Antifungal Effect of All-trans Retinoic Acid against Aspergillus fumigatus In Vitro and in a Pulmonary Aspergillosis In Vivo Model.

Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of subinhibitory concentration of amphotericin B (AmB) and posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to posaconazole. Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal heat shock protein 90 (Hsp90) expression and Hsp90-related genes. ATRA treatment reduced mortality in a model of IPA in vivo Those findings suggest ATRA as a suitable fungistatic agent that can also reduce dosage and adverse reactions of classical antifungal drugs and add to the development of new therapeutic strategies against IPA and systemic fungal infections.

Considerations on antimicrobial prophylaxis in patients with lymphoproliferative diseases: A SEIFEM group position paper.

The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections.

Lack of efficacy of imiquimod in patients with basal cell carcinoma previously treated with rituximab for B cell lymphoma: two case reports.

BACKGROUND: Non-Hodgkin lymphomas are a heterogeneous group, which involve either B or T lymphocytes. The most used treatment is a chemotherapy regimen, which includes cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone combined with rituximab - a monoclonal antibody specific for CD20 - an antigen expressed on B lymphocyte membrane. Nonmelanoma skin cancers are the most common forms in patients who have lymphomas. CASE PRESENTATION: We reported the cases of two Caucasian men affected by non-Hodgkin disease, treated with chemotherapy and rituximab. After treatment, they both presented superficial basal cell carcinoma and we prescribed imiquimod 5 % cream. Unfortunately, the drug was not effective in either patient and the tumors were excised. CONCLUSIONS: We speculated about the effect of rituximab on B lymphocytes, on a particular population of T cells and on antigen-presenting dendritic cells that may have determined a lower expression of some surface antigens involved in antigen presentation. These cells are the specific targets of imiquimod to promote skin cancer cells apoptosis. A lack of action by imiquimod on skin cancer after treatment with rituximab is likely due to its transitory inhibitory effects on lymphocytes and Langherans cells. Further studies could be useful to understand the mechanism behind the lack of response.