Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland OH, USA.
CFF Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
J Cyst Fibros. 2021 Mar;20(2):257-263. doi: 10.1016/j.jcf.2020.05.008. Epub 2020 Jun 4.
Background Antimicrobial susceptibility testing (AST) of bacterial isolates is a time- and resource-intensive procedure recommended by cystic fibrosis (CF) treatment guidelines for antimicrobial selection for pulmonary exacerbation (PEx) treatment. Methods We studied relationships between Pseudomonas aeruginosa (Pa) isolate AST results, antipseudomonal PEx treatments, and treatment responses as change in weight and percent predicted forced expiratory volume in 1 s (ppFEV) as well as future antimicrobial treatment hazard for PEx occurring at a CF care center from 1999 through 2018. Treatments were categorized by "Pa coverage" as complete (all Pa isolates susceptible by AST to at least one administered agent), none (no isolates susceptible), incomplete (some, but not all isolates susceptible), and indeterminant (administered antipseudomonals not evaluated by AST). Weight and ppFEV responses were compared across Pa coverage categories using unadjusted and adjusted general estimating equations; hazard of future treatment was assessed by Cox and logistic regression. Results Among 3820 antimicrobial PEx treatment events in 413 patients with Pa, 62.6% (2390) had complete Pa coverage; 8.9% (340), 2.4% (99), and 26.2% (1000), had no, incomplete, and indeterminant Pa coverage, respectively. Mean baseline to follow-up weight change was +0.74 kg [95% CI 0.63, 0.86]; ppFEV change was +1.60 [1.29, 1.90]. Pa coverage category was not associated with significant differences in weight or ppFEV change or with future antimicrobial treatment hazard. Conclusions We did not observe superior responses for AST-defined complete Pa coverage treatments versus lesser coverage treatments, suggesting that AST may be of little utility in choosing antimicrobials for CF PEx treatment.
抗微生物药物敏感性测试（AST）是一种耗时且资源密集型的程序，囊性纤维化（CF）治疗指南推荐用于选择肺加重（PEx）治疗的抗微生物药物。
我们研究了铜绿假单胞菌（Pa）分离株 AST 结果、抗假单胞菌 PEx 治疗以及治疗反应（体重变化和预计用力呼气量的百分比（ppFEV）变化）之间的关系，以及未来 CF 护理中心发生 PEx 的抗微生物治疗风险，研究时间为 1999 年至 2018 年。治疗方法根据“Pa 覆盖”进行分类，包括完全（AST 显示所有 Pa 分离株对至少一种给予的药物敏感）、无（无分离株敏感）、不完全（一些，但不是所有分离株敏感）和不确定（AST 未评估给予的抗假单胞菌药物）。使用未调整和调整后的一般估计方程比较 Pa 覆盖类别之间的体重和 ppFEV 反应；未来治疗的风险通过 Cox 和逻辑回归评估。
在 413 例 Pa 患者的 3820 例抗微生物 PEx 治疗事件中，62.6%（2390 例）有完全的 Pa 覆盖；8.9%（340 例）、2.4%（99 例）和 26.2%（1000 例）分别为无、不完全和不确定的 Pa 覆盖。平均基线到随访的体重变化为+0.74kg[95%置信区间 0.63，0.86]；ppFEV 变化为+1.60[1.29，1.90]。Pa 覆盖类别与体重或 ppFEV 变化或未来抗微生物治疗风险无显著差异。
我们没有观察到 AST 定义的完全 Pa 覆盖治疗与较少覆盖治疗相比具有更好的反应，这表明 AST 对抗微生物药物选择可能对 CF PEx 治疗没有太大用处。
