Fighting fungal infections

New antifungal therapies may help tame this growing problem and improve patient outcomes

Candida, Aspergillus, Fusarium ... Fungal pathogens are a major cause of healthcare-associated infections in the United States. The recent outbreak of Fusarium among contact lens wearers and the spread of mold and fungus from Hurricane Katrina have brought increased attention to the problem of fungal infections.

The introduction of more advanced treatments for critical illnesses, hematological conditions, and malignancies, which has been embraced by both clinicians and patients, has "resulted in a change in the epidemiology of nosocomial fungal infections," said Tamira Mullarkey, Pharm.D., clinical pharmacist at Clara Maass Medical Center in Belleville, N.J.

Fortunately, the armamentarium for treating severe fungal infections keeps growing with the introduction of broad-spectrum antifungals. Mullarkey advocates that pharmacists be familiar with the spectrum of activity and properties of these newer agents, in order to help fight fungal infections.

Antifungal therapy for invasive infections remains largely empiric. According to Esther Hilburger, Pharm.D., clinical pharmacy specialist at Sentara Careplex Hospital in Hampton, Va., recognizing a patient's risk factors for fungal infections and relying on his or her clinical presentation are essential in diagnosing a fungal infection. "Selecting antifungal drugs requires knowledge of the local pathogens. Clinicians should be familiar with their institution's fungal prevalence patterns," she advised.

The azole antifungal agents

Leading a group of broad-spectrum triazole antifungals is voriconazole (Vfend, Pfizer). Available in both intravenous (IV) and oral formulations, voriconazole works by inhibiting fungal membrane synthesis through the inhibition of ergosterol formation. It offers Aspergillus coverage and has improved activity against Candida species, "most notably against the non-albicans species," said Mullarkey.

Another extended-spectrum antifungal on the horizon is posaconazole (Noxafil, Schering-Plough). In vitro and in vivo studies show that posaconazole has activity against Candida species, including fluconazole-resistant non-albicans strains, Cryptococcus neoformans, and Aspergillus species. It has recently been cleared for priority review by the Food & Drug Administration for prevention of serious invasive fungal infections in high-risk patients.

Posaconazole is available for oral use in clinical studies, and greater drug exposure has been seen when it is given as an oral suspension than as a tablet. Furthermore, the absorption of posaconazole suspension is enhanced by coadministration with food or liquid nutritional supplements. No IV formulation of posaconazole has yet been used in clinical trials, which Mullarkey views as a limitation of the drug, when compared with voriconazole.