Division of Pulmonary, Allergy and Critical Care, Columbia University Irving Medical Center, New York, New York, USA
Division of Pulmonary and Critical Care, Maine Medical Center, Portland, Maine, USA.
Antimicrob Agents Chemother. 2021 Feb 17;65(3). doi: 10.1128/AAC.02327-20.
The approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect the susceptibility profiles of 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 infection. Sputum cultures were collected annually (2011 to 2016). The primary study endpoint was the proportion of subjects whose least susceptible 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 (FEV% 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 remained consistent during the 5-year study. The relationship between 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.).
注射用氨曲南赖氨酸（AZLI）获得批准后，人们担心这会增加抗生素的使用，从而可能影响囊性纤维化（CF）患者分离株的药敏谱。这项为期 5 年的前瞻性观察性研究，在美国对患有慢性感染的 CF 患者进行了跟踪监测，以评估其药敏变化和临床结局。每年收集一次痰培养（2011 年至 2016 年）。主要研究终点是与上一年相比，至少有 1 例分离株对氨曲南的 MIC 值（>8μg/ml，即注射用药物的折点）增加≥4 倍，且最不敏感的分离株对氨曲南的 MIC 值>8μg/ml（即注射用药物的折点）的患者比例。从 CF 基金会患者登记处获得每年因肺部恶化、住院和预测用力呼气量百分比（FEV%预测）的年度数据，并将其与达到和未达到主要终点的患者进行比较。共纳入 510 例患者，其中 334 例（65%）完成了研究。每年都有一定比例（13%至 22%）的可评估患者符合主要终点，且在前 12 个月内使用 AZLI 与达到主要终点无关。虽然达到和未达到主要终点的患者的肺功能年下降率相当，但达到主要终点的患者发生更多的肺部恶化和住院治疗。在 5 年的研究期间，对氨曲南的敏感性保持一致。分离株的药敏性与临床结局之间的关系较为复杂；敏感性降低与肺功能加速下降无关，但与更多恶化和住院治疗有关，这可能反映出总体抗生素暴露的增加。（本研究已在 ClinicalTrials.gov 注册，登记号为 NCT01375036.）。
