Echinocandines and Historical Reserves

Mechanism

💊 Generic and Commercial Names

Echinocandins: Anidulafungin (Ecalta), Caspofungin (Cancida). Polyenes: Liposomal Amphotericin B (Ambisome).

🔬 Pharmacological Group

Echinocandins (semi-synthetic cyclic lipopeptides) and last-line systemic fungicide polyenes.

Mechanism of Action

Its selectivity is based on the disruption of fungal cellular structural targets:

• Inhibition of the 1,3-beta-D-glucan Synthase Enzyme of Echinocandins: They selectively and non-competitively bind and inhibit this polymerizing catalytic enzyme (encoded by the gene FKS1), which is responsible for the synthesis of 1,3-beta-D-glucan (dural structural component of the fungal cell wall that provides rigidity and osmotic resistance). When glucan synthesis is blocked, the loss of structural consistency of the wall is caused with rapid osmotic fungal cell lysis with a fungicidal course.
• Porogenic Effect of Amphotericin B (Polyene): It binds specifically and with high affinity to ergosterol present in the fungal cell membrane, physically interacting with various lipid molecules to form cylindrical transmembrane pores. These pores cause the rapid and uncontrolled efflux of potassium (K⁺), magnesium (Mg²⁺) and dural metabolites, breaking the electrochemical potential and inducing rapid fungal cell death.

Pharmacokinetics

Key Pharmacokinetics

Antifungal Spectrum

• Echinocandins: Excellent bactericidal activity against yeasts such as Candida spp. (including azole-resistant strains such as C. krusei and C. glabrata), and moderate bacteriostatic activity against invasive Aspergillus spp.. They have no useful activity against Cryptococcus neoformans or mucormycosis agents.
• Liposomal Amphotericin B: Total course spectrum. Excellent fungicidal spectrum against Candida spp., Aspergillus spp., agents of mucormycosis (zygomycosis), Histoplasma capsulatum and deep refractory fungal cocci.

Indicators and dose

Dosage and Adjustment

• Anidulafungin: Loading dose of 200 mg IV on day 1, followed by 100 mg every 24 hours IV as a slow infusion in 14-day treatments after resolution of blood cultures. It does not require adjustment in renal or hepatic failure.
• Caspofungin: Loading dose of 70 mg IV on day 1, followed by 50 mg every 24 hours IV as a 1-hour infusion.
• Liposomal Amphotericin B: 3 to 5 mg/kg every 24 hours IV (may be increased to 10 mg/kg in cases of CNS mucormycosis).
• Adjustment of Caspofungin in Liver Failure:
  • In moderate hepatic impairment (Child-Pugh B), reduce the daily maintenance dose of Caspofungin to 35 mg every 24 hours after the loading dose.

Security

Contraindications and ADRs

• Contraindications: Allergy to echinocandins; severe decompensated liver failure (for Caspofungin); history of extreme nephrotoxicity from amphotericin.
• Adverse Effects (ADR):
  • Excellent Safety Profile of Anidulafungin: It does not require phase I enzymatic renal or hepatic clearance, making it the safest systemic antifungal in routine clinical practice in critically ill patients with active multiple organ failure.
  • Amphotericin B nephrotoxicity with a common course: Acute renal tubular necrosis and severe vasoconstriction of the renal afferent arteriole, inducing local ischemia and cellular damage. It is manifested by a rapid decline in the glomerular filtration rate, type I renal tubular acidosis, and extreme hypokalemia that requires daily potassium and magnesium replacement. The liposomal formulation significantly reduces this risk by selectively targeting the drug to macrophages and avoiding direct contact with cells of the proximal renal tubule.