title: 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.
authors.affiliation: Department of Pharmacy, College of Pharmacy, University of Illinois at Chicago, 60612-7320, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Garey
authors.forename: S L
authors.initials: SL
authors.lastname: Pendland
authors.forename: V T
authors.initials: VT
authors.lastname: Huynh
authors.forename: T H
authors.initials: TH
authors.lastname: Bunch
authors.forename: G M
authors.initials: GM
authors.lastname: Jensen
authors.forename: K J
authors.initials: KJ
authors.lastname: Pursell
mesh_terms: D000666:Amphotericin B / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D020093:Cunninghamella / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009091:Mucormycosis / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B