Abstract
Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Transplant patients are at risk for such invasive fungal infections. The most common invasive fungal infections are invasive candidiasis in the SOT and invasive aspergillosis in the HSCT. In this article, we will discuss the epidemiology of invasive fungal infections in the transplant recipients and susceptibility patterns of the fungi associated with these infections. Additionally, the pharmacology and clinical efficacy of the new antifungal, isavuconazole, and the new posaconazole formulations will be reviewed. Isavuconazole is a new extended-spectrum triazole that was recently approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. Posaconazole oral suspension solution has shown some limitations in the setting of fasting state absorption, elevated gastrointestinal pH, and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide additional treatment options by reducing interpatient variability and providing flexibility in these set of critically ill patients. This review will detail these most recent studies.
Highlights
Invasive fungal infections (IFI) are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients
The delayed-release tablet cannot be crushed or chewed as this may damage the integrity of the pH-sensitive matrix and, the pharmacokinetics may be altered; this may limit its use among patients who cannot take medications orally and enteral administration is preferred [11]
All posaconazole formulations are approved for the prophylaxis of invasive aspergillosis and candidiasis among high risk patients (e.g., hematopoietic stem cell transplant recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy)
Summary
Invasive fungal infections (IFI) are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and mucormycosis (2%) [3]. Aspergillus species (44%) and C. glabrata (33%) was more common than C. albicans (20%) in contrast to SOT recipients. The majority of these patients had received allogeneic transplants (78%). Some of its characteristics include linear dose-proportional pharmacokinetics, IV, and oral formulations allowing therapeutic streamlining, once daily dosing, absence of nephrotoxic solubilizing agents and excellent oral bioavailability independent of meal status and gastric acidity Both agents, posaconazole and isavuconazole are active against non-C. albicans spp., Aspergillus spp. and non-Aspergillus molds. We will review the data that is currently available for the new formulations of posaconazole and the newly approved azole, isavuconazole
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