Objectives

Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213–26].

Methods

Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied.

Results

Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13–1.40) versus 0.54 (95% CI 0.89–0.19) log₁₀ CFU/g for placebo (second period) to 2.07 (95% CI 2.45–1.69) versus 0.70 (95% CI 1.11–0.29) log₁₀ CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC₅₀ increased from 0.5 to 1 mg/L, MIC₉₀ increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected.

Conclusion

Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.

中文翻译：

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在患有非囊性纤维化支气管扩张和慢性铜绿假单胞菌肺部感染的个体中，吸入脂质体环丙沙星治疗48周后观察到微生物学变化

目标

铜绿假单胞菌的非囊性纤维化支气管扩张（NCFBE）与肺部加重（PEx）和死亡风险增加有关。欧洲呼吸学会指南有条件地建议对NCFBE，铜绿假单胞菌和每年3次或以上PEx的人吸入抗菌药物。我们报告了ARD-3150（吸入脂质体环丙沙星）在患有铜绿假单胞菌和PEx病史的NCFBE患者中进行的两项随机，为期48周的安慰剂对照试验的微生物学结果[Lancet Respir Med 2019; 7：213–26]。

方法

分析了582位参与者的呼吸分泌物，这些参与者接受了多达六个28天的开/关治疗周期，以分析其痰液中的铜绿假单胞菌，肺炎链球菌，流感嗜血杆菌，卡他莫拉菌，金黄色葡萄球菌和大肠杆菌密度，铜绿假单胞菌对其他细菌的敏感性抗菌药物以及其他细菌机会主义者的患病率。研究了PEx风险与痰液密度，抗菌药敏感性和机会主义患病率变化之间的关系。

结果

痰铜绿假单胞菌从基线降低密度ARD-3150治疗后的范围为1.77（95％CI 2.13-1.40）与0.54（95％CI 0.89-0.19）日志₁₀  CFU /克为安慰剂（第2期间），以2.07（95％ 安慰剂（第四期）的CI为0.45-1.69）与0.70（95％CI为1.11-0.29）对数为₁₀ CFU / g，密度降低幅度与PEx获益之间只有适度的相关性。ARD-3150（但非安慰剂）治疗与铜绿假单胞菌环丙沙星MIC升高有关，但在整个研究过程中未出现其他细菌机会主义者。环丙沙星MIC ₅₀从0.5增至1 mg / L，MIC ₉₀从4增至16 mg / L。其他抗微生物MIC大多未受影响。

结论

在ARD-3150治疗的48周内，微生物学变化似乎不大。观察到环丙沙星药敏性降低（但其他抗生素药敏性未降低），但这似乎并不排除降低PEx风险的益处。