amphotericin

Amphotericin B is a polyene antifungal antibiotic produced by Streptomyces nodosus. It is used systemically for serious fungal infections and remains a standard induction therapy for several invasive mycoses. It binds to ergosterol in fungal cell membranes, forming pores that increase membrane permeability and cause leakage of ions and other cellular contents, leading to fungal cell death. Its affinity for ergosterol is greater than for cholesterol, but it can also interact with human membranes, accounting for notable toxicity.

Clinical spectrum includes cryptococcal meningitis, disseminated histoplasmosis, blastomycosis, coccidioidomycosis, mucormycosis, aspergillosis, and severe candidiasis; it is fungicidal against many susceptible fungi. Because of toxicity, it is increasingly used in lipid formulations (liposomal amphotericin B, amphotericin B lipid complex, or colloidal dispersion) that reduce nephrotoxicity while permitting higher dosing; conventional amphotericin B deoxycholate remains in use where resources are limited.

Administration is intravenous; CNS penetration is limited, making CNS infections primarily treated with high-dose therapy or intrathecal administration in specialized settings. Dosing varies by formulation; lipid formulations typically require lower nephrotoxic risk but are more costly.

Adverse effects include nephrotoxicity (often reversible), electrolyte disturbances such as hypokalemia and hypomagnesemia, and infusion-related reactions (fever, chills, rigors, hypotension). Pretreatment with antipyretics or steroids and slower infusion rates may mitigate reactions; hydration mitigates nephrotoxicity. Lipid formulations reduce but do not eliminate toxicity. Concomitant use with other nephrotoxic drugs should be avoided.

Resistance is uncommon but may involve alterations in ergosterol content or membrane composition. Amphotericin B remains a cornerstone of therapy, frequently used with flucytosine for cryptococcal meningitis and as salvage therapy for mucormycosis and other deep-seated fungal infections.