micafungin and Pulmonary-Aspergillosis

In spite of recent advances in chemotherapy, the treatment of pulmonary aspergilloma remains unsatisfactory. To evaluate the clinical efficacy and safety of combination therapy for pulmonary aspergilloma, we conducted a multi-institutional prospective study using micafungin (MCFG) and itraconazole (ITCZ). Adult patients who fulfilled the criteria for pulmonary aspergilloma were enrolled in this study. After patient consent had been obtained, intravenous MCFG 150 mg/day and an oral capsule of ITCZ 200 mg/day were administered for at least 1 month. The primary endpoint was the response assessed using an algorithm that incorporated the levels of improvement by evaluating clinical symptoms and signs, mycological and serological tests, and diagnostic imaging. A total of 17 patients were enrolled from three facilities. The response rate to the combination therapy was 58.8% (10/17). The long-term control in the group of patients who responded to treatment was better than that in the group of patients who did not respond. Adverse events occurred in 6 of the 17 patients (35.3%), but there were no severe adverse events. MCFG-ITCZ combination therapy appeared to be relatively safe and effective in patients with pulmonary aspergilloma.

Topics: Aged; Aged, 80 and over; Antifungal Agents; Aspergillus fumigatus; Drug Therapy, Combination; Echinocandins; Female; Humans; Itraconazole; Lipopeptides; Male; Micafungin; Middle Aged; Prospective Studies; Pulmonary Aspergillosis; Radiography, Thoracic; Treatment Outcome

Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to Aspergillus spp. The evidence regarding CPA treatment is limited. We conducted a randomized, multicenter, open-label trial comparing intravenous micafungin (MCFG) of 150-300 mg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily for the treatment of 107 in patients with CPA to compare the efficacy and safety of both drugs as initial treatment in Japan. Treatment effectiveness was defined by clinical, mycological, radiological and serological responses 2 weeks after the initial administration and at the end of therapy. The total of 50 and 47 patients were assigned to the MCFG and VRCZ groups, respectively. The difference in efficacy rates between MCFG and VRCZ was not significant, either after 2 weeks [68.0% vs. 58.7%; the absolute difference, 9.3% with a 95% confidence interval (CI), -9.97 to 28.58, P = 0.344] or at the end of therapy (60.0% vs. 53.2%; the absolute difference, 6.8% with a 95% CI, -12.92 to 26.54, P = 0.499). In the safety evaluation, fewer adverse events occurred in the MCFG than VRCZ group (26.4% vs. 61.1%, P = 0.0004). MCFG was as effective as VRCZ and significantly safer than as an initial treatment of CPA. (UMIN Clinical Trials Registry number, UMIN000001786.).

Topics: Aged; Aged, 80 and over; Antifungal Agents; Aspergillus; Chronic Disease; Echinocandins; Female; Humans; Infusions, Intravenous; Japan; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Pulmonary Aspergillosis; Pyrimidines; Radiography; Treatment Outcome; Triazoles; Voriconazole

A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load. The grafts were implanted successfully, but the patient developed an invasive fungal infection. A lung biopsy was performed, and the pathogen was confirmed to be Aspergillus terreus via gene sequencing and analysis. The combined treatment of micafungin and posaconazole had good efficacy in this case, and this patient now receives close follow-up and receives oral posaconazole for antifungal maintenance treatment.

Topics: Antifungal Agents; Hematopoietic Stem Cell Transplantation; Humans; Male; Micafungin; Myelodysplastic Syndromes; Postoperative Complications; Pulmonary Aspergillosis; Remission Induction; Triazoles; Young Adult

