Combination Polyene‐Caspofungin Treatment of Rhino‐Orbital‐Cerebral Mucormycosis

Abstract

It has been axiomatic that echinocandins (e.g., caspofungin) are ineffective against mucormycosis. However, on the basis of preclinical data, we recently began treating rhino-orbital-cerebral mucormycosis (ROCM) with combination polyene-caspofungin therapy. To determine the impact of polyene-caspofungin therapy, ROCM cases identified by an International Classification of Diseases, Ninth Revision search were retrospectively reviewed to gather data on demographic characteristics, clinical history, and outcomes. The predefined primary end point was success (i.e., the patients was alive and not in hospice care) at 30 days after hospital discharge. Forty-one patients with biopsy-proven ROCM were identified over 12 years; 23 (56%) of these patients were Hispanic, and 34 (83%) were diabetic. Patients treated with polyene-caspofungin therapy (6 evaluable patients) had superior success (100% vs. 45%; Pp.02) and Kaplan-Meier survival time (Pp.02), compared with patients treated with polyene monotherapy. Patients treated with amphotericin B lipid complex had inferior success (37% vs. 72%; Pp.03) and a higher clinical failure rate (45% vs. 21%; Pp.04), compared with patients who received other polyenes. However, patients treated with amphotericin B lipid complex plus caspofungin had superior success (100% vs. 20%; Pp.009) and survival time (Pp.01), compared with patients who received amphotericin B lipid complex alone. The benefit of combination therapy, compared with monotherapy, was most pronounced in patients with cerebral involvement (success rate, 100% vs. 25%; Pp.01). In multivariate analysis, only receipt of combination therapy was significantly associated with improved outcomes (odds ratio, 10.9; 95% confidence interval, 1.3- ;Pp.02). Combination polyene-caspofungin therapy represents a promising potential alternative to polyene monotherapy for patients with ROCM. Randomized, prospective investigation of these findings is warranted.