This review compares the pharmacology, spectrum of antifungal activity, pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of the three licensed
echinocandins:
caspofungin,
micafungin and
anidulafungin.
Echinocandins inhibit the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for
fungal infections. The
echinocandins exhibit potent in vitro and in vivo fungicidal activity against Candida species, including
azole-resistant pathogens. For all agents, strains with
drug minimum inhibitory concentrations (MICs) of ≤ 2 μg/mL are considered susceptible; the MIC at which 90% of isolates tested were inhibited (MIC₉₀) values are typically <2 μg/mL but 100-fold higher MIC₉₀ values are seen with Candida parapsilosis (1-2 μg/mL) and Candida guilliermondii (1-4 μg/mL). Activity is comparable between the three agents, although limited data indicate that
anidulafungin may have low MICs against C. parapsilosis and Candida glabrata strains that demonstrate elevated MICs to
caspofungin and
micafungin. All three drugs have good fungistatic activity against Aspergillus spp., although minimal effective concentrations of
micafungin and anidulfungin are 2- to 10-fold lower than those for
caspofungin. Synergistic/additive in vitro effects of
echinocandins when combined with a polyene or
azole have been observed. Clinical resistance to the
echinocandins is rare despite case reports of
caspofungin resistance in several Candida spp. Resistance has been attributed to mutations in the FKS1 gene within two hot spot regions, leading to amino acid substitutions, mostly at position 645 (
serine), yet not all FKS1 mutants have
caspofungin MICs of >2 μg/mL. Of the three
echinocandins, the in vitro 'paradoxical effect' (increased growth at supra-MIC
drug concentrations) is observed least often with
anidulafungin. All
echinocandins have low oral bioavailability, and distribute well into tissues, but poorly into the CNS and eye.
Anidulafungin is unique in that it undergoes elimination by chemical degradation in bile rather than via hepatic metabolism, has a lower maximum concentration and smaller steady state under the concentration-time curve but longer half-life than
caspofungin or
micafungin. In children, dosing should be based on body surface area. Daily doses of
caspofungin (but not
micafungin and
anidulafungin) should be decreased (from 50 to 35 mg) in moderate
liver insufficiency. All
echinocandins display concentration-dependent fungicidal (for Candida) or fungistatic (for Aspergillus) activity. The postantifungal effect is 0.9-20 hours against Candida and <0.5 hours against Aspergillus. The
echinocandins are well tolerated with few serious
drug-drug interactions since they are not appreciable substrates, inhibitors or inducers of the
cytochrome P450 or
P-glycoprotein systems. In parallel with the greater clinical experience with
caspofungin, this agent has a slightly higher potential for adverse effects/
drug-drug interactions, with the least potential observed for
anidulafungin.
Caspofungin (but not
micafungin or
anidulafungin) dosing should be increased if coadministered with
rifampicin and there are modest interactions of
caspofungin with
calcineurin inhibitors. All three agents are approved for the treatment of oesophageal
candidiasis, candidaemia and other select forms of
invasive candidiasis. Only
micafungin is licensed for antifungal prophylaxis in
stem cell transplantation, whereas
caspofungin is approved for empirical
therapy of
febrile neutropenia.
Caspofungin has been evaluated in the salvage and primary
therapy of invasive
aspergillosis. Combination regimens incorporating an
echinocandin showing promise in the treatment of
aspergillosis. However,
echinocandins remain expensive to use.