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Antifungal prophylaxis for allogeneic haematopoietic stem-cell transplant (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs) and be well tolerated. This prospective, randomized, open-label, multicentre study compared the efficacy and safety of voriconazole (234 patients) versus itraconazole (255 patients) in alloHCT recipients. The primary composite endpoint, success of prophylaxis, incorporated ability to tolerate study drug for ≥ 100 d (with ≤ 14 d interruption) with survival to day 180 without proven/probable IFI. Success of prophylaxis was significantly higher with voriconazole than itraconazole (48·7% vs. 33·2%, P < 0·01); more voriconazole patients tolerated prophylaxis for 100 d (53·6% vs. 39·0%, P < 0·01; median total duration 96 vs. 68 d). The most common (>10%) treatment-related adverse events were vomiting (16·6%), nausea (15·8%) and diarrhoea (10·4%) for itraconazole, and hepatotoxicity/liver function abnormality (12·9%) for voriconazole. More itraconazole patients received other systemic antifungals (41·9% vs. 29·9%, P < 0·01). There was no difference in incidence of proven/probable IFI (1·3% vs. 2·1%) or survival to day 180 (81·9% vs. 80·9%) for voriconazole and itraconazole respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis after alloHCT, based on differences in the primary composite endpoint. Voriconazole could be given for significantly longer durations, with less need for other systemic antifungals., (2011 Blackwell Publishing Ltd.)

The objective of this study was to evaluate the triazole anti-fungal agent, voriconazole, as therapy for systemic Penicillium marneffei infections in patients with advanced HIV infection. Patients with systemic P. marneffei infection were enrolled into a study of voriconazole for the treatment of less common, emerging, or refractory fungal infections. Patients were eligible for inclusion in the study on the basis that no anti-fungal agents have received regulatory approval specifically for P. marneffei infections. Patients were treated in the hospital setting with intravenous voriconazole (6 mg/kg every 12 hours on Day 1 and then 4 mg/kg every 12 hours for at least 3 days, after which patients could switch to oral therapy at 200 mg twice a day) or as outpatients with oral voriconazole (400 mg twice a day on Day 1 and then 200 mg twice a day) for a maximum of 12 weeks. Eleven patients received treatment with voriconazole. Two received short courses of intravenous therapy followed by the oral formulation; nine were treated with oral voriconazole only. At the end of therapy, eight of the nine evaluable patients had favorable response to therapy, based on mycological and clinical findings. There were no relapses of P. marneffei infection in the six patients who were seen at follow-up within 4 weeks of the end of therapy. Treatment with voriconazole was well tolerated, with no discontinuations caused by drug-related adverse events. The results of this study suggest that voriconazole is an effective, well-tolerated, and convenient option for the treatment of systemic infections with P. marneffei.

Invasive Fusarium infections cause high mortality. Fosmanogepix, a first-in-class antifungal agent, has potent activity against Fusarium. A patient with acute leukemia with invasive fusariosis, probably involving the central nervous system and caused by Fusarium lactis resistant to currently available antifungal agents, was cured of her infection with fosmanogepix. Fosmanogepix was well tolerated. [ABSTRACT FROM AUTHOR]

Episodes of invasive aspergillosis (IA) recruited to the voriconazole trial were reclassified according to the revised EORTC/MSG definitions. The efficacy of voriconazole was confirmed for possible, probable, and proven IA and was still better than found for the comparator arm.Background. Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions.Methods. The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged.Results. Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%–45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%–36.7%), suggesting that possible cases are true IA.Conclusions. Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA. [ABSTRACT FROM PUBLISHER]

The article discusses the results of a clinical study that was conducted to investigate the causes of death among patients who undergone treatment for invasive aspergillosis (IA). Of the total 277 patients participated, 98 died during the 12-week course of the study. It mentions that voriconazole was assigned to 144 patients while amphotericin B was recieved by the remaining 133 patients.

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 [3 6%] 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. [ABSTRACT FROM AUTHOR]

Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 504570360f the overall cohort; specifically, successful outcomes were observed in 4760303560f patients whose infections failed to respond to previous antifungal therapy and in 6860303210f patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7 0.000000or aspergillosis, 57.5 0.000000or candidiasis, 38.9 0.000000or cryptococcosis, 45.5 0.000000or fusariosis, and 30 0.000000or scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for < 1060304100f patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections. [ABSTRACT FROM AUTHOR]