Cunninghamella bertholletiae infection in a bone marrow transplant patient: amphotericin lung penetration, MIC determinations, and review of the literature

Abstract

Infections caused by Cunninghamella bertholletiae, an opportunistic fungal organism, have an extremely high mortality rate. A fatal case of C. bertholletiae fungal pneumonia occurred in a man who had received an allogeneic bone marrow transplant. Aggressive debridement and high-dose liposomal amphotericin B failed to eradicate the infection. Right lung tissue samples obtained during lobectomy were assayed for amphotericin B concentrations by high-performance liquid chromatography, and minimum inhibitory concentration (MIC) determinations of amphotericin B against C. bertholletiae were determined by the macrobroth dilution method. The MIC for the isolate of C. bertholletiae was 4 microg/ml. Amphotericin B lung concentrations averaged 9.5 microg/ml (range 3.7-13.8 microg/ml), with a corresponding serum trough concentration of 0.9 microg/ml. To our knowledge, this is the first reported case of amphotericin B concentrations measured at the site of infection in a patient with a pulmonary Cunninghamella infection, together with a corresponding MIC of the organism. The patient's death, which occurred despite aggressive debridement and high amphotericin B lung concentrations, highlights the need for novel strategies to treat infections caused by invasive molds such as C. bertholletiae.