LAUSR

ANTIFUNGAL COMBINATIONS IN MUCORMYCOSIS Brigmon and colleagues reported the safety of long-term isavuconazole in a poorly controlled diabetic with rhinocerebral mucormycosis. The authors diagnosed rhino-orbital mucormycosis and managed it with several antifungals, including liposomal amphotericin-B, intravenous micafungin, posaconazole, and finally isavuconazole. The index patient could have benefited from early surgery (partial or complete) since the drug penetration in the necrotic tissues (due to angioinvasion and thrombosis) is poor. Understandably, in the absence of surgical intervention, adding multiple antifungal agents failed to improve clinical status by day 11 of therapy. Existing knowledge and current recommendations suggest surgery as the primary treatment for all forms of mucormycosis, including rhino-orbital and pulmonary mucormycosis. The evidence for the combination of caspofungin with liposomal amphotericin is based on a retrospective study conducted over 12 years, comparing six patients receiving the combination therapy with 34 patients on monotherapy. Further, the effect of caspofungin on the murine model of mucormycosis was demonstrated for Rhizopus orzyae (also known as R. arrhizus). Mucorales are intrinsically resistant to echinocandins, except for Rhizopus oryzae, which has the FKS gene encoding for 1,3b-glucan synthase (the target for echinocandins). Whether Rhizopus microsporus (current case) would respond to a combination of caspofungin and liposomal amphotericin remains unknown. While it is reassuring to note the safety of isavuconazole, there is no randomized trial evaluating the drug in mucormycosis, and the potential for QTc shortening needs to be remembered. The optimal duration of therapy is unknown, and the favorable response seen in the current case can be attributable to the control of diabetes mellitus. The role of optimizing blood sugars cannot be undermined, as mucormycosis has been shown to resolve spontaneously following diabetes control. Thus, controlling the underlying medical condition and combined medical-surgical therapy are the cornerstone in managing mucormycosis.