Westerman E M, Le Brun P P H, Touw D J, Frijlink H W, Heijerman H G M
Central Hospital Pharmacy The Hague, The Hague, The Netherlands.
J Cyst Fibros. 2004 Mar;3(1):23-8. doi: 10.1016/j.jcf.2003.12.005.
Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin. However, nebulized colistin can cause bronchoconstriction in CF patients. Therefore, in the progress of developing a dry powder formula, the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects. To investigate the side effects, a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF-patients.
Nine CF-patients chronically infected with P. aeruginosa participated in a double blind, randomized cross over study. On two visits to the outpatient clinic, patients were submitted to either nebulized colistin sulphate or colistin sulphomethate solution. Lung function tests were performed immediately before and 15 and 30 min after nebulization.
Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), -5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate (P < 0.05). Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough.
Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa. Colistin sulphomethate is the drug of choice for pulmonary administration of colistin.
对于长期感染铜绿假单胞菌的囊性纤维化(CF)患者,雾化吸入多黏菌素是抗菌治疗方法之一。多黏菌素干粉吸入可能是雾化吸入多黏菌素的一个有吸引力的替代方法。然而,雾化吸入多黏菌素可导致CF患者支气管收缩。因此,在开发干粉配方的过程中,吸入器及其内容物的选择应以最佳疗效和尽可能少的副作用为指导。为了研究副作用,开展了一项研究,比较CF患者每次雾化吸入硫酸多黏菌素和甲磺酸盐多黏菌素的耐受性。
9名长期感染铜绿假单胞菌的CF患者参与了一项双盲、随机交叉研究。在两次门诊就诊时,患者分别接受雾化吸入硫酸多黏菌素或甲磺酸盐多黏菌素溶液。在雾化前以及雾化后15分钟和30分钟立即进行肺功能测试。
与雾化吸入甲磺酸盐多黏菌素相比,雾化吸入硫酸多黏菌素导致肺功能平均下降幅度明显更大。与基线相比,雾化吸入硫酸多黏菌素后30分钟时FEV1以及15分钟和30分钟时FVC的平均变化(标准差)分别显著下降-7.3%(8.6%)、-5.7%(7.3%)和-8.4%(7.5%),而雾化吸入甲磺酸盐多黏菌素时则未出现这种情况(P<0.05)。7名患者因咽喉刺激和剧烈咳嗽而无法完成硫酸多黏菌素的雾化吸入。
基于这些结果得出结论,雾化吸入硫酸多黏菌素不适合用于治疗长期感染铜绿假单胞菌的CF患者。甲磺酸盐多黏菌素是雾化吸入多黏菌素的首选药物。