Transmission dynamics and between-species interactions of multidrug-resistant Enterobacteriaceae
Transmission dynamics and between-species interactions of multidrug-resistant Enterobacteriaceae
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DOI：
10.1101/436006
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发表时间：
2018-10
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通讯作者：
Thomas Crellen;P. Turner;Sreymom Pol;S. Baker;T. Nguyen;N. Stoesser;N. Day;B. Cooper
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文献类型：
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作者：
Thomas Crellen;P. Turner;Sreymom Pol;S. Baker;T. Nguyen;N. Stoesser;N. Day;B. Cooper
对抗生素的广泛耐药性是对现代医学的最严重威胁之一，世界卫生组织已将控制耐多药肠杆菌科的传播列为优先事项。减少医院病房内传播的干预措施可以通过改变患者水平的定植风险因素来了解，但对影响患者感染风险的因素的了解有限。我们使用贝叶斯分层模型分析了柬埔寨新生儿重症监护室为期一年的前瞻性携带研究数据，以估计获得多药耐药微生物的每日概率，同时考虑患者水平的时变协变量，包括物种之间的相互作用和传播事件的间隔删失。我们估计第三代头孢菌素耐药（3GC-R）肺炎克雷伯菌定植的基线日概率为0.142（95%可信区间[CrI] 0.066，0.27），几乎是获得3GC-R大肠埃希菌的日概率（0.016 [95% CrI 0.0038，0.049]）的10倍。既往定植3GC-R K。肺炎与患者获得3GC-RE的风险大大增加相关。大肠埃希菌（OR 6.4 [95%CrI 2.8，20.9]）。母乳喂养与3GC-R K定植风险降低相关。肺炎克雷伯氏菌（OR 0.73 [95%CrI 0.38，1.5]）和大肠杆菌。大肠杆菌（OR 0.62 [95%CrI 0.28，1.6]）。使用口服益生菌（嗜酸乳杆菌）没有显示出明确的证据，防止定植与3GC-R K。肺炎克雷伯菌（OR 0.83 [95%CrI 0.51，1.3]）或3GC-RE。大肠杆菌（OR 1.3 [95%CrI 0.77，2.1]）。在过去48小时内使用抗生素对获得3GC-R K的风险没有强烈影响。肺炎。对于3GC-RE.头孢曲松增加感染风险的作用最强（OR 2.2 [95% CrI 0.66，6.2]），亚胺培南降低感染风险（OR 0.31 [95% CrI 0.099，0.76]）。利用317个K.肺炎，我们确定了肺炎相关的集群，并使用了一系列的模型来推断传播率。模型比较强烈支持具有随时间变化的感染力术语的模型，该术语随定植患者的数量成比例增加，提供了患者间传播的证据，包括在一群准肺炎克雷伯氏菌中。我们的研究结果为K.肺炎可在病房内人与人之间传播。随后在患者中进行水平基因转移。pneumoniae为3GC-R K定殖之间的强相关性提供了最简洁的解释。pneumoniae和3GC-R E.杆菌
Widespread resistance to antibiotics is among the gravest threats to modern medicine, and controlling the spread of multi-drug resistant Enterobacteriaceae has been given priority status by the World Health Organization. Interventions to reduce transmission within hospital wards may be informed by modifiable patient-level risk factors for becoming colonised, however understanding of factors that influence a patient’s risk of acquisition is limited. We analyse data from a one year prospective carriage study in a neonatal intensive care unit in Cambodia using Bayesian hierarchical models to estimate the daily probability of acquiring multi-drug resistant organisms, while accounting for patient-level time-varying covariates, including interactions between species, and interval-censoring of transmission events. We estimate the baseline daily probability for becoming colonised with third generation cephalosporin resistant (3GC-R) Klebsiella pneumoniae as 0.142 (95% credible interval [CrI] 0.066, 0.27), nearly ten times higher than the daily probability of acquiring 3GC-R Escherichia coli (0.016 [95% CrI 0.0038, 0.049]). Prior colonization with 3GC-R K. pneumoniae was associated with a greatly increased risk of a patient acquiring 3GC-R E. coli (odds ratio [OR] 6.4 [95% CrI 2.8, 20.9]). Breast feeding was associated with a reduced risk of colonization with both 3GC-R K. pneumoniae (OR 0.73 [95% CrI 0.38, 1.5]) and E. coli (OR 0.62 [95% CrI 0.28, 1.6]). The use of an oral probiotic (Lactobacillus acidophilus) did not show clear evidence of protection against colonization with either 3GC-R K. pneumoniae (OR 0.83 [95% CrI 0.51, 1.3]) or 3GC-R E. coli (OR 1.3 [95% CrI 0.77, 2.1]). Antibiotic consumption within the past 48 hours did not strongly influence the risk of acquiring 3GC-R K. pneumoniae. For 3GC-R E. coli, ceftriaxone showed the strongest effect for increasing the risk of acquisition (OR 2.2 [95% CrI 0.66, 6.2]) and imipenem was associated with a decreased risk (OR 0.31 [95% CrI 0.099, 0.76). Using 317 whole-genome assemblies of K. pneumoniae, we determined putatively related clusters and used a range of models to infer transmission rates. Model comparison strongly favored models with a time-varying force of infection term that increased in proportion with the number of colonized patients, providing evidence of patient-to-patient transmission, including among a cluster of Klebsiella quasipneumoniae. Our findings provide support for the hypothesis that K. pneumoniae can be spread person-to-person within ward settings. Subsequent horizontal gene transfer within patients from K. pneumoniae provides the most parsimonious explanation for the strong association between colonization with 3GC-R K. pneumoniae and acquisition of 3GC-R E. coli.