Voriconazole Compared with Liposomal Amphotericin B for Empirical Antifungal Therapy in Patients with Neutropenia and Persistent Fever

Background Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections. Antifungal triazoles offer a potentially safer and effective alternative. Methods In a randomized, international, multicenter trial, we compared voriconazole, a new second-generation triazole, with liposomal amphotericin B for empirical antifungal therapy. Results A total of 837 patients (415 assigned to voriconazole and 422 to liposomal amphotericin B) were evaluated for success of treatment. The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B (95 percent confidence interval for the difference, –10.6 to 1.6 percentage points); these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors. There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal amphotericin B (8 [1.9 percent] vs. 21 [5.0 percent], P=0.02). The voriconazole group had fewer cases of severe infusion-related reactions (P\u3c0.01) and of nephrotoxicity (P\u3c0.001). The incidence of hepatotoxicity was similar in the two groups. Patients receiving voriconazole had more episodes of transient visual changes than those receiving liposomal amphotericin B (22 percent vs. 1 percent, P\u3c0.001) and more hallucinations (4.3 percent vs. 0.5 percent, P\u3c0.001). Parenteral voriconazole was changed to the oral formulation in 22 percent of the voriconazole group, with a reduction in the mean duration of hospitalization by one day in all patients (P=0.17) but by two days in patients at high risk (P=0.03). Conclusions Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever. (N Engl J Med 2002;346:225-34.

Acute Pneumonia

Book chapter discussing the epidemiology, etiology, diagnosis, treatment, and prevention of acute pneumonia

Primary Cutaneous Cryptococcosis Treated with Debridement and Fluconazole Monotherapy in an Immunosuppressed Patient: A Case Report and Review of the Literature

Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC) in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy

Clinical research in the lay press: irresponsible journalism raises a huge dose of doubt

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