micafungin and Chronic-Disease

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

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

Chronic invasive aspergillosis of the sinus is frequently fatal in the absence of early surgical and chemotherapeutic intervention because of its invasion of vascular tissue. We attempted to control a case of inoperable invasive aspergillosis of the sinus with micafungin and itraconazole oral solution. We prescribed a daily oral dose of 400 mg of itraconazole, which is twice the usual dose, and monitored the serum concentration of the drug. Finally, we were able to control the spread of the lesion. This case indicates that combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution is an alternative treatment strategy for inoperable invasive aspergillosis of the sinus.

Topics: Aged; Antifungal Agents; Aspergillosis; Central Nervous System Fungal Infections; Chronic Disease; Echinocandins; Female; Humans; Itraconazole; Lipopeptides; Micafungin; Paranasal Sinus Diseases; Radiography

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

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

The rising incidence of pulmonary aspergillosis is a major clinical concern. However, only a limited number of antifungal drugs are available in Japan that are effective for pulmonary Aspergillus infections. Micafungin (MCFG), a newly developed echinocandin family antifungal drug, has potent antifungal activity in vitro, but few reports detailing its clinical effectiveness have been published to date. A retrospective study was performed using data from nine patients (seven males and two females) with chronic invasive forms of pulmonary aspergillosis, who were treated with either MCFG alone or together with other antifungal drugs between April 2003 and March 2004. The overall efficacy of the treatments was evaluated in the terms of clinical, mycological, serological and radiological responses. The average age of the patients was 61.9 (20-83) years old. Four patients received only MCFG and the remaining five patients were treated with MCFG in combination with amphotericin B (AMB) only (1 patient), itraconazole (ITC) only (2 patients) or AMB backed up by ITC during AMB discontinuation periods (2 patients). The mean duration of MCFG administration was 59.2 (28-96) days. Overall, the treatment was judged to have been effective for seven of nine patients. No patient's condition deteriorated in response to treatment. Administration of MCFG alone was judged to have been effective in three of four patients. No notable adverse effects were documented during MCFG administration. These data suggest that MCFG may be an effective and safe antifungal drug for the treatment of chronic invasive forms of pulmonary aspergillosis.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Chronic Disease; Drug Therapy, Combination; Echinocandins; Female; Humans; Itraconazole; Japan; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Middle Aged; Peptides, Cyclic; Radiography; Retrospective Studies; Treatment Outcome

A 63-year-old man was admitted to our hospital because he complained of fever and productive cough; this was associated with cavitary infiltrates on his chest X-ray. Although several antibiotics were given, his symptoms did not improve. Bronchofiberscope investigation yielded Aspergillus fumigatus; thus, he was diagnosed with chronic necrotizing pulmonary aspergillosis. Itraconazole, 200 mg/day, was given, and his symptoms and infiltrates on chest X-ray gradually improved. After 2 months of treatment, new infiltrates appeared on a chest X-ray. Antibacterial agents had also shown no effect, and voriconazole was substituted for itraconazole. However, the infiltrates progressed in spite of the voriconazole administration. We added micafungin to the voriconazole treatment. Both his symptoms and the infiltrates on chest X-rays improved. Because voriconazole is thought to be the most effective agent against Aspergillus spp., it is difficult to treat cases that are refractory to voriconazole. The treatment of this case provides invaluable information on how to treat pulmonary aspergillosis related to diseases other than hematologic malignancies.

Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Chronic Disease; Drug Resistance, Multiple, Fungal; Echinocandins; Humans; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Middle Aged; Necrosis; Pyrimidines; Radiography; Triazoles; Voriconazole

The patient was a 42-year-old man who visited a physician with fever, and was diagnosed with pulmonary abscess. Antibiotic therapy was ineffective, and he was referred to our hospital. Chest CT scanning revealed a lesion with cavity formation with an infiltrative shadow in the right upper lobe, and another infiltrative shadow in the left upper lobe. Chronic necrotizing pulmonary aspergillosis (CNPA) was diagnosed on the basis of positive culture of bronchial lavage specimens and positive serological test results for Aspergillus, in addition to the clinical and radiographic features. Intravenous administration of micafungin (MCFG) was initiated with combination therapy of percutaneous cavity drainage, inhaled amphotericin B and oral itraconazole. Clinical symptoms and findings gradually improved, and he was discharged after 40 days of MCFG therapy. MCFG was safe and effective therapy in this case, and may be considered a new therapeutic option for CNPA.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Chronic Disease; Drug Therapy, Combination; Echinocandins; Humans; Itraconazole; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Necrosis; Peptides, Cyclic