on the same day. On day 126, his chest CT revealed persistence of the pulmonary lesions. This exhibited isavuconazole treatment failure. Therefore, his treatment was switched to amphotericin B liposomal. Thereafter, his serum samples became repeatedly positive for A. fumigatus and galactomannan antigen DNA. On day 158, a TR34-L98H azole–resistant A. fumigatus fungus was noted in his bronchial aspirate. He died 182 days following the SCT. Case 2: A 61-year-old man was diagnosed with AML in 2013. Four months after the diagnosis, he underwent first allogenic haematopoietic SCT. Three years after his first transplantation, he experienced a relapse, and underwent a second allogenic haematopoietic SCT (day 0), which was followed by severe sepsis with Escherichia coli. The chest CT performed on day 4 showed an excavated nodule, and the A. fumigatus biomarker was found to be repeatedly positive, indicating probable invasive aspergillosis. On day 5, he was initiated on oral isavuconazole 200 mg/day. But, on day 12, he developed graft-versus host disease, for which he received prednisolone, ruxolitinib and tacrolimus. On day 92, he developed fever, asthenia and thoracic pain, and his chest CT revealed multiple micronodules. On days 95–116, systematic fungal surveillance testing of serum samples revealed 3 tests positive for Rhizomucor DNA, 1 test positive for galactomannan antigen, 4 tests positive for A. fumigatus DNA. Two cultures of pulmonary samples performed on days 114 and 116 were found to be positive for A. fumigatus. This exhibited isavuconazole treatment failure. Therefore, he was switched to amphotericin B liposomal on day 117. However, on day 129, he died. Author comment: "We present 2 fatal cases of invasive fungal disease with isavuconazole treatment failure in immunocompromised patients". Bellanger A-P, et al. Invasive fungal disease, isavuconazole treatment failure, and death in acute myeloid leukemia patients. Emerging Infectious Diseases 25: 1778-1779, No. 9, Sep 2019. Available from: URL: http://doi.org/10.3201/ 803443000 eid2509.190598 - France
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Reactions 4 Jan 2020 No. 1785
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