Aspergillus pseudodeflectus: a new human pathogen in liver transplant patients

Abstract

BackgroundLiver transplant recipients are at high risk of developing invasive aspergillosis and in particular by Aspergillus fumigatus which is the most commonly encountered species in this population. Other non-fumigatus Aspergillus species with reduced susceptibility to antifungal drugs can also be involved. Accurate identification associated to antifungal susceptibility testing is essential for therapy adjustment. We report a case of invasive pulmonary aspergillosis due to Aspergillus pseudodeflectus in a liver transplant recipient. To our knowledge, this is the first reported case of invasive aspergillosis due to this species with a reduced susceptibility to azoles.Case presentationA 64 year-old woman with drug-induced fulminant hepatitis underwent liver transplantation. Prophylactic treatment with caspofungin was introduced due to aspergillosis risk factors consisting in hemodialysis and fulminant hepatitis. Six weeks after transplantation, CT scan showed a right pulmonary opacity associated with an increase of galactomannan (index 5.4). Culture of BAL grew with several colonies of Aspergillus sp. The diagnosis of invasive aspergillosis was probable according to the EORTC criteria. The antifungal susceptibility tests (Etest®) revealed low MICs to echinocandins and amphotericin B) but high MICs to azoles. After these results, voriconazole was switched to liposomal amphotericin B. The patient died one month after diagnosis from a refractory septic shock with multiple organ failure. A molecular identification of isolate, based on partial β-tubulin and calmodulin genes, was performed and identified A. pseudodeflectus.ConclusionsOur case raises the question of pathogenicity of this species, which belongs to Aspergillus section Usti and is genetically and morphologically very close to Aspergillus calidoustus that was previously reported in human transplant recipients.

Fungal Infections in Liver Transplant Recipients

“…A variety of Aspergillus species have been associated with infection in liver transplant recipients. The most common infecting Aspergillus species are Aspergillus fumigatus (73%), Aspergillus flavus (14%), and Aspergillus terreus (8%) [ 24 ], but rare species are also reported to cause invasive infections with significant morbidity [ 28 ].…”

Invasive aspergillosis in liver transplant recipients

“…Matrix‐assisted laser desorption ionization‐time of flight mass spectrometry is a tool that has shown its value for the identification of filamentous fungi where the concordance with molecular identification by sequencing reaches more than 98% 136 . The importance of species identification is major due to the differences in sensitivity to antifungal agents between species 137 . In addition, in the case of Aspergillus isolation, the determination of MICs for azole antifungals is relevant due to the increase in strains carrying azole resistance mutations 136 – 139 .…”

“…136 The importance of species identification is major due to the differences in sensitivity to antifungal agents between species. 137 In addition, in the case of Aspergillus isolation, the determination of MICs for azole antifungals is relevant due to the increase in strains carrying azole resistance mutations. [136][137][138][139] Culture does not distinguish colonization from infection in a non-sterile site (e.g., lung), so other non-culture-based biological tests are needed in this case.…”

Clinical Relevance and Characteristics of Aspergillus calidoustus and Other Aspergillus Species of Section Usti

“…Actually, most cases of human infections that were attributed to A. ustus in the literature, were secondarily reassigned to a novel distinct species, A. calidoustus, which is able to grow at 37 • C [14]. Two other closely related species, A. pseudodeflectus and A. granulosus, are also thermotolerant at human body temperature and were also found to be able to cause invasive infections in humans [11,[15][16][17]. A. ustus sensu stricto was also isolated from a patient with aspergillosis localized to the skin and soft tissue [11].…”