Cardiac toxicity of some echinocandin antifungals

Abstract

Background: Unexplained cardiovascular decompensation has been observed during central venous administration of some echinocandins.

Objective: The purpose of this study was to assess cardiac toxicity associated with the echinocandins.

Methods: Isolated rat hearts (Langendorff model) were perfused with anidulafungin (ANID), caspofungin (CASP), or micafungin (MICA) at exposures of 1, 4, and 10 times therapeutic concentrations. Changes in left ventricular contractility with experimental exposure were compared to control, and histologic and transmission electron microscopy (TEM) examinations of tissue were performed.

Results: Mean concentrations of ANID (10 – 80 µg/ml) and CASP (6 – 48 µg/ml) were associated with significant decreases in contractility (-77.1 ± 9.4% and -40.6 ± 15.6%, respectively; p < 0.05). MICA was associated with an increase in contractility (13.6 ± 2.8%, p = NS). On TEM, samples exposed to ANID and CASP had enlarged mitochondria and disintegrating myofibrils. Samples exposed to MICA showed some enlarged mitochondria.

Conclusion: Mean concentrations of ANID and CASP were associated with statistically significant decreases in left ventricular contractility at concentrations that may be achievable in humans after peripheral administration, while MICA caused no change. TEM studies suggest this may be a result of mitochondrial damage. Caution may be warranted with central administration of these agents to patients with preexisting cardiac dysfunction.

Keywords::

• anidulafungin
• cardiac function
• caspofungin
• echinocandins
• micafungin
• toxicity

Acknowledgements

The authors acknowledge Glenn Hoskins and March Ard of the University of Mississippi School of Medicine, Departments of Neurobiology and Anatomy Science for their help in the preparation and interpretation of the TEM studies.