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Empirical antifungal therapy
1Service de Médecine Interne et Laboratoire d'Investigation Clinique H.J. Tagnon, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, 1, rue Héger-Bordet, 1000 Bruxelles, Belgium. jean.klastersky@bordet.be
Abstract:
The number of fungal infections is increasing, particularly in patients with cancer, and represent a major problem given the relatively poor response rates, especially for aspergillosis, and the high cost. Empirical therapy has become an accepted practice as delay in instituting therapy is clearly associated with increased morbidity and mortality. In terms of efficacy for the management of persistent febrile neutropenic patients, there is no convincing evidence that conventional amphotericin B (ampho B) is inferior to any other agent; the lipid formulations of ampho B provide similar efficacy with lower toxicity but at a much higher cost. Fluconazole is equivalent to ampho B, provided patients at high risk of aspergillus infections are excluded. Itraconazole and voriconazole, as empirical therapies, are equivalent to conventional ampho B and liposomal ampho B, respectively; toxicity is definitely lower and voriconazole is more effective at preventing breakthrough fungal infections.
Insights
Fungal infections in cancer patients are rising, necessitating effective empirical therapies. Newer antifungals like voriconazole offer lower toxicity and better prevention of breakthrough infections compared to older agents.
Area of Science:
- Mycology
- Oncology
- Infectious Diseases
Background:
- Increasing incidence of invasive fungal infections (IFIs), especially in cancer patients.
- Significant morbidity, mortality, and high costs associated with IFIs, particularly aspergillosis.
- Empirical therapy is crucial due to delayed treatment correlating with worse outcomes.
Purpose of the Study:
- To evaluate the efficacy and toxicity of various empirical antifungal agents for febrile neutropenic patients.
- To compare conventional amphotericin B with newer antifungal agents.
- To assess the role of fluconazole, itraconazole, and voriconazole in empirical antifungal therapy.
Main Methods:
- Comparative efficacy and toxicity analysis of antifungal agents.
- Focus on persistent febrile neutropenia in cancer patients.
- Review of clinical evidence for conventional amphotericin B, lipid formulations, fluconazole, itraconazole, and voriconazole.
Main Results:
- Conventional amphotericin B shows comparable efficacy to newer agents but with higher toxicity.
- Lipid formulations of amphotericin B offer similar efficacy with reduced toxicity but increased cost.
- Fluconazole is effective if high-risk Aspergillus cases are excluded.
- Itraconazole and voriconazole demonstrate equivalent efficacy to conventional and liposomal amphotericin B, respectively, with lower toxicity.
- Voriconazole shows superior efficacy in preventing breakthrough fungal infections.
Conclusions:
- Empirical antifungal therapy is vital for managing febrile neutropenia in cancer patients.
- Voriconazole presents a favorable option due to its efficacy, lower toxicity, and preventative capabilities against breakthrough infections.
- Choice of agent should balance efficacy, toxicity, cost, and patient-specific risk factors.
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