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 optionsie, 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 antifungalsthe 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 agentsposaconazole and ravuconazoleare
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.