The approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect the susceptibility profiles of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients. This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic P. aeruginosa infection. Sputum cultures were collected annually (2011 to 2016). The primary study endpoint was the proportion of subjects whose least susceptible P. aeruginosa isolate had an aztreonam MIC that was >8 μg/ml (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and percent of predicted forced expiratory volume in 1 s (FEV₁% predicted) were obtained from the CF Foundation Patient Registry and compared between subjects meeting and those not meeting the primary endpoint. A total of 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13 to 22%) met the primary endpoint each year, and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual declines in lung function were comparable for subjects meeting and those not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it. The aztreonam susceptibility of P. aeruginosa remained consistent during the 5-year study. The relationship between P. aeruginosa isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with an accelerated decline in lung function but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01375036.)

中文翻译：

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在批准吸入氨曲南赖氨酸后，囊性纤维化患者的铜绿假单胞菌易感性模式和相关临床结果

氨曲南赖氨酸被批准用于吸入溶液 (AZLI) 引起了人们的担忧，即额外的抗生素暴露可能会影响来自囊性纤维化 (CF) 患者的铜绿假单胞菌分离株的易感性特征。这项为期 5 年的前瞻性观察性研究追踪了美国慢性铜绿假单胞菌感染CF 患者的易感性变化和临床结果。每年（2011 年至 2016 年）收集痰培养物。主要研究终点是最易感染铜绿假单胞菌的受试者比例分离株的氨曲南 MIC > 8 μg/ml（肠外断点），与前一年最不敏感的分离株相比增加了≥4 倍。肺加重、住院和 1 秒内预测用力呼气量百分比 (FEV ₁% 预测）从 CF 基金会患者登记处获得，并在满足主要终点的受试者和未达到主要终点的受试者之间进行比较。共招募了 510 名受试者；334 (65%) 人完成了研究。每年都有一致比例的可评估受试者（13% 至 22%）达到主要终点，并且在前 12 个月内使用 AZLI 与达到主要终点无关。虽然达到主要终点的受试者和未达到主要终点的受试者肺功能的年度下降相当，但达到主要终点的受试者经历了更多的肺部恶化和住院治疗。在为期 5 年的研究中，铜绿假单胞菌对氨曲南的敏感性保持一致。铜绿假单胞菌的关系分离敏感性和临床结果是复杂的；易感性降低与肺功能加速下降无关，但与更多的急性加重和住院有关，这可能反映了总体抗生素暴露增加。（本研究已在 ClinicalTrials.gov 注册，标识符为 NCT01375036。）