[4] Common side effects include a reaction with fever, chills, and headaches soon after the medication is given, as well as kidney problems.

Due to its extensive side effects, it is often reserved for severe infections in critically ill, or immunocompromised patients.

This is because amphotericin B resistance requires sacrifices on the part of the pathogen that make it susceptible to the host environment, and too weak to cause infection.

In the past it had been used for fungal infections of the surface of the GI tract such as thrush, but has been replaced by other antifungals such as nystatin and fluconazole.

[35] The oral lipid nanocrystal amphotericin by Matinas Biopharma is furthest along having completed a successful phase 2 clinical trial in cryptococcal meningitis.

[37][38] Very often, it causes a serious reaction soon after infusion (within 1 to 3 hours), consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness.

[39][40] The precise etiology of the reaction is unclear, although it may involve increased prostaglandin synthesis and the release of cytokines from macrophages.

This nearly universal febrile response necessitates a critical (and diagnostically difficult) professional determination as to whether the onset of high fever is a novel symptom of a fast-progressing disease, or merely the effect of the drug.

Paracetamol, pethidine, diphenhydramine, and hydrocortisone have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs is often limited by the patient's condition.

Kidney damage, including Type I (distal) renal tubular acidosis, is a frequently reported side effect, and can be severe and/or irreversible.

[45] Less kidney toxicity has been reported with liposomal formulations (such as AmBisome) and it has become preferred in patients with preexisting renal injury.

[51] Drug-drug interactions may occur when amphotericin B is coadministered with the following agents:[52] Amphotericin B binds with ergosterol, a component of fungal cell membranes, forming pores that cause rapid leakage of monovalent ions (K+, Na+, H+ and Cl−) and subsequent fungal cell death.

[53][54] It has been found that the amphotericin B/ergosterol bimolecular complex that maintains these pores is stabilized by Van der Waals interactions.

[53] The addition of free radical scavengers or antioxidants can lead to amphotericin resistance in some species, such as Scedosporium prolificans, without affecting the cell wall.

Because mammalian and fungal membranes are similar in structure and composition, this is one mechanism by which amphotericin B causes cellular toxicity.

[63] It was originally extracted from Streptomyces nodosus, a filamentous bacterium, in 1955, at the Squibb Institute for Medical Research from cultures of an undescribed streptomycete isolated from the soil collected in the Orinoco River region of Venezuela.

For decades it remained the only effective therapy for invasive fungal disease until the development of the azole antifungals in the early 1980s.

[65] Amphotericin B was used to treat a patient with disseminated coccidioidomycosis who was admitted to the U.S. Public Health Service Hospital, Seattle, Washington on January 16, 1957.

"The course was rapidly downhill with a grim prognosis as manifested by positive blood cultures, rising complement fixation titers, and failure of the skin to react to intradermal coccidioidin.

A fourteen-month follow-up following discontinuance of the drug revealed stabilization of all laboratory studies except for a re-elevation of the complement fixation titer from 1 to 16 to 1 to 32.

The lasting effect of the drug seems suggested by the patient's complete well-being after fourteen months of cessation of treatment.

The latter formulations have been developed to improve tolerability and decrease toxicity, but may show considerably different pharmacokinetic characteristics compared to conventional amphotericin B.