title: Combination therapy for mucormycosis: why, what, and how?
abstract: The high mortality rate of mucormycosis with currently available monotherapy, particularly in hematology patients, has stimulated interest in studying novel combinations of antifungal agents to determine whether superior outcomes might be achieved. Combination lipid polyene-echinocandin therapy is the most promising of such regimens based on safety profile, the availability of parenteral formulations of echinocandins, their synergy in murine models of mucormycosis, and observational clinical data that are concordant. Other options include combination lipid polyene plus deferasirox or posaconazole therapy. Definitive, randomized, placebo-controlled phase III clinical trials are needed to determine whether combination therapy with any of these options is superior to monotherapy. Until such studies are conducted, clinicians will continue to be placed in the unacceptable position of not knowing if and when to administer combination therapy. Such a state of confusion may lead to undertreatment if combination therapy is indeed superior but is not used and, conversely, may lead to unacceptable toxicity and cost to patients if combination therapy is not superior but is used. It is critical that sponsors step forward with funding to conduct these clinical trials to determine whether outcomes from these devastating infections can be improved.
authors.affiliation: Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, University of California at Los Angeles, 1124 West Carson St., Torrance, CA 90502, USA. bspellberg@labiomed.org
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Ashraf
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.forename: Russel E
authors.initials: RE
authors.lastname: Lewis
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: George
authors.initials: G
authors.lastname: Petrikkos
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077588:Deferasirox; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D009091:Mucormycosis / Q000188:drug therapy* / Q000382:microbiology; D011090:Polyenes / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D001565:Benzoates; D054714:Echinocandins; D008055:Lipids; D011090:Polyenes; D014230:Triazoles; C101425:posaconazole; D000077588:Deferasirox