colistin and Mucormycosis

Mucormycosis is an opportunistic, life-threatening fungal infection caused by fungi of the class Zygomycetes. The disease has traditionally been reported in immunocompromised patients, premature infants, diabetics, transplant recipients, prolonged use of corticosteroids or in condition associated with increased availability of serum iron such as acidosis or deferoxamine administration. The infection is progressive and associated with a high mortality unless treatment is initiated promptly. The number of cases of gastrointestinal mucormycosis indexed on PubMed over the past 2 decades has shown an alarming rise. Moreover, the infection is being increasingly reported in patients without the traditional risk factors. We report successful management of an immunocompetent child with gastrointestinal mucormycosis who responded to aggressive treatment with surgical debridement and antifungal agents. The fungicidal activity of colistin (polymyxin E) has also been highlighted.

Topics: Antifungal Agents; Child; Colistin; Debridement; Gastrointestinal Diseases; Histocytochemistry; Humans; Male; Microscopy; Mucormycosis; Treatment Outcome

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.

Topics: Adenosine Triphosphate; Animals; Antifungal Agents; Colistin; Cytoplasm; Female; Hyphae; Lung; Lung Diseases, Fungal; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Mucorales; Mucormycosis; Rhizopus; Spores, Fungal; Tetrazolium Salts; Vacuoles