University of Medicine and Pharmacy Grigore T Popa Iasi, Interdisciplinarity, Str. Universităţii nr 16, Iasi, 700115, Romania.
Expert Opin Investig Drugs. 2013 Feb;22(2):267-76. doi: 10.1517/13543784.2013.748034. Epub 2012 Nov 24.
The chronic airway infection with Pseudomonas aeruginosa (PA) is a risk factor for rapid disease progression in various chronic pulmonary diseases including cystic fibrosis or chronic obstructive pulmonary disease. Inhaled antibiotics are able to treat effectively such chronic airway infections, and MP-376 is currently in late-stage clinical development for such an indication.
Review of the existing preclinical and clinical data on MP-376, with a focus on the efficacy and safety of the compound on chronic airways infections due to PA.
Chronic airways infection with PA represents a therapeutic challenge because of its own complex mechanisms of defense, because of the rapid development of antibiotic resistance and by the fact that systemic antibiotics are not always able to achieve appropriate concentrations at lung level. Inhaled antibiotics (tobramycin, aztreonam, etc.) represent optimal alternatives to their systemic homologs due to their better penetrability in the lungs and due to the lower systemic exposure. Inhaled levofloxacin which is currently investigated for chronic airways infection might be another possible antipseudomonal inhaled therapy.
铜绿假单胞菌（PA）的慢性气道感染是包括囊性纤维化或慢性阻塞性肺疾病在内的各种慢性肺部疾病快速疾病进展的危险因素。吸入抗生素能够有效治疗这种慢性气道感染，目前 MP-376 正在进行针对这种适应症的后期临床开发。
对 MP-376 的现有临床前和临床数据进行综述，重点介绍该化合物在 PA 引起的慢性气道感染方面的疗效和安全性。
PA 的慢性气道感染是一个治疗挑战，因为其自身的防御机制复杂，抗生素耐药性迅速发展，并且全身抗生素并不总是能够在肺部达到适当的浓度。由于其在肺部的渗透性更好，并且全身暴露量更低，吸入抗生素（妥布霉素、氨曲南等）是全身类似物的最佳替代品。目前正在研究用于慢性气道感染的左氧氟沙星可能是另一种潜在的抗假单胞菌吸入治疗方法。
