Clinical and Economic Trade-Offs in Antifungal Therapy for Invasive Aspergillosis and Mucormycosis: A Markov Model–Based Analysis

Invasive aspergillosis and mucormycosis are life-threatening fungal infections characterized by high early mortality, substantial toxicity, and intensive healthcare resource utilization. While multiple antifungal therapies are recommended in international guidelines, their comparative clinical and economic value remains uncertain, particularly in resource-limited settings. We developed a hybrid decision tree and Markov model to evaluate antifungal strategies, including liposomal amphotericin B, isavuconazole, voriconazole, posaconazole, and caspofungin, from the perspective of the Colombian healthcare system over a 6-month horizon. Health states included clinical response, treatment failure, toxicity, and death. Outcomes included quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs), and net monetary benefit (NMB). Deterministic and probabilistic sensitivity analyses were performed. In invasive aspergillosis, isavuconazole provided a modest incremental benefit over voriconazole (+0.022 QALYs), driven primarily by improved tolerability, at an incremental cost of COP 3.4 million, yielding an ICER of COP 154.5 million/QALY. In mucormycosis, liposomal amphotericin B yielded greater survival benefits (+0.035 QALYs) but at substantially higher costs (ICER: COP 494.3 million/QALY). Across willingness-to-pay thresholds, isavuconazole and voriconazole demonstrated more favorable economic profiles, owing to lower toxicity and reduced hospitalizations. These findings highlight that the clinical–economic value of antifungal therapy is primarily determined by early survival gains, toxicity burden, and front-loaded costs. Strategies minimizing toxicity and hospitalization appear more efficient in constrained health systems, whereas survival-maximizing approaches may be justified in severe disease. This integrated analysis supports context-specific antifungal decision-making in the management of invasive fungal infections.