分枝杆菌脓肿的治疗结果(Mab,也称为脓肿分枝杆菌)疾病仍然不能令人满意,主要是由于药物毒性问题,耐受性,和功效。由于其高基线抗生素耐药性,治疗单克隆抗体疾病具有挑战性。静脉治疗的初始需求,药物耐受性差。Omadacycline,一种新的四环素,积极对抗Mab。由于任何对单克隆抗体有效的新抗生素预计将与其他抗生素联合使用,我们评估了包含omadacycline的两种三联药物组合的疗效,奥马环素+阿米卡星+亚胺培南,在单克隆抗体肺病小鼠模型中,奥马环素+氯法齐明+利奈唑胺对抗两种当代单克隆抗体临床分离株。感染后1周开始服用抗生素,每天服用,治疗完成时肺部的Mab负担作为终点。与未经治疗的小鼠相比,单独使用Omadacycline适度降低了Mab水平,并保持了更好的健康。通常患有感染。奥马环素+氯法齐明+利奈唑胺组合在6周内显示出立即的杀菌活性和增强的功效,特别是针对更具抗性的菌株(M9507)。然而,氯法齐明+利奈唑胺组合缺乏早期杀菌活性。当与阿米卡星和亚胺培南联合使用时,奥马环素治疗4周后未改善该方案的有效性。我们的研究表明,在延长的治疗时间内,奥马环素氯法齐明利奈唑胺表现出明显的杀菌活性。然而,在阿米卡星和亚胺培南中加入omadacycline并不能提高治疗方案在4周内对评估的临床分离株的有效性.需要对Mab病患者进行进一步研究,以确定最有效的含omadacycline的方案。IMPORTANCEMycobacterioides脓肿是一种常见的环境细菌,会导致肺功能受损的人感染,包括支气管扩张症患者,囊性纤维化,慢性阻塞性肺疾病,削弱了免疫系统,尤其是老年人。由于目前抗生素的疗效和毒性有限,治疗脓肿分枝杆菌具有挑战性。这往往需要长期使用。Omadacycline,一种新的抗生素,显示出对脓肿M.的承诺。使用模拟人类脓肿分枝杆菌病的小鼠模型,我们研究了包括奥马环素和推荐的抗生素的有效性.在氯法齐明和利奈唑胺中加入奥马环素可显著改善治疗结果,迅速清除肺部的细菌,并保持有效性。这种口服组合对患者是方便的。然而,在阿米卡星和亚胺培南中加入omadacycline并没有改善4周内的治疗效果。有必要对脓肿分枝杆菌患者进行进一步研究,以优化基于omadacycline的该疾病的治疗策略。
Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline +
clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline +
clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the
clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen\'s effectiveness over 4 weeks of treatment. Our study showed that omadacycline +
clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to
clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.