Chapter 37  ·  Module 4
Echinocandins
Caspofungin, Micafungin, and Anidulafungin — mechanism, spectrum, resistance, and clinical positioning
GS = glucan synthase  ·  IV = intravenous  ·  AUC = area under the concentration-time curve  ·  MIC = minimum inhibitory concentration  ·  CYP = cytochrome P450  ·  TDM = therapeutic drug monitoring  ·  FKS = glucan synthase gene  ·  ALT = alanine aminotransferase
Mechanism of Action
Target
Beta-1,3-d-Glucan Synthase
  • Inhibits Fks subunit of glucan synthase at inner membrane leaflet
  • Blocks beta-1,3-d-glucan chain elongation
  • Cell wall destabilizes → osmotic lysis
  • Target absent from mammalian cells → excellent tolerability
Activity
Fungicidal vs. Fungistatic
  • Fungicidal: most Candida species (AUC/MIC-driven)
  • Fungistatic: Aspergillus (hyphal tip inhibition only)
  • No activity: Cryptococcus, Mucorales, Fusarium
  • No CYP metabolism → minimal drug interactions
Agent Comparison
Property Caspofungin Micafungin Anidulafungin
Elimination Chemical degradation + N-acetylation; biliary and renal Hepatic (arylsulfatase, COMT); biliary Non-enzymatic chemical degradation; biliary — no hepatic metabolism
Loading dose 70 mg on Day 1 None required 200 mg on Day 1
Maintenance dose 50 mg once daily (70 mg if above 80 kg) 100 mg once daily (candidemia) 100 mg once daily
Hepatic adjustment Reduce to 35 mg if Child-Pugh 7–9 None (mild-moderate) None (any severity)
Key interaction CYP inducers → increase to 70 mg; cyclosporine → avoid; tacrolimus → monitor TDM Sirolimus → monitor; minimal other interactions No pharmacokinetic interactions
Spectrum and Resistance
Candida Coverage
Broad, Including Resistant Species
  • C. albicans, C. glabrata, C. tropicalis, C. krusei — all covered
  • C. parapsilosis — covered but higher MICs; fluconazole preferred if susceptible
  • Candida auris — typically susceptible; drug of choice
  • Advantage over fluconazole: covers fluconazole-resistant C. glabrata and C. krusei
FKS Resistance
Hot Spot Mutations
  • Mutations in FKS1/FKS2 hot spot regions reduce drug binding
  • C. glabrata: highest risk — 5–13% resistance in some centers
  • Suspect if: breakthrough candidemia on echinocandin, prior prolonged exposure
  • Cross-resistance within class → switch to liposomal amphotericin B
Clinical Positioning
First-Line Candidemia
Preferred Over Fluconazole
  • IDSA 2016 guidelines: echinocandin preferred for most candidemia
  • Superior fungicidal activity; covers resistant species empirically
  • Duration: 14 days from last positive blood culture
  • Remove intravascular catheter promptly
Step-Down to Fluconazole
When Criteria Are Met
  • Clinical improvement + hemodynamic stability
  • Blood cultures documented negative
  • Species confirmed fluconazole-susceptible
  • Neutropenia resolved; tolerating oral medications
  • No step-down for C. glabrata or C. krusei
Agent Selection Rule — Special Populations

Hepatic impairment: anidulafungin or micafungin (no dose adjustment needed). Transplant patients on cyclosporine: avoid caspofungin (ALT elevation risk) — use micafungin or anidulafungin. Rifampin co-administration: increase caspofungin to 70 mg, or use micafungin or anidulafungin. ICU polypharmacy or multiorgan dysfunction: anidulafungin preferred — no interactions, no organ-based adjustments.