Baylor College of Medicine, Texas Children's Hospital Pediatric Pulmonary Medicine, 6621 Fannin, Suite 1040.12, Houston, TX 77030-2399, USA.
J Antimicrob Chemother. 2011 Oct;66(10):2398-404. doi: 10.1093/jac/dkr303. Epub 2011 Jul 22.
Aztreonam for inhalation solution (AZLI) is an inhaled antibiotic for patients with cystic fibrosis (CF) and Pseudomonas aeruginosa airway infection. The risk of selecting for P. aeruginosa isolates with reduced susceptibility to antibiotics is inherent to their use, but is of particular concern following repeated exposure and when complete eradication of lung pathogens is difficult to obtain. We investigated whether repeated treatment courses of AZLI led to decreases in P. aeruginosa susceptibility to aztreonam or other antibiotics.
Serial sputum specimens were collected and processed for isolation and quantification of all P. aeruginosa isolates in a Phase 3 open-label, 18 month study (NCT00128492) including 274 CF patients receiving up to nine courses of AZLI twice daily (AZLI2) or thrice daily (AZLI3) (28 days on/28 days off). P. aeruginosa antibiotic susceptibility testing was conducted.
No changes were observed in the aztreonam MIC(50) for all P. aeruginosa isolates collected from AZLI3 patients, while intermittent increases were observed in the aztreonam MIC(90). Approximately 70% of the P. aeruginosa isolates with the highest aztreonam MIC from each patient receiving AZLI3 remained unchanged or decreased relative to that patient's equivalent isolate at baseline; 30% experienced an increase in MIC. Few decreases in P. aeruginosa susceptibility to other antibiotics were observed in AZLI3 patients, while increases in P. aeruginosa susceptibility to tobramycin were observed.
Few decreases in aztreonam susceptibility were reported in patients receiving AZLI3. Increases in tobramycin susceptibility were observed, suggesting that novel treatment paradigms may be able to prolong antibiotic susceptibility in CF patients.
阿佐米星吸入溶液（AZLI）是一种用于囊性纤维化（CF）和铜绿假单胞菌气道感染患者的吸入性抗生素。使用抗生素会导致铜绿假单胞菌对其敏感性降低，这是固有风险，但在反复暴露后以及难以完全清除肺部病原体时，这种风险尤为令人关注。我们研究了重复使用 AZLI 是否会导致铜绿假单胞菌对阿佐米星或其他抗生素的敏感性降低。
在一项 3 期开放标签、18 个月的研究（NCT00128492）中，连续采集痰标本并进行处理，以分离和定量所有铜绿假单胞菌分离株，该研究纳入了 274 名接受多达 9 个疗程的每日两次（AZLI2）或每日三次（AZLI3）AZLI 治疗的 CF 患者（28 天用药/28 天停药）。对铜绿假单胞菌的抗生素敏感性进行了检测。
从接受 AZLI3 治疗的患者中采集的所有铜绿假单胞菌分离株的阿佐米星 MIC（50）没有变化，而阿佐米星 MIC（90）间歇性增加。大约 70%的接受 AZLI3 治疗的患者中，阿佐米星 MIC 最高的铜绿假单胞菌分离株与基线时该患者的等效分离株相比保持不变或降低，30%的分离株 MIC 增加。在接受 AZLI3 治疗的患者中，观察到铜绿假单胞菌对其他抗生素的敏感性降低的情况较少，而对妥布霉素的敏感性增加。
在接受 AZLI3 治疗的患者中，报告的阿佐米星敏感性降低的情况较少。观察到妥布霉素敏感性增加，表明新型治疗方案可能能够延长 CF 患者的抗生素敏感性。
