AAC Accepts, published online ahead of print on 26 October 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Ben-Ami, R. Articles by Kontoyiannis, D. P. PubMed PubMed Citation Articles by Ben-Ami, R. Articles by Kontoyiannis, D. P.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.00956-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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, and Dimitrios P. Kontoyiannis^*

Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; College of Pharmacy, University of Houston, Houston, Texas; Department of Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

^* To whom correspondence should be addressed. Email: dkontoyi{at}mdanderson.org.

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 Rhyzopus oryzae infection. Colistin exhibited fungicidal activity in vitro against Mucorales spores and mycelia. At the colistin minimum inhibitory concentration, 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 leakage of intracellular contents. 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.