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

The frequency of major fungal infections continues toincrease, whether in association with increasing numbers of patients at risk dueto under lying disease or its treatment, selection pressures related toincreased use of broad-spectrum antimicrobials and repeated courses of suchtreatments, or a combination of these and other factors. In the bone marrowtransplantation (BMT) setting, the most frequent culprits are still Candida andAspergillus. In some centers, non-albicans Candida species are becomingpredominant, perhaps in association with increasing use of fluconazole (Diflucan)prophylaxis. In addition, some reports suggest that A fumigatus cases are beingjoined by more frequent cases of infection with terreus and other species.

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

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

Kenneth Rolston, MD, provides an overview of current trends in invasivefungal infection, including information on types of causative organismsencountered at M. D. Anderson Cancer Center. Kieren A. Marr, MD, discusses therationale for selection among treatment options and the characteristics ofoptimal or ideal preventive therapy and treatment of confirmed infection; shepoints out that additional data are needed on the effects of IV itraconazole inthe setting of antimold prophylaxis in the BMT population, and that a valuablerole in treatment of confirmed infection for itraconazole and other mold-activeazoles can be foreseen.

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

Since our meeting in June 2000, several advances in antifungal therapeuticshave occurred, and more are anticipated in the near future. In addition to therelease of IV itraconazole in March 2000 and its approval for management ofneutropenic fever in May 2001, the FDA approved IV caspofungin (Cancidas) forrefractory aspergillosis in February 2001. This is the first agent in a newclass of antifungals—the echinocandins. Additional studies are underway tofurther define its role. Other echinocandins such as FK 463 are also beingevaluated. Additionally, voriconazole, a novel triazole, is nearing approval inboth oral and IV forms. This agent may offer therapeutic advantages in someclinical situations. Other triazole agents—posaconazole and ravuconazole—arein different stages of evaluation.

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