Non-intravenous Amphotericin B: A Review of Localized Administration Routes

BACKGROUND: Amphotericin B (AmB) remains the gold standard for treating invasive fungal infections, yet its clinical utility is frequently constrained by systemic nephrotoxicity. Localized administration routes have emerged as a sophisticated strategy to optimize the drug's therapeutic index, achieving high concentrations at the infection site while minimizing systemic exposure. This review presents the state of the art of non-intravenous (non-IV) AmB administration routes, synthesizing available evidence regarding their application as adjuvant or salvage therapies. METHODS: A comprehensive literature review was performed, integrating evidence from meta-analyses, randomized clinical trials, observational studies and case series to evaluate localized delivery protocols. RESULTS: Different nonsystemic routes are analyzed, including inhalational, intrathecal, intralesional, intraocular, intravesical, bone cement, and intraperitoneal administration. For each route, formulations, dosage protocols, and clinical applications are discussed. Furthermore, the review explores the horizon of technological innovations, specifically nanotechnology-based delivery systems (e.g., nanoparticles, thermosensitive gels), which promise to revolutionize localized therapy by overcoming current bioavailability limitations. While routes such as inhalational prophylaxis are supported by robust evidence, others remain vital salvage therapies requiring standardization. CONCLUSIONS: Non-IV administration of AmB represents a multifaceted and essential clinical tool. The transition toward localized delivery reflects a change in basic assumptions in targeted antifungal therapy, with potential that is set to expand through continuous research into optimized pharmaceutical formulations. Infographic available for this article. INFOGRAPHIC.