micafungin and Acute-Disease

Micafungin (FK463) is a new lipopeptide compound (echinocandin) with activity against Aspergillus and Candida species. This study evaluated the safety and efficacy of micafungin in patients with proven or probable invasive aspergillosis (IA).. A multinational, non-comparative study was conducted to examine proven or probable (pulmonary only) Aspergillus species infection in a wide variety of patient populations. The study employed an open-label design utilizing micafungin alone or in combination with another systemic antifungal agent. Criteria for IA and therapeutic responses were judged by an independent panel.. Of the 331 patients enrolled, only 225 met diagnostic criteria for IA as determined by the independent panel and received at least one dose of micafungin. Patients included 98/225 who had undergone hematopoietic stem cell transplantation (HSCT) (88/98 allogeneic), 48 with graft versus host disease (GVHD), and 83/225 who had received chemotherapy for hematologic malignancy. A favorable response rate at the end of therapy was seen in 35.6% (80/225) of patients. Of those only treated with micafungin, favorable responses were seen in 6/12 (50%) of the primary and 9/22 (40.9%) of the salvage therapy group, with corresponding numbers in the combination treatment groups of 5/17 (29.4%) and 60/174 (34.5%) of the primary and salvage treatment groups, respectively. Of the 326 micafungin-treated patients, 183 (56.1%) died during therapy or in the 6-week follow-up phase; 107 (58.5%) deaths were attributable to IA.. Micafungin as primary or salvage therapy proved efficacious and safe in high-risk patients with IA, although patient numbers are small in the micafungin-only groups.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Drug Therapy, Combination; Echinocandins; Female; Humans; Infant; Lipopeptides; Lipoproteins; Male; Micafungin; Middle Aged; Peptides, Cyclic

Topics: Acute Disease; Adolescent; Antifungal Agents; Child; Child, Preschool; Echinocandins; Female; Humans; Immunocompromised Host; Infant; Infant, Newborn; Invasive Fungal Infections; Leukemia; Lipopeptides; Male; Micafungin; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Treatment Outcome

A 70-year-old man received a course of therapy that consisted of prednisolone, cyclosporine, and etoposide due to hemophagocytic syndrome which had developed during primary myelofibrosis. He also received micafungin (MCFG) as prophylaxis against a potential fungal infection. We diagnosed febrile neutropenia due to the hemophagocytic syndrome therapy and candidemia because Candida species were detected in blood cultures. He received liposomal amphotericin B (L-AMB) for the candidemia but did not respond to this treatment. Oliguria was diagnosed and renal failure progressed rapidly. We suspected that his renal failure had been induced by the antibiotics. We thus changed the antibiotic regimen but he died of progressive renal failure. We performed renal necropsy and diagnosed acute interstitial tubular nephritis, due to a yeast-like fungus that generally invades the renal tubules. The yeast-like fungus was later identified as Trichosporon asahii, rather than candida, by blood cultures. An immunocompromised host receiving MCFG for acute progressive renal failure requires an appropriate antifungal drug considering the possibility of disseminated Trichosporon.

Topics: Acute Disease; Aged; Amphotericin B; Echinocandins; Humans; Kidney Tubules; Lipopeptides; Male; Micafungin; Neutropenia; Primary Myelofibrosis; Trichosporon; Trichosporonosis

The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug-drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting.. This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2-3 times weekly) in patients with acute leukemia and allogeneic SCT recipients.. A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection.. In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings.

Topics: Acute Disease; Administration, Intravenous; Adult; Aged; Antifungal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Echinocandins; Female; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Kidney; Leukemia; Lipopeptides; Liver Function Tests; Male; Micafungin; Middle Aged; Mycoses; Retrospective Studies; Young Adult

A 73-year-old man (height, 158.2 cm; weight, 49.8 kg) presented with upper abdominal tenderness after 3 weeks of treatment with 150 mg/d of micafungin (3 mg/kg . d) (Mycamine, Astellas Pharma US Inc., Deerfield, Illinois) intravenously for pulmonary aspergillosis accompanied by [DOSAGE ERROR CORRECTED] pulmonary Mycobacterium avium complex (MAC) infection. Pulmonary aspergillosis was noninvasively diagnosed by a fungus lump in a cavity in the right upper lung field with a high value of 1,3-beta-D-glucan and a positive result for aspergillosis antigen. The patient had a medical history of gastrectomy due to gastric cancer and idiopathic thrombocytopenic purpura (ITP). He had been prescribed 800 mg/d of clarithromycin, 400 mg/dL of rifampicin, and 750 mg/d of ethambutol hydrochloride for pulmonary MAC infection for 2 years and 5 mg/d of prednisolone for ITP for 7 years. No traditional or homeopathic medicine had been received/administered. Laboratory tests at the onset of abdominal pain revealed a white blood cell count of 4300/microL with 51% neutrophils. There was no eosinophilia. Platelet count was 15,100/muL, with normal coagulation. Immunoglobulin G and immunoglobulin M were 1720 and 154 mg/dL, respectively. The patient had no history of allergy, biliary tract disease, hyperlipidemia, or hypercalcemia. He did not report alcohol use. The laboratory findings, magnetic resonance imaging, and upper abdominal tenderness were consistent with acute pancreatitis. After cessation of all drugs, his symptoms improved with bowel rest and parenteral nutrition. His laboratory measurements normalized thereafter. All drugs, except micafungin, were readministered for pulmonary MAC infection and ITP, and itraconazole was administered for pulmonary aspergillosis after the recovery from pancreatitis. During 16 months of follow-up, the pancreatitis did not recur.. We performed a literature search of all available English-language articles published on MEDLINE between January 1966 and January 2007 using the key terms micafungin (text and indexed terms) and pancreatitis (text and indexed terms). Based on the search of MEDLINE, there have been no reports of acute pancreatitis associated with micafungin. The Naranjo adverse drug reaction (ADR) probability scale was used to assess the probability of micafungin-associated acute pancreatitis. A score of 6 was obtained, indicating a probable ADR from micafungin treatment.. We report a case of acute pancreatitis probably associated with micafungin use in an elderly patient.

Topics: Acute Disease; Aged; Antifungal Agents; Aspergillosis; Echinocandins; Humans; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Mycobacterium avium-intracellulare Infection; Pancreatitis; Peptides, Cyclic

We describe a 55-year-old man with acute myelogenous leukemia who developed breakthrough Trichosporon asahii fungemia during 5 days of micafungin treatment. Although the patient's clinical condition improved considerably after the start of voriconazole treatment, blood culture results remained positive for T. asahii for 3 days, and fever persisted for 7 days thereafter. The patient achieved complete hematological remission, and he received successful consolidation chemotherapy without developing Trichosporon infection with the prophylactic use of voriconazole therapy. This case report illustrates that voriconazole may be useful in the treatment of disseminated T. asahii infection in neutropenic patients.

Topics: Acute Disease; Antifungal Agents; Aspergillosis; Echinocandins; Fungemia; Humans; Leukemia, Myeloid; Lipopeptides; Lipoproteins; Male; Micafungin; Middle Aged; Mycoses; Peptides, Cyclic; Pyrimidines; Triazoles; Trichosporon; Voriconazole

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.. Haematology department and bone marrow transplantation unit.. 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.. 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.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Drug Evaluation; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Itraconazole; Leukemia, Myeloid; Lipopeptides; Lipoproteins; Male; Micafungin; Mucormycosis; Multiple Organ Failure; Peptides, Cyclic; Periodontal Abscess; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sinusitis; Splenectomy; Systemic Inflammatory Response Syndrome; Transplantation, Homologous