micafungin and Zygomycosis

Micafungin is a echinocandin. It inhibits beta-1,3-D-glucan synthesis, thus achieving fungicidal activity against virtually all Candida spp., including those resistant to fluconazole, and fungistatic activity against Aspergillus spp., as well as several but not all pathogenic molds. Results from in vitro studies, animal models, small clinical trials, hint at possible future indications such as invasive aspergillosis and empirical viantifungal therapy, although currently there is little information published.. To describe published data of micafungin as treatment against invasive mold infections, specially analysing its role in the inmunodepressed host and critical care setting.. A systematic review of literature using the principal medical search engines was performed. Terms such as micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy were crossed. Febrile neutropenia patients were excluded.. Several studies in these setting were identified and were described in this review. Although there were no blinded randomized clinical trials published, treatment or prophylaxis of invasive aspergillosis and other invasive mould infections with micafungin described in open clinical studies were analyzed.. Micafungin could play a future important role as a primary or rescue therapy, alone or in combination, in the treatment or prophylaxis of invasive fungal infections caused by moulds. New randomized clinical trials are needed to confirm their efficacy.

Topics: Adult; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Child; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation, Preclinical; Echinocandins; Fluconazole; Forecasting; Fungemia; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lipopeptides; Micafungin; Multicenter Studies as Topic; Mycoses; Organ Transplantation; Postoperative Complications; Premedication; Prospective Studies; Randomized Controlled Trials as Topic; Zygomycosis

A 67-year-old man was diagnosed with multiple myeloma IgA-lambda type, Durie-Salmon classification stage IIIA in October 2001. He received five courses of induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone and then underwent high dose chemotherapy followed by autologous stem cell transplantation in March 2003. He achieved partial response, but then relapsed after treatment with thalidomide and was admitted to our hospital in June 2007. The patient was complicated by tumor lysis syndrome (TLS) after receiving bortezomib therapy twice. Computed tomography after bortezomib therapy showed the rapid appearance of tumors in the right upper lobe of the lung, tail of the pancreas and the spleen. Though he was treated with antifungal agents, micafungin and voriconazole, he died eighty-five days after admission. Autopsy specimen showed fungal clumps and hemorrhagic infarction in the lung and spleen, and vegetation at the mitral valve was the same fungus as found in the lung. We diagnosed disseminated zygomycosis based on the pathological fungal morphology. This case suggested that metabolic acidosis was caused by TLS, while poorly controlled diabetes, secondary hemochromatosis due to transfusion, and breakthrough zygomycosis during antifungal therapy were thought to be factors contributing to the development of zygomycosis.

Topics: Acidosis; Aged; Antifungal Agents; Antineoplastic Agents; Boronic Acids; Bortezomib; Echinocandins; Fatal Outcome; Humans; Lipopeptides; Male; Micafungin; Multiple Myeloma; Pyrazines; Pyrimidines; Triazoles; Tumor Lysis Syndrome; Voriconazole; Zygomycosis

A 69-year-old man, who had been receiving prednisolone for 11 months for treatment of interstitial pneumonia, was diagnosed with acute myeloid leukemia. During induction therapy, he developed severe pneumonia. Although meropenem and micafungin were started, he died of circulatory failure owing to massive gastrointestinal bleeding. Autopsy specimens obtained from the stomach revealed fungal hyphae, which had invaded diffusely into submucosal vessels and caused the massive gastric bleeding. The same hyphae were also observed in both lungs. A diagnosis of disseminated zygomycosis was confirmed by its characteristic histopathological findings. Because zygomycetes are spontaneously resistant to the newer antifungal agents, such as voriconazole or micafungin, it seems likely that the prevalence of zygomycosis as a breakthrough infection may increase in the future. Zygomycosis is a rare, but life-threatening, deep fungal infection that appears in immunologically or metabolically compromised hosts. Its manifestations are clinically similar to those of invasive aspergillosis. In addition to the well-established epidemiology of zygomycosis, this case suggests the following new characteristics. (1) Although the gastrointestinal manifestation of zygomycosis is relatively rare, it is observed more frequently than invasive aspergillosis. (2) Gastrointestinal zygomycosis occasionally leads to the development of necrotic ulcers and may induce hemorrhagic shock.(3) We should be cautious of an occurrence of breakthrough zygomycosis when we use echinocandins for patients with known risk factors, especially steroid use and neutropenia. (4) For patients who are receiving broad-spectrum antibiotics and echinocandins, who are negative for culture studies and aspergillus antigen, and who present with unresolved fever, it is important to make a prompt clinical diagnosis of zygomycosis.

Topics: Aged; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Echinocandins; Fatal Outcome; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Stomach; Zygomycosis