Amphotericin B Spectrum of Activity
Amphotericin B is a broad-spectrum polyene antifungal agent with activity against most clinically relevant yeasts and molds, including Candida species, Aspergillus species, Cryptococcus neoformans, endemic fungi (Histoplasma, Blastomyces, Coccidioides), Mucorales (Mucor, Rhizopus, Absidia), and Sporothrix schenckii, but lacks activity against bacteria, viruses, and certain resistant fungi like Scedosporium prolificans and many Fusarium species. 1, 2
Mechanism of Action
- Amphotericin B binds to ergosterol in fungal cell membranes, creating pores that disrupt membrane permeability and cause leakage of intracellular components (potassium, magnesium), ultimately leading to cell death 1, 2, 3
- The drug is fungicidal or fungistatic depending on concentration achieved in body fluids and fungal susceptibility 2
Spectrum Coverage
Yeasts with Excellent Activity
- Candida albicans (generally highly susceptible, MIC 0.03-1.0 mcg/mL) 2, 3
- Cryptococcus neoformans (MIC 0.03-1.0 mcg/mL) 2, 3, 4
- Candida tropicalis, C. parapsilosis (though some strains may develop resistance during treatment) 3
Molds with Excellent Activity
- Aspergillus fumigatus and other Aspergillus species (MIC 0.03-1.0 mcg/mL) 1, 2, 3
- Mucorales including Mucor mucedo, Rhizopus, Absidia, and related genera (Conidiobolus, Basidiobolus) 2, 3
- Histoplasma capsulatum 2, 3
- Blastomyces dermatitidis 2, 3
- Coccidioides immitis 2, 3
- Sporothrix schenckii (extracutaneous sporotrichosis, though some isolates show primary resistance) 2, 3
Limited or Variable Activity
- Non-albicans Candida species may be less susceptible than C. albicans 2
- Candida lusitaniae can acquire resistance during treatment 3
- Some strains of Sporothrix schenckii demonstrate primary resistance 3
Resistant Organisms
- Scedosporium prolificans (all strains resistant) 3
- Pseudallescheria boydii (Scedosporium apiospermum) (often resistant, some isolates show primary resistance) 2, 3
- Fusarium species (often resistant) 2, 3
- Bacteria, rickettsiae, and viruses (no activity) 2
Clinical Indications (FDA-Approved)
Amphotericin B is specifically indicated for progressive, potentially life-threatening fungal infections including 2:
- Aspergillosis
- Cryptococcosis (torulosis)
- North American blastomycosis
- Systemic candidiasis
- Coccidioidomycosis
- Histoplasmosis
- Zygomycosis (mucormycosis)
- Sporotrichosis
- American mucocutaneous leishmaniasis (not first-line)
Resistance Patterns
- Resistance (MIC >2 mg/L) is uncommon and emerges slowly during treatment 3
- Resistance is species-dependent and associated with alterations in membrane sterol composition 3, 4
- Treatment failure due to resistance tends to occur in patients receiving cytotoxic drugs 4
Important Clinical Considerations
Formulation Selection
- Lipid formulations (liposomal amphotericin B, amphotericin B lipid complex) are strongly preferred over conventional amphotericin B deoxycholate due to significantly reduced nephrotoxicity and infusion-related reactions 1
- Lipid formulations are particularly critical for patients at high risk for renal failure: pre-existing renal disease, hematopoietic cell transplant recipients, and those receiving concurrent nephrotoxic agents 1
Pharmacokinetic Properties
- Peak plasma concentrations range from 0.5-2 mcg/mL with standard dosing 2
- Highly protein-bound (>90%) and poorly dialyzable 2
- Prolonged elimination half-life of approximately 15 days after initial 24-hour half-life 2
- Poor CNS penetration (CSF concentrations rarely exceed 2.5% of plasma levels) 2
Common Pitfall
Do not use amphotericin B for non-invasive fungal infections such as oral thrush, vaginal candidiasis, or esophageal candidiasis in patients with normal neutrophil counts—the toxicity risk outweighs benefit 2