Intravenous micafungin has been reported as a treatment alternative in patients with chronic pulmonary aspergillosis (CPA) where long-term oral triazole therapy is unfeasible.. We evaluated the safety and efficacy of micafungin administered via the outpatient parenteral antimicrobial therapy (OPAT) service for the treatment of CPA.. We included all CPA patients who received micafungin via OPAT between April 2016 and March 2018. Data on adverse events and line-related complications, and Quality of Life (QoL) scores at the start of micafungin course and 3 months later were extracted. Improvements in QoL were defined as an improvement of ≥4 points in at least one modality (symptom, impact, activity, total) in the St George's QoL score. A stable QoL score was defined as a change in score of <4 points in either direction whilst deterioration was defined as an increase of ≥4 points.. There were 20 OPAT episodes involving 18 patients with a median duration of micafungin therapy of 21 (range: 4-248) days. Improvement or stability in the symptoms, activity, impact and total score was seen in 14 (78%), 12 (67%), 9 (50%) and 9 (50%) of the patients, respectively. However, half of the patients reported deterioration in the impact domain and total scores. By self-assessment, patients who categorised themselves as "poor" were comparable at the start of OPAT and at 3 months (43% vs 50%, McNemar's P = 0.7). Adverse events attributable to micafungin were recorded in 3 (14.3%) episodes.. Micafungin may be safely administered via an OPAT service. Micafungin therapy was associated with an improvement or stability in QoL scores in at least 50% of the patients across the four domains.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Ambulatory Care; Antifungal Agents; Chronic Disease; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Micafungin; Middle Aged; Outpatients; Pulmonary Aspergillosis; Quality of Life; Retrospective Studies; Treatment Outcome

A bottlenose dolphin (Tursiops truncatus) housed in the Port of Nagoya Public Aquarium (PNPA) presented with symptomatic pneumonia caused by Aspergillus fumigatus. The dolphin was treated with micafungin. On days 2 and 11 after the first administration of micafungin, results from a physical examination and laboratory test indicated a decline of body temperature (BT) and leukopenia, with lowest BT, white blood cells (WBCs), and segmented neutrophils (SEGs) of 34.2°C, 600 cells/µl, and 67 cells/µl, respectively. BT, WBCs, and SEGs returned to normal range after administration of granulocyte colony stimulating factor (G-CSF). To the best of our knowledge, this is the first report of micafungin-induced decline of BT and leukopenia that was successfully treated with G-CSF in a bottlenose dolphin.

Topics: Animals; Bottle-Nosed Dolphin; Female; Leukopenia; Micafungin; Pneumonia; Pulmonary Aspergillosis

Aspergillosis has been the prevailing deep-seated mycosis in Japan since the 1990s. Although micafungin (MCFG) has been approved in Japan for the management of patients with such infections caused by Candida and Aspergillus species, there are relatively few reports on its use in patients with chronic pulmonary aspergillosis (CPA). Therefore, we conducted a prospective observational study to evaluate the efficacy and safety of the use of MCFG in Japanese patients with CPA. The efficacy of the antifungal was assessed on the basis of improvements in clinical symptoms and radiological findings. In addition, adverse events, including abnormal laboratory findings were determined. The overall clinical efficacy rate was 68.4% (26/38 patients), which is comparable to the results obtained in clinical trials for marketing approval conducted in Japan. Although adverse drug reactions were observed in six patients (15.8%), they were not serious. The most common of these reactions was abnormal liver functions. No relationship between the incidence of adverse drug reactions and age of the patients, MCFG dose, or duration of treatment was observed. Consequently, MCFG has favorable efficacy and safety profiles in Japanese CPA patients with various backgrounds.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Chemical and Drug Induced Liver Injury; Chronic Disease; Echinocandins; Female; Humans; Japan; Lipopeptides; Male; Micafungin; Middle Aged; Prospective Studies; Pulmonary Aspergillosis; Treatment Outcome

A 70-year-old Japanese man with chronic kidney disease under treatment with oral prednisolone for organizing pneumonia developed pulmonary aspergilloma. The patient was started on micafungin (MCFG), with no addition of any other new drug. About 5 weeks later, aggravation of his normocytic anemia associated with a low reticulocyte count was observed. Bone marrow puncture and biopsy revealed intense hypoplasia of the erythroblasts. As there was no evidence of malignancy, human parvovirus B19 infection, autoimmune diseases or hemorrhage, the patient was diagnosed as having acquired pure red cell aplasia (PRCA). The anemia improved along with an increase of the reticulocyte count to the normal level within 12 weeks of discontinuation of the MCFG therapy. The patient showed no evidence subsequently of any recurrence of the normocytic normochromic anemia or relapse of the PRCA. This is the first reported case of PRCA associated with MCFG.

