Loss of bacterial diversity during antibiotic treatment of intubated patients colonized with Pseudomonas aeruginosa
Loss of bacterial diversity during antibiotic treatment of intubated patients colonized with Pseudomonas aeruginosa
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DOI：
10.1128/jcm.02187-06
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发表时间：
2007-06-01
影响因子：
9.4
通讯作者：
Bristow, J.
中科院分区：
文献类型：
--
作者：
Flanagan, J. L.;Brodie, E. L.;Bristow, J.
铜绿假单胞菌所致气道感染的治疗是一项严峻的临床挑战，但对于插管患者气道感染的微生物生态学知之甚少。我们利用16S rRNA克隆文库和微阵列（系统发育芯片，PhyloChip）分析了铜绿假单胞菌定植的插管患者气管内吸出物中的细菌多样性，以确定抗生素治疗期间细菌群落组成的变化。从因择期手术短暂插管的患者所取得的吸出物中不存在细菌16S rRNA基因，但在所有长期插管患者的样本中通过聚合酶链反应（PCR）检测到该基因。对16S rRNA克隆文库进行测序表明，在铜绿假单胞菌定植的患者肺部存在许多口腔、鼻腔和胃肠道相关细菌，包括已知的病原体。系统发育芯片分析检测到了相同的生物体以及许多在克隆文库中未检测到的低丰度的其他细菌类群。对于每位患者，两种不依赖培养的方法均显示，使用抗生素后细菌多样性降低，且群落主要由肺部病原体主导。在研究的7名患者中，有6名患者体内铜绿假单胞菌成为优势菌种，尽管这6名患者中有5名使用了体外对该菌敏感的抗生素进行治疗。我们的数据表明，在抗生素选择作用下细菌多样性的丧失与铜绿假单胞菌定植的通气患者肺炎的发生高度相关。有趣的是，系统发育芯片分析表明铜绿假单胞菌和芽孢杆菌纲之间丰度呈相互变化，这表明这些菌群可能竞争相似的生态位，并提示微生物多样性的丧失可能直接导致病原体选择和持续存在的可能机制。
Management of airway infections caused by Pseudomonas aeruginosa is a serious clinical challenge, but little is known about the microbial ecology of airway infections in intubated patients. We analyzed bacterial diversity in endotracheal aspirates obtained from intubated patients colonized by P. aeruginosa by using 16S rRNA clone libraries and microarrays (PhyloChip) to determine changes in bacterial community compositions during antibiotic treatment. Bacterial 16S rRNA genes were absent from aspirates obtained from patients briefly intubated for elective surgery but were detected by PCR in samples from all patients intubated for longer periods. Sequencing of 16S rRNA clone libraries demonstrated the presence of many orally, nasally, and gastrointestinally associated bacteria, including known pathogens, in the lungs of patients colonized with P. aeruginosa. PhyloChip analysis detected the same organisms and many additional bacterial groups present at low abundance that were not detected in clone libraries. For each patient, both culture-independent methods showed that bacterial diversity decreased following the administration of antibiotics, and communities became dominated by a pulmonary pathogen. P. aeruginosa became the dominant species in six of seven patients studied, despite treatment of five of these six with antibiotics to which it was sensitive in vitro. Our data demonstrate that the loss of bacterial diversity under antibiotic selection is highly associated with the development of pneumonia in ventilated patients colonized with P. aeruginosa. Interestingly, PhyloChip analysis demonstrated reciprocal changes in abundance between P. aeruginosa and the class Bacilli, suggesting that these groups may compete for a similar ecological niche and suggesting possible mechanisms through which the loss of microbial diversity may directly contribute to pathogen selection and persistence.