Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis
Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis
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DOI：
10.1038/s41598-019-38984-y
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发表时间：
2019-02-22
影响因子：
4.6
通讯作者：
Crandall, Keith A.
中科院分区：
文献类型：
--
作者：
Hahn, Andrea;Fanous, Hani;Crandall, Keith A.
在囊性纤维化（CF）患者中，气道微生物多样性降低与肺功能降低相关。关于短期抗生素治疗急性肺疾病加重的影响，存在明确的数据。然而，抗生素暴露的差异是否会影响气道微生物组的变化尚未研究。我们假设，通过静脉（IV）抗生素给药后的药代动力学和药效学（PK/PD）确定的亚治疗β-内酰胺抗生素暴露与CF气道微生物多样性的不同变化模式相关。合格儿童在健康时入组;在肺部急性加重时进行研究评估。血浆药物浓度和细菌最低抑菌浓度（MIC）用于确定治疗与亚治疗β-内酰胺抗生素暴露。从儿童中收集呼吸道样本，并提取细菌DNA扩增165 rRNA基因的V4区域。20名儿童在研究期间经历了31次APE; 45%（n = 14）的抗生素疗程被认为是治疗性的。与基线相比，治疗组患者在治疗结束时和恢复后的α多样性降低比亚治疗组更显著。治疗性和亚治疗性β-内酰胺使用与抗生素给药后CF气道微生物多样性的不同变化模式相关。
In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. Eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. Plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 165 rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. Therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration.