Table 1. First-line antifungal options for mucormycosis.
Drug | Recommended dosage | Advantages and supporting studies | Disadvantages |
---|---|---|---|
Primary antifungal therapy | |||
AmB | 1.0–1.5 mg/kg/day | >5 Decades clinical experience; inexpensive; only licensed agent for the treatment of mucormycosis | Highly toxic; poor CNS penetration |
LAmB | 5–10 mg/kg/day | Less nephrotoxic than AmB; better CNS penetration than AmB and ABLC [12]; improved outcomes vs. AmB in murine models and a retrospective clinical review [4, 13] | Expensive |
ABLC | 5–7.5 mg/kg/d | Less nephrotoxic than AmB; murine and retrospective clinical data suggest benefit of combination therapy with echinocandins [9, 14] | More nephrotoxic than LAmB [15]; possibly less efficacious than other options as monotherapy, particularly for CNS infection [9] |
Primary combination therapya | |||
Caspofungin plus lipid polyene | 70 mg iv load, then 50 mg/day for ≥2 weeks; 50 mg/m2 iv for children [16] | Favorable toxicity profile; synergistic in murine disseminated mucormycosis [14]; retrospective clinical data suggested superior outcomes with combination caspofungin-lipid polyene therapy for rhino-orbital-cerebral mucormycosis [9] | Clinical data of combination therapy are very limited |
Micafungin OR anidulafungin plus lipid polyene | 100 mg/day for ≥2 weeks; micafungin 4 mg/kg/day for children [17]; micafungin 10 mg/kg/day for low-birth weight infants [18]; anidulafungin 1.5 mg/kg/day for children [19] | Favorable toxicity profile; synergistic with LAmB in murine model of disseminated mucormycosis [20] | No clinical data |
Deferasirox plus lipid polyene | 20 mg/kg po qd for 2–4 weeks | Highly fungicidal for Mucorales in vitro [21]; synergistic with LAmB in murine model of disseminated mucormycosis [21] | Only available for enteral administration; no clinical data, although a phase II clinical trial is ongoing |
NOTE. Primary therapy should generally include a polyene. Non–polyene-based regimens may be appropriate for patients who refuse polyene therapy or for patients with mild disease in relatively immunocompetent hosts that can be surgically eradicated (e.g., isolated suprafascial cutaneous infection). ABLC, amphotericin B lipid complex; AmB, amphotericin B deoxycholate; CNS, central nervous system; iv, intravenous; LAmB, liposomal amphotericin B; po, oral; qd, once per day.
Prospective, randomized trials are necessary to confirm the suggestion of benefit of combination therapy from animal and small, retrospective human studies of mucormycosis. Also, increasing the dosage of any of the echinocandins is not recommended based on paradoxical loss of benefit of combination therapy at echinocandin dosages of ≥3 mg/kg/d.