Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Fusarium metavorans sp. nov.: The frequent opportunist 'FSSC6'.

The Fusarium solani species complex (FSSC) is the most common group of fusaria associated with superficial and life-threatening infections in humans. Here we formally introduce Fusarium metavorans sp. nov., widely known as FSSC6 (Fusarium solani species complex lineage 6), one of the most frequent agents of human opportunistic infections. The species is described with multilocus molecular data including sequences of internal transcribed spacer region (ITS), portions of the translation elongation factor 1-a gene (TEF1), and the partial RNA polymerase II gene (rPB2). A phylogenetic approach was used to evaluate species delimitation. Topologies of the trees were concordant. Phylogenetic analyses suggest that the FSSC consists of three major clades encompassing a large number of phylogenetic species; Fusarium metavorans corresponds to phylogenetic species 6 within FSSC clade 3. The species has a global distribution and a wide ecological amplitude, also including strains from soil and agents of opportunistic plant disease; it was also isolated from the gut of the wood-boring cerambycid beetle Anoplophora glabripennis.

Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

[This corrects the article DOI: 10.3389/fmicb.2018.00516.].

Pseudomonas oryzihabitans Infected Total Hip Arthroplasty.

Pseudomonas oryzihabitans is a saprophytic gram-negative microorganism usually found in damp environments, only occasionally responsible for human pathology. Infection mainly occurs in malnourished, immunocompromised individuals with indwelling catheters. There is no previous published record of infection after joint arthroplasty. To enhance the literature, in this article we report a patient with a Pseudomonas oryzihabitans infected total hip arthroplasty, and discuss the diagnosis and management of this unusual infection.

An unusual cutaneous tumor: African histoplasmosis following mudbaths: case report and review.

African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area.

Zygomycosis in Immunocompromised non-Haematological Patients.

Zygomycoses caused by fungi of the mucorales order (mucormycoses) are emerging fungal diseases with a high fatality rate. The most important risk factors include neutropenia or functional neutropenia, diabetic ketoacidosis, iron overload, major trauma, prolonged use of corticosteroids, illicit intravenous drug (ID) use, neonatal prematurity, malnourishment, and maybe a previous exposure to antifungal agents with no activity against zygomycetes, such as voriconazole and echinocandins.A high index of suspicion is crucial for the diagnosis, as prompt and appropriate management can considerably reduce morbidity and mortality. Suspicion index can be increased through recognition of the differential patterns of clinical presentation. In the non- haematological immunocompromised patients, mucormycosis can manifest in various clinical forms, depending on the underlying condition: mostly as rhino-orbital or rhino-cerebral in diabetes patients, pulmonary infection in patients with malignancy or solid organ transplantation, disseminated infection in iron overloaded or deferoxamine treated patients, cerebral - with no sinus involvement - in ID users, gastrointestinal in premature infants or malnourishment, and cutaneous after direct inoculation in immunocompetent individuals with trauma or burns.Treating a patient's underlying medical condition and reducing immunosuppression are essential to therapy. Rapid correction of metabolic abnormalities is mandatory in cases such as uncontrolled diabetes, and corticosteroids or other immunosuppressive drugs should be discontinued where feasible. AmphotericinB or its newer and less toxic lipid formulations are the drugs of choice regarding antifungal chemotherapy, while extensive surgical debridement is essential to reduce infected and necrotic tissue. A high number of cases could be prevented through measures including diabetes control programmes and proper pre- and post-surgical hygiene.