Davis Kala K, Kao Peter N, Jacobs Susan S, Ruoss Stephen J
Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA, USA.
BMC Pulm Med. 2007 Feb 23;7:2. doi: 10.1186/1471-2466-7-2.
Current systemic therapy for nontuberculous mycobacterial pulmonary infection is limited by poor clinical response rates, drug toxicities and side effects. The addition of aerosolized amikacin to standard oral therapy for nontuberculous mycobacterial pulmonary infection may improve treatment efficacy without producing systemic toxicity. This study was undertaken to assess the safety, tolerability and preliminary clinical benefits of the addition of aerosolized amikacin to a standard macrolide-based oral treatment regimen.
Six HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Patients were monitored clinically and serial sputum cultures were obtained to assess response to therapy. Symptomatic improvement with radiographic stabilization and eradication of mycobacterium from sputum were considered markers of success. Of the six patients treated with daily aerosolized amikacin, five responded to therapy. All of the responders achieved symptomatic improvement and four were sputum culture negative after 6 months of therapy. Two patients became re-infected with Mycobacterium avium intracellulare after 7 and 21 months of treatment. One of the responders who was initially diagnosed with Mycobacterium avium intracellulare became sputum culture positive for Mycobacterium chelonae resistant to amikacin after being on intermittent therapy for 4 years. One patient had progressive respiratory failure and died despite additional therapy. There was no evidence of nephrotoxicity or ototoxicity associated with therapy.
Aerosolized delivery of amikacin is a promising adjunct to standard therapy for pulmonary nontuberculous mycobacterial infections. Larger prospective trials are needed to define its optimal role in therapy of this disease.
目前非结核分枝杆菌肺部感染的全身治疗受到临床反应率低、药物毒性和副作用的限制。在非结核分枝杆菌肺部感染的标准口服治疗中添加雾化阿米卡星可能会提高治疗效果而不产生全身毒性。本研究旨在评估在基于大环内酯类的标准口服治疗方案中添加雾化阿米卡星的安全性、耐受性和初步临床益处。
6例鸟分枝杆菌胞内复合群肺部感染且标准治疗失败的HIV阴性患者,除接受基于大环内酯类的标准多药口服治疗外,每天给予15mg/kg的雾化阿米卡星。对患者进行临床监测并获取系列痰培养以评估治疗反应。症状改善、影像学稳定以及痰中分枝杆菌清除被视为治疗成功的标志。在接受每日雾化阿米卡星治疗的6例患者中,5例对治疗有反应。所有有反应的患者症状均有改善,4例在治疗6个月后痰培养转阴。2例患者在治疗7个月和21个月后再次感染鸟分枝杆菌胞内复合群。1例最初诊断为鸟分枝杆菌胞内复合群感染的有反应患者在接受间歇治疗4年后,痰培养对阿米卡星耐药的龟分枝杆菌呈阳性。1例患者尽管接受了额外治疗仍出现进行性呼吸衰竭并死亡。没有证据表明治疗与肾毒性或耳毒性有关。
雾化吸入阿米卡星是肺部非结核分枝杆菌感染标准治疗的一种有前景的辅助治疗方法。需要更大规模的前瞻性试验来确定其在该疾病治疗中的最佳作用。