Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial
Abstract
Background Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients.Methods Non-neutropenic patients with a positive blood culture for a species of candida and clinical evidence of infection were enrolled. Patients were randomly assigned, in a 2:1 ratio, either voriconazole (n=283) or amphotericin B followed by fluconazole (n=139). The primary efficacy analysis was based on clinical and mycological response 12 weeks after the end of treatment, assessed by an independent data-review committee unaware of treatment assignment.Findings Of 422 patients randomised, 370 were included in the modified intention-to-treat population. Voriconazole was non-inferior to amphotericin B/fluconazole in the primary efficacy analysis, with successful outcomes in 41% of patients in both treatment groups (95% CI for difference -10.6% to 10.6%). At the last evaluable assessment, outcome was successful in 162 (65%) patients assigned voriconazole and 87 (71%) assigned amphotericin B/fluconazole (p=0.25). Voriconazole cleared blood cultures as quickly as amphotericin B/fluconazole (median time to negative blood culture, 2.0 days). Treatment discontinuations due to all-cause adverse events were more frequent in the voriconazole group, although most discontinuations were due to non-drug-related events and there were significantly fewer serious adverse events and cases of renal toxicity than in the amphotericin B/fluconazole group.Interpretation Voriconazole was as effective as the regimen of amphotericin B followed by fluconazole in the treatment of candidaemia in non-neutropenic patients, and with fewer toxic effects.Relevance to practice There are several options for treatment of candidaemia in non-neutropenic patients, including amphotericin B, fluconazole, voriconazole, and echinocandins. Voriconazole can be given both as initial intravenous treatment and as an oral stepdown agent.
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In 1 study, patients were allowed to step down to oral fluconazole therapy in as few as 3 to 7 days after intravenous therapy with amphotericin.
“In 1 study, patients were allowed to step down to oral fluconazole therapy in as few as 3 to 7 days after intravenous therapy with amphotericin.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [106]
Voriconazole was as effective as amphotericin B followed by fluconazole for the treatment of candidemia.
“Voriconazole, a broad spectrum triazole active against filamentous fungi as well as Candida species, was as effective as amphotericin B followed by fluconazole for the treatment of candidemia [29].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [29]
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- Authors
- Kullberg, B., Sobel, J., Ruhnke, M., Pappas, P., Viscoli, C., Rex, J., Cleary, J., Rubinstein, E., Church, L., Brown, J., Schlamm, H., Oborska, I., Hilton, F., & Hodges, M.
- Affiliations
- Radboud University Nijmegen (NL)
- Humboldt-Universität zu Berlin (DE)
- Ospedale Policlinico San Martino (IT)
- Tel Aviv University (IL)
- Medical University of South Carolina (US)
- University of the Witwatersrand (ZA)
- Pfizer (United States) (US)
- Corresponding author
- Kullberg, BJ
- ORCID
- Ruhnke, M
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 366
- Issue
- 9495
- Pages
- 1435-1442
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2104218588
- Cited by
- 521
- References
- 22
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 18 · 2020: 10 · 2019: 14 · 2018: 17 · 2017: 14 · 2016: 10 · 2015: 22 · 2014: 22 · 2013: 25 · 2012: 35
- FWCI
- 36.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- candidemia, voriconazole, amphotericin B, fluconazole, non-neutropenic patients, antifungal therapy, non-inferiority, nephrotoxicity, adverse events, echinocandins, invasive candidiasis, oral step-down therapy, echinocandin resistance
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Amphotericin B, Antifungal Agents, Candidiasis, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Pyrimidines, Triazoles, Fluconazole, Treatment Outcome, APACHE, Voriconazole
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