S10.5d Disseminated pulmonary infection due to Mortierella wolfii in a 6-year-old patient with X-linked CGD receiving MUD-HSCT

Abstract

S10.5 Fungal respiratory infections in Cystic Fibrosis, September 24, 2022, 10:30 AM - 12:00 PM ObjectivesInvasive fungal infections represent one of the major limiting factors for the successful outcome of patients receiving hematopoietic stem cell transplantation (HSCT). The identification and successful treatment of pretransplant fungal colonization/infections may allow for risk modifications before or at the time of HSCT. Here, we report a case of disseminated pulmonary infection due to a hyaline non-septate mold, Mortierella wolfii in an X-linked chronic granulomatous disease (X-linked CGD) patient that was successfully treated with a combination of terbinafine and posaconazole antifungal therapy.MethodsA 6-year-old male with X-linked CGD from Sri Lanka was admitted to NIH Clinical Center, Bethesda, MD, USA to receive a matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). During pre-transplant immunosuppressive conditioning, the patient developed complicated pulmonary signs resulting in diffuse lymphadenitis and meningitis. Upon further radiologic evaluation, a lung biopsy was performed. The lung biopsy sample was submitted to Microbiology Service of Department of Microbiology at NIH Clinical Center for Fungal culture. Antifungal susceptibility testing was conducted in accordance with the Clinical and Laboratory Standards Institute CLSI M38-A3 guidelines.ResultsA pure heavy growth of white mold grew within 2 days on Sabouraud's Dextrose Agar. Microscopic examination showed hyaline (non-pigmented), non-septate branched hyphae. Sporangiophore-like structures were also present. The species-level identification of the isolate was confirmed as M. wolfii by PCR-sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA.Minimum inhibitory/effective concentrations (μg/ml) were as follows in increasing order: terbinafine = 0.25, amphotericin B = 1, isavuconazole = 4, micafungin >8, itraconazole >16, voriconazole >16, and posaconazole >16. To evaluate the interactions between antifungal drugs, the activity of the posaconazole in combination with terbinafine were also evaluated M. wolfii using agar diffusion test. A combination of posaconazole and terbinafine, significantly inhibited the mycelial growth, which indicates synergism. The patient’s treatment was started on terbinafine in combination with posaconazole. On several follow-up examinations following treatment on day 30, 90 and 120, the infection had not recurred.ConclusionThe species of M. wolfii a is an environmental mold belongs to the order Mortierellales within the subphylum Mortierellomycotina of Kingdom Fungi. This fungus has been mostly associated with fungal infections leading to abortion in dairy cows feeding moldy hays and ensilage.Although posaconazole exhibited high MICs against M. wolfii, our in vitro combination study demonstrated that posaconazole and terbinafine combined are significantly more potent than either drug alone. As a suggestion, combination therapy could provide an option for the treatment of severe cases of M. wolfii in patients with underlying primary immunodeficiencies.As molecular identification and sequencing techniques continue to develop and become more available, we will likely see more diverse pathogens emerge in patients with underlying primary immunodeficiencies. In this current case. Additional study is warranted to explore insight into human immunity and the efficacy of combination therapy against rare fungal species in CGD patients.