Division of Pulmonary and Sleep Medicine and.
Biostatistics, Epidemiology, and Analytics in Research, Seattle Children's Research Institute, Seattle, Washington.
Ann Am Thorac Soc. 2022 Aug;19(8):1320-1327. doi: 10.1513/AnnalsATS.202111-1294OC.
Antibiotic selection for pulmonary exacerbation (PEx) management in children with cystic fibrosis is typically guided by prior respiratory culture results. Although antipseudomonal antibiotics are often used in children with chronic (Pa) airway infection, no data exist to guide antibiotic selection in children who are culture negative for Pa for ≥1 year. To determine among children classified as 1, 2, or 3 years' Pa negative if PEx treatment with at least one oral and/or intravenous antipseudomonal antibiotic is associated with improved clinical outcomes compared with treatment with antibiotics not effective against Pa. A retrospective cohort study was conducted using the linked Cystic Fibrosis Foundation Patient Registry-Pediatric Health Information System database. We included children 6-21 years old hospitalized between 2008 and 2018 consistently culture negative for Pa 1 year before a study PEx. Children were classified as 1 or 2 years' Pa negative if their last Pa-positive culture occurred in the 13-24 months or 25-36 months before a study PEx, respectively, with all subsequent cultures negative for Pa. Children classified as 3 years' Pa negative had no Pa-positive cultures in the 36 months before a study PEx. Inverse probability of treatment weighted linear or logistic regression models were used to compare clinical outcomes (pre- to post-PEx forced expiratory volume in 1 s, odds of returning to ≥90% of baseline lung function, and odds of having a future PEx) between antipseudomonal and non-antipseudomonal antibiotic strategies. Among all children included in the linked data set, 1,290 children with 2,347 PExs were eligible for analysis. Among all study PExs, 530, 326, and 1,491 were classified as 1, 2, and 3 years' Pa negative, respectively, and antipseudomonal antibiotics were administered in 79%, 67%, and 66% of all PExs classified as 1, 2, and 3 years' Pa negative, respectively. For all Pa-negative groups, when compared with non-antipseudomonal antibiotic regimens, antipseudomonal antibiotic treatment was not associated with greater improvement in any studied clinical outcome. Despite their common use, including antibiotics effective against Pa may provide no additional benefit for PEx treatment among children who are Pa negative for at least 1 year prior. Prospective trials are warranted to directly test this hypothesis.
在囊性纤维化患儿中，抗生素的选择通常根据先前的呼吸道培养结果进行指导。虽然针对慢性（Pa）气道感染的患儿常使用抗假单胞菌抗生素，但对于 Pa 培养阴性持续≥1 年的患儿，目前尚无指导抗生素选择的相关数据。本研究旨在明确对于 Pa 培养阴性持续 1、2 或 3 年的患儿，与使用针对 Pa 无效的抗生素相比，使用至少一种口服和/或静脉用抗假单胞菌抗生素治疗是否可改善临床结局。本研究采用回顾性队列研究，使用链接的囊性纤维化基金会患者登记-儿科健康信息系统数据库。我们纳入了 2008 年至 2018 年间，在研究性肺外展（PEx）前持续 Pa 培养阴性持续 1 年的 6-21 岁患儿。患儿被分类为 1 年或 2 年 Pa 阴性，如果他们最后一次 Pa 阳性培养发生在前一次研究性 PEx 的前 13-24 个月或前 25-36 个月，所有后续 Pa 培养均为阴性。分类为 3 年 Pa 阴性的患儿在前一次研究性 PEx 的前 36 个月内没有 Pa 阳性培养。使用逆概率治疗加权线性或逻辑回归模型比较了抗假单胞菌和非抗假单胞菌抗生素策略之间的临床结局（PEx 前至后用力呼气量 1 秒，回归至≥基线肺功能 90%的几率，以及发生未来 PEx 的几率）。在纳入的全部数据集患儿中，2347 次 PEx 中有 1290 次符合分析条件。在所有研究性 PEx 中，530、326 和 1491 次分别被分类为 1 年、2 年和 3 年 Pa 阴性，分别有 79%、67%和 66%的所有被分类为 1 年、2 年和 3 年 Pa 阴性的 PEx 使用了抗假单胞菌抗生素。对于所有 Pa 阴性组，与非抗假单胞菌抗生素方案相比，抗假单胞菌抗生素治疗并未显著改善任何研究终点的临床结局。尽管广泛使用，但对于 Pa 培养阴性持续至少 1 年的患儿，使用针对 Pa 的抗生素可能并不能带来额外的益处。需要进行前瞻性试验来直接检验这一假设。
