Antimicrobials · Antifungals
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Amphotericin B binds to ergosterol in the fungal cell membrane, creating pores that cause leakage of intracellular ions and cell death.
The most significant dose-limiting side effect of Amphotericin B is nephrotoxicity, characterized by renal vasoconstriction and direct tubular injury.
Amphotericin B causes distal renal tubular acidosis (Type 1 RTA), leading to hypokalemia and hypomagnesemia due to increased membrane permeability.
Patients receiving Amphotericin B frequently experience infusion-related reactions, including fever, chills, rigors, and hypotension, often referred to as shake and bake.
Liposomal formulations of Amphotericin B are preferred to reduce the incidence of nephrotoxicity and infusion-related reactions compared to conventional deoxycholate formulations.
Amphotericin B is the gold standard induction therapy for severe cryptococcal meningitis and mucormycosis.
Pre-treatment with intravenous saline hydration is mandatory to mitigate the risk of acute kidney injury associated with Amphotericin B administration.
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A 54-year-old man with poorly controlled diabetes mellitus presents with a 3-day history of facial pain, nasal congestion, and a black eschar on his nasal turbinate. Physical examination reveals proptosis and cranial nerve palsies. A biopsy of the nasal tissue shows broad, non-septate hyphae with wide-angle branching. The patient is started on an intravenous antifungal agent. Two days later, his serum creatinine increases from 0.9 mg/dL to 1.8 mg/dL, and he develops hypokalemia.
Which mechanism is responsible for the patient's electrolyte abnormalities?
Increased distal tubular membrane permeability
The patient has mucormycosis treated with Amphotericin B, which causes Type 1 RTA and electrolyte wasting by forming pores in the renal tubular cell membranes.
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Classification
Polyene antifungal; the gold standard for severe systemic fungal infections.
Indications
Cryptococcal meningitis, mucormycosis, and disseminated histoplasmosis.
Mechanism of Action
Binds ergosterol in fungal cell membranes, forming pores leading to cell death.
Side Effects
Nephrotoxicity, infusion-related reactions, and hypokalemia.
Contraindications / Monitoring
Renal failure; monitor serum creatinine, potassium, and magnesium.
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Mechanism of Action
Amphotericin B binds irreversibly to ergosterol within the fungal cell membrane. This interaction creates transmembrane ion channels (pores) that disrupt membrane permeability. The resulting leakage of intracellular potassium and other small molecules leads to rapid fungicidal activity.
Unique Properties
Known colloquially as Amphoterrible due to its severe toxicity profile. It possesses the broadest spectrum of activity among all antifungals, making it the drug of choice for life-threatening invasive fungal infections.
Indications
Indicated for induction therapy in cryptococcal meningitis (often with flucytosine) and invasive aspergillosis. It is the primary treatment for mucormycosis and severe coccidioidomycosis. Used for empiric therapy in patients with persistent febrile neutropenia.
Pharmacokinetics
Poorly absorbed orally; must be administered intravenously. It is highly protein-bound and distributes widely into tissues, though penetration into the cerebrospinal fluid is poor. Excretion is slow, primarily non-renal, but it causes significant nephrotoxicity.
Side Effects & Adverse Events
Patients frequently experience infusion-related reactions including fever, chills, and rigors, often managed with premedication. Nephrotoxicity is the dose-limiting factor, caused by renal vasoconstriction and direct tubular injury. Patients often develop hypokalemia and hypomagnesemia due to distal tubular wasting.
Contraindications
Hypersensitivity to the drug is an absolute contraindication. Use with extreme caution in patients with pre-existing renal impairment, as the drug can precipitate acute tubular necrosis. Avoid concurrent use with other nephrotoxic agents like aminoglycosides.
Monitoring
Baseline and serial serum creatinine and BUN are mandatory to assess renal function. Monitor serum potassium and magnesium levels closely, as replacement is frequently required. Perform a complete blood count to monitor for potential anemia.
Clinical Pearls
Always distinguish between the conventional formulation and liposomal preparations, which have a significantly lower risk of nephrotoxicity. If a patient develops rigors during infusion, consider the shake and bake syndrome. Remember that it is the gold standard for mucormycosis.