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Intravenous Itraconazole in the Management of Fungal Infections in Bone Marrow Transplantation

Intravenous Itraconazole in the Management of Fungal Infections in Bone Marrow Transplantation

The frequency of major fungal infections continues to increase, whether in association with increasing numbers of patients at risk due to under lying disease or its treatment, selection pressures related to increased use of broad-spectrum antimicrobials and repeated courses of such treatments, or a combination of these and other factors. In the bone marrow transplantation (BMT) setting, the most frequent culprits are still Candida and Aspergillus. In some centers, non-albicans Candida species are becoming predominant, perhaps in association with increasing use of fluconazole (Diflucan) prophylaxis. In addition, some reports suggest that A fumigatus cases are being joined by more frequent cases of infection with terreus and other species.

Intravenous (IV) itraconazole (Sporanox) is a promising and important addition to options in treating and preventing fungal infection in BMT patients. Itraconazole possesses some unique features compared with other treatments in that it exhibits a broader spectrum of activity than fluconazole, including activity against Aspergillus and possibly some fluconazole-resistant Candida, and is associated with less toxicity than conventional amphotericin B; IV itraconazole is also less expensive than the liposomal formulations of amphotericin B. How is this new treatment to be adopted into protocols for prevention and treatment?

At a recent roundtable meeting in New York City, we brought together physicians and pharmacy representatives from major treatment centers to discuss profiles of fungal infection and treatment practices at their institutions, characteristics of available antifungal agents, and extant data on the use of itraconazole in fungal prophylaxis and treatment. The articles herein are based on the presentations made by the contributors at that meeting.

Kenneth Rolston, MD, provides an overview of current trends in invasive fungal infection, including information on types of causative organisms encountered at M. D. Anderson Cancer Center. Kieren A. Marr, MD, discusses the rationale for selection among treatment options and the characteristics of optimal or ideal preventive therapy and treatment of confirmed infection; she points out that additional data are needed on the effects of IV itraconazole in the setting of antimold prophylaxis in the BMT population, and that a valuable role in treatment of confirmed infection for itraconazole and other mold-active azoles can be foreseen.

Raymond Muller, RPh, discusses the attributes of the newer additions to treatment options—ie, liposomal amphotericin B, the improved itraconazole oral solution, and IV itraconazole. Michael Potter, MD, PhD, reviews European data on IV itraconazole in the settings of invasive pulmonary aspergillosis, empiric therapy in patients with hematologic malignancy, and on prophylaxis with oral solution itraconazole in hematologic malignancy. He also reviews uses of IV itraconazole in practice in the United Kingdom, which has included switching between oral solution and IV forms in prophylaxis or preemptive treatment, use in high-risk prophylaxis and during mucositis, and in combination with or in place of amphotericin B in documented infection.

Since our meeting in June 2000, several advances in antifungal therapeutics have occurred, and more are anticipated in the near future. In addition to the release of IV itraconazole in March 2000 and its approval for management of neutropenic fever in May 2001, the FDA approved IV caspofungin (Cancidas) for refractory aspergillosis in February 2001. This is the first agent in a new class of antifungals—the echinocandins. Additional studies are underway to further define its role. Other echinocandins such as FK 463 are also being evaluated. Additionally, voriconazole, a novel triazole, is nearing approval in both oral and IV forms. This agent may offer therapeutic advantages in some clinical situations. Other triazole agents—posaconazole and ravuconazole—are in different stages of evaluation.

It is hoped that the articles in this supplement shed some light on the potential utility of intravenous itraconazole, keeping in mind that the epidemiology, diagnosis, and treatment of fungal infections will continue to evolve in the months and years to come.

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