Background: Invasive fungal infections, particularly those due to moulds, remain one of the most difficult challenges in the care of patients with hematologic malignancies. The most common non-Aspergillus mould infections are due to Fusarium spp. These infections do not always respond to Amphotericin B or the lipid formulations of Amphotericin B when used alone, even though in vitro susceptibility might suggest otherwise. Combination anti-fungal therapy with potentially synergistic agents targeting the fungal cell wall and cell membrane are being investigated with great interest. We report a case of disseminated Fusarium proliferatum involving the lungs, liver and spleen treated with a combination of an echinocandin, caspofungin, and amphotericin B lipid complex in a patient with acute myeloid leukaemia (AML). Case Report: A 72-year-old male retired gardener was referred to the Leukaemia Service November 9 th , 2001 with a two-week history of fatigability, malaise, and pancytopaenia A bone marrow biopsy and peripheral blood confirmed a diagnosis of AML. Although the patient was a chest x-ray identified a left upper lobe consolidation, which was treated as a community acquired pneumonia syndrome with oral levofloxacin, 500 mg daily followed by defervescence. The patient developed a febrile neutropenic episode on day 9 of remission-induction, the investigations of which revealed no positive cultures and an unchanged chest x-ray appearance. The patient failed to defervesce after five days of empirical intravenous piperacillin/tazoactam and a follow up chest x-ray showed progression of the left upper lobe consolidation. A computerized tomographic (CT) examination of the chest showed wedge shaped pleural based opacities. A bronchoalveolar lavage was performed and intravenous amphotericin B deoxycholate (dAmB), 1 mg/kg/day was administered. The microbiological culture of the washings grew Fusarium proliferatum. CT’s of the abdomen and chest performed after 10 days of dAmB therapy demonstrated lesions consistent with hepatosplenic fungal disease and progression of the pleural-based nodular opacities, respectively. ABLC, 5 mg/kg/day, substituted for dAmB due to nephrotoxicity, together with Caspofungin, 70mg IV on day 1 then 50mg IV daily, were administered for progressive disseminated fusariosis. The patient subsequently achieved a complete haematological remission and underwent consolidation therapy while receiving this combination therapy. Follow up CT examinations of the thorax and the abdomen performed just prior to commencing consolidation therapy demonstrated partial resolution of the pulmonary nodules without significant improvement in the hepatosplenic lesions. The patient, in remission, was discharged home, to continue combination therapy. Repeat CT studies of thorax and abdomen performed after 64 days of combination therapy demonstrated resolution of pulmonary nodules and healing of the lesions in the liver and spleen.He remained on this treatment until he had completed a total of 90 days of therapy. The patient did not receive any further antifungals for 3 months at which time a relapse of his AML was documented. The patient died following a failed attempt at a second remission-induction. A post-mortem exam was not performed. Conclusion: This case report suggests a therapeutic effect of a combination of caspofungin and ABLC for the treatment of disseminated fusariosis progressing while receiving dAmB. If further similar observations can be documented then carefully designed controlled trials assessing the safety and efficacy of combination caspofungin/ABLC anti-fungal therapy may be warranted.
Full conference title:
The 15 th Congress of the International Society for Human and Animal Mycology
- ISHAM 15th (2003)