Antifungal drugs: What brings the future?

The high burden and growing prevalence of invasive fungal infections (IFIs), the toxicity and interactions associated with current antifungal drugs, as well as the increasing resistance, ask for the development of new antifungal drugs, preferably with a novel mode of action. Also, the availability of oral or once-weekly alternatives would enable ambulatory treatment resulting in an improved patient's comfort and therapy adherence. However, only one new azole and two new posaconazole-formulations were marketed over the last decade. This review focuses on the antifungal drugs in the pipeline undergoing clinical evaluation. First, the newest azole, isavuconazole, with its improved safety profile and reduction in DDIs, will be discussed. Moreover, there are two glucan synthase inhibitors (GSIs) in the antifungal pipeline: rezafungin (CD101), a long-acting echinocandin with an improved stability that enables once weekly administration, and SCY-078, an orally available GSI with efficacy against azole- and echinocandin resistant isolates. A new oral formulation of amphotericin B will also be presented. Moreover, the first representative of a new antifungal class, the orotomides, with a broad spectrum and no cross-resistance with current antifungal classes, will be discussed. Finally, an overview of other antifungals that are still in earlier clinical development phases, is provided.

Acquired factor X deficiency in a multiple myeloma without amyloidosis: a case report.

BACKGROUND: Multiple myeloma is one of the most common hematologic malignancies. Acquired factor X deficiencies are often observed in primary (AL) amyloidosis and rarely in multiple myeloma. OBJECTIVE: We report a case of an acquired factor X deficiency in a patient with a newly diagnosed IgA lambda multiple myeloma, without any evidence of concomitant amyloidosis. METHODS: We present the patient's medical history, clinical and physical examinations, laboratory analysis, and outcome. RESULTS: A 76-year-old male presented at the emergency department with ongoing gingival bleeding. Several analytical problems with blood sample analysis arose, which eventually led to the diagnosis of a multiple myeloma. Further exploration revealed an acquired factor X deficiency, explaining the ongoing bleeding. There was no evidence of concomitant amyloidosis. The multiple myeloma was treated, leading to complete remission of the malignancy and bleeding tendency. CONCLUSION: While coagulopathy is rarely observed in patients diagnosed with multiple myeloma, considering an acquired factor X deficiency becomes relevant when such patient present with bleeding diathesis.

Germline heterozygous SH2B3-mutations and (idiopathic) erythrocytosis: Detection of a previously undescribed mutation.

Erythrocytosis or polycythemia refers to a true or apparent increase in hemoglobin or hematocrit. When no etiology of erythrocytosis is identified, people are diagnosed with "idiopathic erythrocytosis" (IE). The identification of new contributing genes has recently improved the diagnostic workup of IE. As such mutations within the SH2B3 gene, which codes for the LNK protein and negatively regulates the JAK-STAT pathway, have been identified in cases diagnosed as IE. This reports describes the presence of a previously undescribed germline SH2B3 variant p.(Thr335ArgfsTer4) within IE and emphasizes the advantages of gene panel sequencing as second step in the diagnostic work-up.