Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome.

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Patterson TF, Boucher HW, Herbrecht R, Denning DW, Lortholary O, Ribaud P, Rubin RH, Wingard JR, DePauw B, Schlamm HT, Troke P, Bennett JE

Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome.

Clin Infect Dis. 2005 Nov 15;41(10):1448-52. Epub 2005 Oct 13.

PubMed ID
16231256 [ View in PubMed
]
Abstract

BACKGROUND: In a previous randomized trial of voriconazole versus amphotericin B deoxycholate for primary therapy of invasive aspergillosis, voriconazole demonstrated superior efficacy and better survival. In that trial, treatment with voriconazole or amphotericin B deoxycholate could be followed with other licensed antifungal therapies (OLAT). Here, we report the impact of OLAT on the outcome of patients with invasive aspergillosis. METHODS: Data on dose, duration, and the reason for switching to the first OLAT were analyzed, and outcome at week 12 was assessed. RESULTS: Fewer patients in the voriconazole group (52 [36%] of 144) switched to OLAT, compared with patients in the amphotericin B deoxycholate group (107 [80%] of 133). Lipid formulations of amphotericin B were the most common OLAT (38% of patients). Switches were made because of intolerance or insufficient response in 70% for patients in the amphotericin B deoxycholate group, compared with 24% of patients in the voriconazole group. Favorable responses to OLAT in the amphotericin B deoxycholate group occurred in only 19% of patients with initial insufficient response and 38% of patients with intolerance. Salvage therapy with a lipid formulation of amphotericin B after initial treatment with amphotericin B deoxycholate was successful for only 30% of patients (14 of 47). Treatment success among patients randomized to receive amphotericin B, including those whose treatment was switched to OLAT, was 32%, compared with 55% among patients who received voriconazole alone (P<.001). CONCLUSIONS: This study highlights the limited efficacy of salvage antifungal therapy, including therapy with lipid formulations of amphotericin B, and demonstrates the importance of effective initial therapy in invasive aspergillosis.

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