Topics: Aged; Antifungal Agents; Bone Marrow; Cryptogenic Organizing Pneumonia; Echinocandins; Humans; Immunosuppressive Agents; Lipopeptides; Male; Micafungin; Prednisolone; Pulmonary Aspergillosis; Red-Cell Aplasia, Pure

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Administration Schedule; Echinocandins; Fatal Outcome; Female; Humans; Lipopeptides; Liposomes; Lymphoma, T-Cell; Maxillary Sinus Neoplasms; Micafungin; Middle Aged; Nasal Cavity; Nose Neoplasms; Pulmonary Aspergillosis

Monotherapy and combination therapy were compared using optimal doses of liposomal amphotericin B, micafungin, or caspofungin in Aspergillus fumigatus pulmonary and disseminated infections. Mice were challenged intravenously (2.8 x 10(4) to 5.7 x 10(4) conidia) or intranasally (5.8 x 10(7) conidia) with A. fumigatus. Drugs (5, 10, or 15 mg/kg of body weight) were given for 3 or 6 days as single, concomitant, or sequential therapy (i.e., days 1 to 3 and then days 4 to 6). Mice were monitored for survival, and tissues were assayed for fungal burden and drug concentrations. Treatments starting 24 h postchallenge significantly prolonged survival in disseminated aspergillosis (P < 0.002), but only liposomal amphotericin B treatments or treatments beginning with liposomal amphotericin B increased survival to 100% in the pulmonary aspergillosis model. Fungi in kidneys and spleens (disseminated) and lungs (pulmonary) were significantly decreased (P < or = 0.04) by liposomal amphotericin B, liposomal amphotericin B plus echinocandin, or liposomal amphotericin B prior to echinocandin. In the disseminated infection, liposomal amphotericin B and micafungin (10 or 15 mg/kg) had similar kidney drug levels, while in the spleen, 5 and 15 mg/kg liposomal amphotericin B gave higher drug levels than micafungin (P < 0.02). In the pulmonary infection, drug levels in lungs and spleen with 5-mg/kg dosing were significantly higher with liposomal amphotericin B than with caspofungin (P < or = 0.002). In summary, treatment of A. fumigatus infections with liposomal amphotericin B plus echinocandin or liposomal amphotericin B prior to echinocandin was as effective as liposomal amphotericin B alone, and a greater decrease in the fungal burden with liposomal amphotericin B supports using liposomal amphotericin B prior to echinocandin.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillus fumigatus; Echinocandins; Female; Mice; Microbial Sensitivity Tests; Pulmonary Aspergillosis

Topics: Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candida tropicalis; Candidiasis; Drug Therapy, Combination; Echinocandins; Follow-Up Studies; Fungemia; Humans; Infant; Lipopeptides; Male; Micafungin; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pulmonary Aspergillosis; Pyrimidines; Tomography, X-Ray Computed; Triazoles; Voriconazole

A 62-year-old man with empyema caused by Aspergillus fumigatus was successfully treated with a combination of voriconazole (VRCZ) and micafungin (MCFG). Data regarding the penetration of antifungal agents into pleural fluid are limited. Thus, we measured the concentration of VRCZ and MCFG in his plasma and pleural fluid. Penetration of VRCZ and MCFG into the pleural fluid was excellent. Therefore, the combination therapy using VRCZ and MCFG may contribute to successful management of Aspergillus empyema.

Topics: Aspergillus fumigatus; Drug Therapy, Combination; Echinocandins; Empyema, Pleural; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Pleural Effusion; Pulmonary Aspergillosis; Pyrimidines; Triazoles; Voriconazole

We evaluated both the short-and long-term efficacy of micafungin in patients with chronic pulmonary aspergillosis (CPA). We treated 26 patients with CPA, 19 with chronic necrotizing pulmonary aspergillosis (CNPA) and 7 with aspergilloma, with micafungin between February 2003 and September 2005. On completion of treatment (short-term efficacy evaluation), the efficacy rates of micafungin for CNPA and aspergilloma were 52.6% (10/19) and 71.4% (5/7), respectively, and the overall efficacy rate was 57.7% (15/26). Long-term efficacy was evaluable in 25 of 26 patients, and 15 patients, who responded favorably to micafungin, received maintenance therapy with itraconazole (200mg). In long-term efficacy evaluation, 10 patients were unchanged, but in 5 patients symptoms were exacerbated after 1.8 months (median time). This result suggests that establishing effective maintenance therapy, as well as acute-phase therapy, is important in the treatment of patients with CPA.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Chronic Disease; Echinocandins; Female; Humans; Itraconazole; Lipopeptides; Male; Micafungin; Middle Aged; Pulmonary Aspergillosis