Moore J E, Mastoridis P
Northern Ireland Public Health Laboratory, Department of Bacteriology, Belfast City Hospital, Belfast, UK.
Respiratory Department, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
J Clin Pharm Ther. 2017 Jun;42(3):259-267. doi: 10.1111/jcpt.12521. Epub 2017 Apr 4.
Pseudomonas aeruginosa is the leading cause of lung infection in patients with cystic fibrosis (CF) and is associated with significant morbidity and mortality. Antibiotics are regarded as the foundational pharmacological treatment for the suppressive management of chronic P. aeruginosa infections and to eradicate the first infection by P. aeruginosa. Inhalation remains a preferred route for drug administration, providing direct access to the site of infection while minimizing systemic side effects. Effective suppressive management of P. aeruginosa infections, however, requires an understanding of the location of the bacteria in the lungs and consideration of the factors that could limit access of the inhaled antibiotic to the infected area. This review provides a systematic assessment of the scientific literature to gain insight into the location of P. aeruginosa in the lungs of patients with CF and its clinical implications. The characteristics of antibiotic inhalation systems are also discussed in this context.
We reviewed evidence-based literature from both human and animal studies in which P. aeruginosa lung location was reported. Relevant publications were identified through a screening strategy and summarized by reported P. aeruginosa location.
Most areas of the conductive and respiratory zones of the lungs are susceptible to P. aeruginosa colonization. Deposition of an inhaled antibiotic is dependent on the device and formulation characteristics, as well as the ability of the patient to generate sufficient inhaled volume. As patients with CF often experience a decline in lung function, the challenge is to ensure that the inhaled antibiotic can be delivered throughout the bronchial tree.
An effective drug delivery system that can target P. aeruginosa in both the respiratory and conductive zones is required. The chosen inhalation device should also offer a drug formulation that can be quickly and effectively delivered to specific lung locations, with minimal inspiratory effort from the patient.
铜绿假单胞菌是囊性纤维化(CF)患者肺部感染的主要病因,与显著的发病率和死亡率相关。抗生素被视为慢性铜绿假单胞菌感染抑制性治疗以及根除首次铜绿假单胞菌感染的基础药物治疗方法。吸入仍然是首选的给药途径,可直接到达感染部位,同时将全身副作用降至最低。然而,要有效抑制铜绿假单胞菌感染,需要了解肺部细菌的位置,并考虑可能限制吸入抗生素进入感染区域的因素。本综述对科学文献进行了系统评估,以深入了解CF患者肺部铜绿假单胞菌的位置及其临床意义。在此背景下,还讨论了抗生素吸入系统的特点。
我们回顾了来自人类和动物研究的循证文献,这些文献报告了铜绿假单胞菌在肺部的位置。通过筛选策略确定相关出版物,并按报告的铜绿假单胞菌位置进行总结。
肺部传导区和呼吸区的大多数区域都易受铜绿假单胞菌定植。吸入抗生素的沉积取决于装置和制剂特性,以及患者产生足够吸入量的能力。由于CF患者的肺功能通常会下降,挑战在于确保吸入抗生素能够送达整个支气管树。
需要一种能够靶向呼吸区和传导区铜绿假单胞菌的有效给药系统。所选的吸入装置还应提供一种药物制剂,能够快速有效地送达特定肺部位置,且患者吸气努力最小。