Combination Therapy for Mucormycosis: Why, What, and How?

 

 

Combination Therapy for Mucormycosis: Why, What, and How?

 

  1. Brad Spellberg1,2,
  2. Ashraf Ibrahim2,3,
  3. Emmanuel Roilides7,
  4. Russel E. Lewis4,5,
  5. Olivier Lortholary9,10,
  6. George Petrikkos8,
  7. Dimitrios P. Kontoyiannis5, and
  8. Thomas J. Walsh6

+ Author Affiliations


  1. 1Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center

  2. 2David Geffen School of Medicine at UCLA

  3. 3Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

  4. 4University of Houston College of Pharmacy

  5. 5The University of Texas MD Anderson Cancer Center, Houston

  6. 6Transplantation-Oncology Infectious Diseases Program, Cornell University and New York Presbyterian Hospital

  7. 7Third Department of Pediatrics, Aristotle University, Hippokration Hospital, Thessaloniki

  8. 8Kapodistriakon University of Athens, Greece

  9. 9Université Paris Descartes, Hôpital Necker-Enfants Malades, Service des Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker Pasteur

  10. 10Institut Pasteur, Centre National de Référence Mycologie et Antinfongiques, Unité de Mycologie Moléculaire, Centre National de la Recherche Scientifique URA3012, Paris, France
  1. Correspondence: Brad Spellberg, MD, LA BioMed, Liu Vaccine Center, 1124 West Carson St, Torrance, CA 90502 (bspellberg@labiomed.org).

 

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.

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