Eradication of invasive mucormycosis--effectiveness of the Echinocandin FK463.
BACKGROUND
Invasive rhinocerebral mucormycosis is a rare and often fatal opportunistic fungal infection. It is encountered in immunocompromised hosts exemplified by those with diabetes, human immunodeficiency viruses and particularly haematologic malignancies typically after high-dose chemotherapy and stem cell transplantation. In contrast to the more usual outcome with rapid progression and death. We now describe a successful eradication attributable to the use of a newly available antifungal agent.


METHODS
Haematology department and bone marrow transplantation unit.


METHODS
Two patients are contrasted. The first with acute leukaemia developed rapidly progressive facial swelling with mucormycosis proven on biopsy. Treatment over 2 months with maximally tolerated doses of amphotericin failed to halt intracranial extension and death resulted. The second, presented with acute lymphoblastic leukaemia in August 1997, underwent successful autologous bone marrow transplantation in February 1998. Relapse followed in March 1999 and after reinduction and consolidation receive a matched unrelated volunteer allograft in September 1999. A second recurrence was documented in April 2000 and in spite of achieving remission he developed a fever that was managed empirically with intravenous amphotericin and, on discharge, oral itraconazole. Left-sided facial swelling expanded rapidly and biopsy showed extensive invasion of the maxillary sinus with mucormycosis. FK463 was added on 5 June 2000 with gradual reduction in facial pain and within 1 month all clinical signs and resolved. Serial biopsies that included histopathologic investigation and microbiologic cultures confirmed eradication of the invasive mucor. In view of the potential danger of recrudescence this treatment regimen was continued through further chemotherapy and, once again disease-free, a second matched unrelated volunteer allograft took place in August 2000. Full reassessment at the time failed to demonstration any residual fungus. Engraftment was confirmed but neutropenic sepsis resulted in severe inflammatory response syndrome with progression to multiple organ dysfunction to which he succumbed without any evidence of leukaemic or systemic mycosis.


CONCLUSIONS
Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.
Jacobs
Peter
P
The Department of Haematology and Bone Marrow Transplant Unit Incorporation the Searll Research Laboratory for Cellular and Molecular Biology, Costantiaberg Medi-Clinic, Burnham Road, Plumstead, Cape Town, 7800, South Africa. haematol@icon.co.za
Wood
Lucille
L
Du Toit
Andrew
A
Esterhuizen
Ken
K
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D054714:Echinocandins; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D017964:Itraconazole / Q000627:therapeutic use; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy / Q000601:surgery; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use*; D008297:Male; D000077551:Micafungin; D009091:Mucormycosis / Q000188:drug therapy* / Q000209:etiology; D009102:Multiple Organ Failure / Q000209:etiology; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010508:Periodontal Abscess / Q000150:complications / Q000382:microbiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications; D012852:Sinusitis / Q000150:complications / Q000382:microbiology; D013156:Splenectomy; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D014184:Transplantation, Homologous
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D017964:Itraconazole; D000666:Amphotericin B; D000077551:Micafungin