Kurahara Yu, Yoshida Shiomi, Osugi Asami, Tanaka Yuya, Kobayashi Takehiko, Mitsuhashi Toshiharu, Kawasaki Yohei, Mitarai Satoshi, Tsuyuguchi Kazunari
Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
Department of Infectious Diseases, NHO Kinki Chuo Chest Medical Center, Osaka, Japan.
Open Forum Infect Dis. 2025 Mar 1;12(3):ofaf118. doi: 10.1093/ofid/ofaf118. eCollection 2025 Mar.
Amikacin liposome inhalation suspension (ALIS) is key for treating refractory complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.
We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.
We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype ( = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66-70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had mutations.
Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD.
阿米卡星脂质体吸入混悬液（ALIS）是治疗难治性复杂性肺部疾病（MAC-PD）的关键药物。然而，按亚型划分的微生物学疗效尚不清楚。ALIS给药期间阿米卡星（AMK）耐药的频率和机制也不明确。
我们回顾性分析了在日本国立医院九州中央胸部医疗中心接受ALIS治疗至少6个月作为基于指南治疗辅助手段的难治性MAC-PD患者的数据。我们研究了ALIS的疗效，并分析了基因表达和AMK耐药的频率。
我们纳入了44例患者（中位年龄72.0岁）：19例（43.2%）为非空洞结节性支气管扩张（NC-NB）亚型，25例（56.8%）为空洞亚型。总体而言，痰培养转阴率为56.8%（25/44）：NC-NB亚型为84.2%（16/19），空洞亚型为36.0%（9/25）（P = 0.001）。在间歇给药期间，转阴率为50.0%（9/18）。在C反应蛋白（CRP）≥1 mg/dL、空洞亚型且对克拉霉素（CLM）耐药的患者中，与CRP<1 mg/dL、NC-NB亚型且对CLM敏感的患者相比，持续培养阳性的风险比为10.81（95%CI，1.66 - 70.40）。在所有参与者中，15.9%（7/44）的分离株对AMK耐药（最低抑菌浓度≥128 µg/mL），其中71.4%（5/7）有基因突变。
与空洞型MAC-PD病例相比，包含ALIS的治疗方案在NC-NB型中实现了更高的培养转阴率。高CRP水平、空洞性疾病和CLM耐药预示着培养持续阳性。ALIS给药期间获得的AMK耐药可能会限制难治性MAC-PD的治疗选择。
