Title : Effect of Posaconazole compared to other antifungal drugs in survival & prevention of infection in patients with haematological malignancy: A systematic review
Abstract:
Introduction: Patients with acute leukemia who experience neutropenia after intensive chemotherapy have a high risk of developing Invasive Fungal Infections (IFIs), which can be life threatening. Although diagnostics and supportive care have been enhanced, IFIs continue to be a major problem. Therefore, prophylaxis with an antifungal agent is a vital part of management. This Systematic Review examined the effectiveness of Posaconazole vs. other antifungal agents for the prevention of IFIs and improved survival in haematological malignancy patients.
Methods: A Systematic Review that followed PRISMA guidelines, was completed using randomized controlled trials, cohort studies and observational studies that evaluated antifungal prophylaxis in acute leukemia and associated haematologic malignancies. The extracted data included the type of antifungal agent(s) used; the number of proven/probable IFIs; the number of breakthrough infections; overall survival; adverse events and treatment discontinuation. Since there was considerable heterogeneity among study design and outcome measures, findings were synthesized narratively.
Results: Posaconazole consistently demonstrated greater efficacy than both Fluconazole and Itraconazole for the prevention of IFIs, specifically invasive mold infections with a significant reduction in invasive aspergillosis. A number of studies demonstrated that patients receiving Posaconazole experienced improved overall survival, fewer breakthrough infections and less use of empirical antifungal therapy. Echinocandins, most notably Micafungin, were well-tolerated and demonstrated efficacy in certain clinical scenarios. Voriconazole continued to be a viable option; however, due to toxicity and pharmacokinetic variability, it was often discontinued. Fluconazole was effective in preventing candida infections; however, it offered limited coverage for mold infections. Newer formulations of Posaconazole resulted in enhanced drug exposure and clinical usefulness.
Conclusion: The current evidence suggests that Posaconazole is a very effective prophylactic antifungal agent for high-risk patients with acute leukemia. It has broad-spectrum activity, predictable pharmacokinetics and demonstrates efficacy against invasive mold infections making it the first-line option for these patients; however, alternatives will need to be available for azole-intolerant patients. Multicenter studies will be required to define optimal patient selection criteria and monitor antifungal resistance.
