What caused the outbreak of ESBL-producing Klebsiella pneumoniae in a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing
What caused the outbreak of ESBL-producing Klebsiella pneumoniae in a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing
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DOI：
10.1136/bmjopen-2014-007397
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发表时间：
2015-01-01
期刊：
影响因子：
2.9
通讯作者：
Nuebel, Ulrich
中科院分区：
文献类型：
--
作者：
Haller, Sebastian;Eller, Christoph;Nuebel, Ulrich
目的：我们的目的是回顾性重建的传播事件和途径的时间，以了解为什么广泛的预防措施和调查是不足以防止新的cases.Methods：我们提取了现有的信息，从病人的图表来描述的情况下，并将其与正常人群的病房。我们进行了一项队列研究，以确定病原体获得的风险因素。结果：共检出肺炎克雷伯菌37株，其中产超广谱β-内酰胺酶（ESBL）的肺炎克雷伯菌10株。肺炎血流感染。描述性流行病学表明，人与人之间的持续传播是最有可能的。队列研究的结果显示，“频繁操作”（医疗程序暴露增加的代表）与病例显著相关（RR 1.44，95% CI 1.02至2.19）。基因组序列显示，所有48个细菌分离株测序31例密切相关（最大遗传距离，12个单核苷酸多态性）。根据进化速率和序列多样性的计算，我们估计该暴发菌株自2008年以来是地方性的。结论：流行病学和系统发育分析一致表明，在微生物筛查开始之前，还有额外的未发现病例，病原体的传播在几年内仍未被发现，主要是由人与人之间的传播驱动的。全基因组测序提供了关于暴发的开始、过程和规模以及可能的传播方式的宝贵信息。
Objective: We aimed to retrospectively reconstruct the timing of transmission events and pathways in order to understand why extensive preventive measures and investigations were not sufficient to prevent new cases.Methods: We extracted available information from patient charts to describe cases and to compare them to the normal population of the ward. We conducted a cohort study to identify risk factors for pathogen acquisition. We sequenced the available isolates to determine the phylogenetic relatedness of Klebsiella pneumoniae isolates on the basis of their genome sequences.Results: The investigation comprises 37 cases and the 10 cases with ESBL (extended-spectrum beta-lactamase)-producing K. pneumoniae bloodstream infection. Descriptive epidemiology indicated that a continuous transmission from person to person was most likely. Results from the cohort study showed that 'frequent manipulation' (a proxy for increased exposure to medical procedures) was significantly associated with being a case (RR 1.44, 95% CI 1.02 to 2.19). Genome sequences revealed that all 48 bacterial isolates available for sequencing from 31 cases were closely related (maximum genetic distance, 12 single nucleotide polymorphisms). Based on our calculation of evolutionary rate and sequence diversity, we estimate that the outbreak strain was endemic since 2008.Conclusions: Epidemiological and phylogenetic analyses consistently indicated that there were additional, undiscovered cases prior to the onset of microbiological screening and that the spread of the pathogen remained undetected over several years, driven predominantly by person-to-person transmission. Whole-genome sequencing provided valuable information on the onset, course and size of the outbreak, and on possible ways of transmission.