title: Successful treatment of pulmonary blastomycosis with continuously infused amphotericin B deoxycholate after failure with liposomal amphotericin B.
abstract: OBJECTIVE
  To describe a case of successful treatment of severe pulmonary blastomycosis with amphotericin B deoxycholate after failure of liposomal amphotericin B.
  
  
  METHODS
  A 35-year-old male was exposed to damp decomposing wood while cleaning his basement. He subsequently developed a cough, malaise, fever, nausea, vomiting, and diarrhea. He was admitted to the hospital and intubated for worsening pulmonary symptoms. Microscopic examination of his sputum indicated Blastomyces dermatitidis. Liposomal amphotericin B was administered for 6 days, but the patient's temperature reached 39.6 °C and his white blood cell (WBC) count reached 52,300/μL. Extensive consolidation of both lungs fields was observed on chest X-ray. Because of progressive clinical deterioration, the treatment was switched to amphotericin B deoxycholate by continuous infusion. That change resulted in clinical improvement, with abrupt reductions (within 48 hours) in temperature and the WBC count. By day 14 of therapy (day 8 of amphotericin B deoxycholate), the chest X-ray showed improvement in diffuse airspace filling. After 16 days of amphotericin B treatment, intravenous followed by oral voriconazole was administered for 3 months. Eight months later the patient's strength had improved significantly, but he still had occasional episodes of shortness of breath.
  
  
  CONCLUSIONS
  The management of blastomycosis is challenging because of the lack of clinically supporting data. The gold standard for severe pulmonary blastomycosis had been amphotericin B deoxycholate; however, improved safety data with liposomal amphotericin B for other fungal infections has suggested this as an effective alternative. This report describes a patient with severe pulmonary blastomycosis failing 6 days of liposomal amphotericin B, yet he tolerated and clinically responded to continuous infusion of amphotericin B deoxycholate. Based on this case report and a simulated pharmacokinetic/pharmaco dynamic analysis, continuous infusion of amphotericin B deoxycholate may be a reasonable option for enhanced efficacy and minimal toxicity in patients with blastomycosis.
  
  
  CONCLUSIONS
  Ours is the first case report to use continuous infusion of amphotericin B deoxycholate for the management of pulmonary blastomycosis. These results suggest that liposomal amphotericin B may not be adequate in some patients for the management of B. dermatitidis pulmonary infections.
authors.affiliation: Department of Pharmacy, St. Boniface General Hospital, Winnipeg, Manitoba, Canada. rariano@sbgh.mb.ca
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ariano
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Mitchelmore
authors.forename: Philippe Rs
authors.initials: PR
authors.lastname: Lagacé-Wiens
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Zelenitsky
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D001759:Blastomycosis / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B