Antifungal activity of colistin against Mucorales species in vitro and in a murine model of Rhizopus oryzae pulmonary infection

Ronen Ben-Ami, Russell E. Lewis, Jeffrey Tarrand, Konstantinos Leventakos, Dimitrios P. Kontoyiannis

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

In immunosuppressed hosts, mucormycosis is a life-threatening infection with few treatment options. We studied the activity of colistin (polymyxin E) against Mucorales species in vitro and in a murine model of pulmonary Rhizopus oryzae infection. Colistin exhibited fungicidal activity in vitro against Mucorales spores and mycelia. At the colistin MIC, initial R. oryzae hyphal damage was followed by rapid regrowth; however, regrowth was prevented by combining colistin with a subinhibitory concentration of amphotericin B. Using electron microscopy and FM4-64 staining, we demonstrated that colistin disrupts R. oryzae cytoplasmic and vacuolar membranes, resulting in the leakage of intracellular contents. The prophylactic intranasal treatment of immunosuppressed mice with colistimethate significantly reduced the mortality rate and pulmonary fungal burden resulting from inhalational challenge with R. oryzae spores, whereas intraperitoneal colistimethate treatment had no effect. We conclude that colistin has modest in vitro and in vivo fungicidal activity against Mucorales spp. Further studies are warranted to assess the use of this drug in the prevention and treatment of mucormycosis.

Original languageEnglish (US)
Pages (from-to)484-490
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number1
DOIs
StatePublished - Jan 2010

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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