Morita Atsuho, Namkoong Ho, Yagi Kazuma, Asakura Takanori, Hosoya Makoto, Tanaka Hiromu, Lee Ho, Ogawa Takunori, Kusumoto Tatsuya, Azekawa Shuhei, Nakagawara Kensuke, Kamata Hirofumi, Ishii Makoto, Fukunaga Koichi, Ozawa Hiroyuki, Hasegawa Naoki
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
Infect Drug Resist. 2022 Jul 26;15:4001-4011. doi: 10.2147/IDR.S373783. eCollection 2022.
Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for effect while minimising systemic adverse effects, was recently approved for treating complex (MAC) infections. The international Phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few studies have examined the efficacy and adverse effects of ALIS using real-world data. We identified the clinical outcome and adverse effects of ALIS in the early phase of treatment, for more effective and safe use in clinical practice.
The study population consisted of patients with MAC lung disease (MAC-LD), introduced to ALIS therapy after July 2021 at Keio University Hospital due to poor response to multidrug therapy. The sputum smear/culture results, symptoms, adverse effects, and the serum amikacin concentrations of the early phase of ALIS inhalation therapy were examined.
A total of 11 patients (9 women; median age 64.6 years) were included in this study. The median disease duration of MAC-LD was 13.7 years, and all patients exhibited a positive culture at the beginning of ALIS inhalation. Three of the six patients (50.0%) who were initially sputum-smear-positive were confirmed to have become sputum-smear-negative within one month, including one culture conversion. ALIS inhalation therapy caused some adverse effects in nine patients (81.8%); however, no serious systemic adverse effects were observed. The most common adverse effect was hoarseness (72.7%), which mostly occurred around 1 week after initiation. The medians of peak serum amikacin concentrations were 1.4 and 2.3 μg/mL for the first and third inhalations, respectively. Trough serum concentrations just before the third inhalation were <1.2 μg/mL in all patients.
ALIS therapy might be a treatment option for patients with refractory MAC infection with long disease duration and a poor response to guideline-based therapy.
阿米卡星脂质体吸入混悬液（ALIS）能有效使阿米卡星到达肺周边发挥作用，同时将全身不良反应降至最低，最近被批准用于治疗复杂性（MAC）感染。国际3期开放标签临床试验显示了有前景的结果，有助于痰培养转阴，但很少有研究使用真实世界数据来检验ALIS的疗效和不良反应。我们确定了ALIS在治疗早期的临床结局和不良反应，以便在临床实践中更有效、安全地使用。
研究人群包括MAC肺病（MAC-LD）患者，这些患者因对多药治疗反应不佳于2021年7月后在庆应义塾大学医院开始接受ALIS治疗。对ALIS吸入治疗早期的痰涂片/培养结果、症状、不良反应及血清阿米卡星浓度进行了检查。
本研究共纳入11例患者（9例女性；中位年龄64.6岁）。MAC-LD的中位病程为13.7年，所有患者在开始ALIS吸入时痰培养均为阳性。最初痰涂片阳性的6例患者中有3例（50.0%）在1个月内被确认为痰涂片转阴，其中1例实现了培养转阴。9例患者（81.8%）在ALIS吸入治疗中出现了一些不良反应；然而，未观察到严重的全身不良反应。最常见的不良反应是声音嘶哑（72.7%），大多在开始治疗后1周左右出现。首次和第三次吸入时血清阿米卡星峰值浓度的中位数分别为1.4 μg/mL和2.3 μg/mL。所有患者在第三次吸入前的谷浓度均<1.2 μg/mL。
对于病程长且对基于指南的治疗反应不佳的难治性MAC感染患者，ALIS治疗可能是一种治疗选择。
