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Invasive fungal infections, most commonly candidiasis or aspergillosis, are a major cause of morbidity and mortality among patients with neutropenia. Difficulty in diagnosing invasive fungal infections in these patients complicates decisions regarding pharmacotherapy. Because of the difficult diagnosis and the significant morbidity and mortality of fungal infections in patients with neutropenia, systemic antifungal agents are used as empiric antifungal therapy in patients with febrile neutropenia who are not responding to antibacterial therapy. The pharmacotherapy of invasive fungal infections has evolved rapidly within the past several years as numerous antifungal agents--different formulations of amphotericin B, azoles, and echinocandins--have become available for use as empiric antifungal therapy in patients with febrile neutropenia. Various levels of evidence support the use of these agents for this indication. Their use is limited, however, by drug intolerance, drug interactions, adverse-event profiles, and limited activity with some mold species. Thus, considerations for selecting an antifungal drug for empiric use in patients with febrile neutropenia should include the epidemiology of fungal infections in the individual patient's institution and the specific clinical circumstances of the patient.

Objective: To review the data supporting available antifungal agents and compare regimens utilized to prevent fungal infection in lung transplant recipients., Data Sources: Literature retrieval was accessed through MEDLINE (1950 through October 2009) and United Network for Organ Sharing online database (available data through October 2009), using the terms lung transplantation, prophylaxis, and fungal infection. In addition, reference citations from publications identified were reviewed., Study Selection and Data Extraction: All articles or related abstracts in English identified from the data sources above were evaluated. Literature including adult lung transplant recipients who received systemic antifungal prophylaxis to prevent invasive fungal infections (IFIs) was included in the review., Data Synthesis: IFIs after lung transplantation remain a common postoperative problem and are associated with high mortality. The lung is the most vulnerable solid organ to be transplanted, as it is the main organ responsible for gas exchange and therefore the high risk for pulmonary-related IFIs. It is most susceptible to developing an IFI, as it serves as a medium for organisms traveling from air to human tissue, potentially causing life-threatening infections. Such infections typically involve Candida and Aspergillus spp. and tend to occur within the first 12 months after transplant. Although there has been an increase in lung transplants performed over the past decade, no standard antifungal prophylactic regimen exists. Literature describing antifungals used to prevent IFI after transplant is scarce, which may be due to a lack of consistency in regimens used between transplant centers. Several regimens have been described utilizing different antifungal agents as both monotherapy and combination therapy. The majority of the literature reviewed here describes aerosolized amphotericin B formulations and azole antifungals demonstrating an overall decreased risk of fungal infection after lung transplantation. It has become the standard of practice to initiate some form of antifungal prophylaxis in these patients., Conclusions: The risk of fungal infection after lung transplant is multifactorial and optimal prophylactic regimens should include agents with adequate activity against the most pathogenic fungi.

Invasive fungal infections carry significant morbidity and mortality. Candida species have become one of the most frequent causes of bloodstream infections, and infections caused by molds such as Aspergillus are becoming more frequent in immunocompromised patients. As this population grows, more invasive fungal infections can be anticipated. In the past, treatment options have been limited for many of these infections due to toxicity and efficacy concerns with the available antifungals. Fortunately, the past few years have brought exciting developments in antifungal pharmacotherapy. Lipid-based formulations of amphotericin B were introduced in the 1990s to attenuate adverse effects caused by amphotericin B deoxycholate (Fungizone, Bristol-Myers Squibb). Most recently, the echinocandins have been added to our antifungal regimen with the introduction of caspofungin (Cancidas, Merck and Co.) and voriconazole (Vfend, Pfizer), a new triazole, has come to market. The introduction of the echinocandins has invigorated the discussion about combination antifungal therapy. Evidence-based studies using these new agents are accumulating, and they are assuming important roles in the pharmacotherapy of invasive fungal infections in seriously ill and complex patients.

The incidence of invasive mould infections is increasing and is associated with significant morbidity and mortality. Among the most prevalent of these infections are those caused by Aspergillus and Fusarium species. Invasive disease caused by moulds frequently presents as a pulmonary infection, but haematogenous infection can occur. Some moulds cause cutaneous disease through either direct inoculation of the skin or secondary spread to the skin after dissemination from another body site. Early diagnosis can often be difficult and, unfortunately, diagnosis occurs late in the course of illness in many cases. Treatment options have historically been limited by the need for intravenous administration (amphotericin B), significant toxicities (amphotericin B), lack of reliable in vitro activity (e.g., amphotericin B in Fusarium and Scedosporium apiospermum infections) and relative lack of clinical experience with newer agents. The recent approval of voriconazole (Vfend, Pfizer) introduces a treatment option that demonstrates both in vitro and in vivo activity against a variety of moulds. With the recent development of the new echinocandin class of antifungal agents and newer broad-spectrum azole antifungal agents with in vitro mould activity, there is a renewed emphasis on fungal treatment strategies. Antimould therapy presents challenges in adverse effect avoidance and management, drug interactions and pharmacoeconomic considerations. Furthermore, combination therapy is being explored with these various new antifungal agents. The administration of an optimal fungicidal therapy early in the course of the illness and control of the underlying disease are vital to prevent complications and mortality from these tenacious mycoses.