Sarocladium and Acremonium infections: New faces of an old opportunistic fungus.

The genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses. We also aim to summarise and discuss the data currently available on their antifungal susceptibility, emphasising the promising results obtained with voriconazole as well as their impact in terms of animal infections.

Improvement of the pharmacokinetic/pharmacodynamic relationship in the treatment of invasive aspergillosis with voriconazole. Reduced drug toxicity through novel rapid release formulations.

Voriconazole (VCZ) is currently the first-line treatment for invasive aspergillosis, although the doses are limited by its poor solubility and high hepatic toxicity. The aim of this study was to develop a solid self-dispersing micellar system of VCZ to improve the pharmacokinetic/pharmacodynamic (PK/PD) relationship and reduce hepatotoxicity. In this work, solid micellar systems of VCZ are formulated with different polysorbate 80 ratios using mannitol as a hydrophilic carrier. The novel micellar systems were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dissolution studies. Self-dispersing micellar systems reduced VCZ crystallinity, leading to an improvement in its dissolution rate. The in vitro susceptibility test also revealed that the most common microorganisms in invasive aspergillosis exhibited low minimum inhibitory concentration (MIC) values for micellar systems. Pharmacokinetic studies indicated an improvement in bioavailability for MS-1:3:0.05, and changes in its biodistribution to different organs. MS-1:3:0.05 showed an increased concentration in lungs and a significant decrease in VCZ accumulated in the liver.

Antifungal susceptibility of Saccharomyces cerevisiae and therapy in a murine model of disseminated infection.

BACKGROUND: The incidence of systemic infections by Saccharomyces cerevisiae has increased in recent years, especially among immunocompromised patients. Amphotericin B, voriconazole or echinocandins have been used with favorable outcome against systemic infections by this fungus. However, clinical experience is limited and no in vivo studies have been conducted. AIMS: We evaluated the in vitro activity of nine antifungal compounds against S.cerevisiae and the in vivo efficacy of those three antifungals showing the highest in vitro activity by using a murine model of systemic infection. METHODS: Minimal inhibitory concentrations (MICs) were determined by the microdilution method against three strains of S. cerevisiae. After intravenous infection with 5×107 CFUs, animals received liposomal amphotericin B (5mg/kg), voriconazole (25mg/kg) or anidulafungin (5mg/kg). Treatment efficacy was assessed by determining of CFUs/g in liver, kidney, brain, lung and spleen. RESULTS: 5-Fluorocytosine was the most in vitro active compound followed by amphotericin B, voriconazole and anidulafungin. The in vivo study showed that liposomal amphotericin B was the most effective drug driving highest fungal clearance. CONCLUSIONS: All treatments reduced the fungal load in comparison to the control group, being liposomal amphotericin B the most effective drug followed by anidulafungin and finally voriconazole.