Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study.
Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study.
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DOI：
10.1186/s13073-021-00960-5
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发表时间：
2021-09-13
期刊：
影响因子：
12.3
通讯作者：
Egli A
中科院分区：
文献类型：
--
作者：
Cuénod A;Wüthrich D;Seth-Smith HMB;Ott C;Gehringer C;Foucault F;Mouchet R;Kassim A;Revathi G;Vogt DR;von Felten S;Bassetti S;Tschudin-Sutter S;Hettich T;Schlotterbeck G;Homberger C;Casanova C;Moran-Gilad J;Sagi O;Rodríguez-Sánchez B;Müller F;Aerni M;Gaia V;van Dessel H;Kampinga GA;Müller C;Daubenberger C;Pflüger V;Egli A
克雷伯氏菌是可导致严重感染的机会性病原体，往往具有多重耐药性，是医院获得性感染的常见原因。最近已经描述了多个新的克雷伯氏菌种，但它们的临床影响和抗生素耐药谱在很大程度上是未知的。我们的目标是探索克雷伯氏菌群和物种特异性的临床影响、抗菌素耐药性(AMR)和毒力。我们分析了克雷伯氏菌不同选择的全基因组序列数据。分离并鉴定了抗性和毒力因子。利用3594株克雷伯氏菌的基因组，我们预测了56个核糖体亚基蛋白的质量，并确定了物种特异性的标记质量。然后，我们重新分析了四个国家的八家医疗机构常规获取的22,000多个基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱图，以寻找这些物种特异性标记。使用广义线性混合效应模型对957名克雷伯氏菌感染患者的临床和微生物终点进行了分析。我们的比较基因组分析显示了附属基因组组成的群体和物种特有的趋势。鉴定出肺炎克雷伯菌(71.2%；n=12,523)、拟肺炎克雷伯菌(3.3%；n=575)、变种克雷伯氏菌(9.8%；n=1717)、拟变种克雷伯氏菌(0.3%；n=52)、催产克雷伯氏菌(8.2%；n=1445)、密歇根克雷伯氏菌(4.8%；n=836)、格氏克雷伯氏菌(2.4%；n=52)。N=425)和K.huaxensis(0.1%；n=12)。与肺炎克雷伯菌组(包括肺炎克雷伯菌、拟肺炎克雷伯菌、百变克雷伯菌和拟狂犬病克雷伯菌)相比，属于催产克雷伯氏菌群的菌株对第四代头孢菌素的耐药性较少(优势比=0.17p<；0.001，95%可信区间[0.09，0.28])。在肺炎克雷伯菌组中，被鉴定为肺炎克雷伯菌的菌株比花斑克雷伯菌对第四代头孢菌素的耐药性更高(优势比=2.61，p=0.003，95%可信区间[1.38，5.06])。与肺炎克雷伯菌组分离株相比，催产克雷伯氏菌组分离株更有可能侵袭性感染到主要无菌部位(优势比=2.39，p=0.0044，95%可信区间[1.05，5.53])。目前误诊为克雷伯氏菌。对于MALDI-TOF女士，可以使用基于核糖体标记的方法来区分克雷伯氏菌。不同的克雷伯氏菌群体和物种在AMR谱及其与侵袭性感染的联系方面存在差异，这突显了物种识别的重要性，以便能够进行有效的治疗选择。网上版载有补充材料，可在10.1186/s13073-021-00960-5查阅。
Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence. We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models. Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), “K. quasivariicola” (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and “K. quasivariicola” (odds ratio = 0.17, p < 0.001, 95% confidence interval [0.09,0.28]). Within the K. pneumoniae group, isolates identified as K. pneumoniae were more often resistant to 4th-generation cephalosporins than K. variicola isolates (odds ratio = 2.61, p = 0.003, 95% confidence interval [1.38,5.06]). K. oxytoca group isolates were found to be more likely associated with invasive infection to primary sterile sites than K. pneumoniae group isolates (odds ratio = 2.39, p = 0.0044, 95% confidence interval [1.05,5.53]). Currently misdiagnosed Klebsiella spp. can be distinguished using a ribosomal marker-based approach for MALDI-TOF MS. Klebsiella groups and species differed in AMR profiles, and in their association with invasive infection, highlighting the importance for species identification to enable effective treatment options. The online version contains supplementary material available at 10.1186/s13073-021-00960-5.
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DOI：
10.1093/cid/cix270
发表时间：
2017-07-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Gorrie CL;Mirceta M;Wick RR;Edwards DJ;Thomson NR;Strugnell RA;Pratt NF;Garlick JS;Watson KM;Pilcher DV;McGloughlin SA;Spelman DW;Jenney AWJ;Holt KE
通讯作者：
Holt KE
DOI：
10.1073/pnas.2003407117
发表时间：
2020-10-06
影响因子：
11.1
作者：
David S;Cohen V;Reuter S;Sheppard AE;Giani T;Parkhill J;European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working Group;ESCMID Study Group for Epidemiological Markers (ESGEM);Rossolini GM;Feil EJ;Grundmann H;Aanensen DM
通讯作者：
Aanensen DM
影响因子：
4.8
作者：
Long SW;Linson SE;Ojeda Saavedra M;Cantu C;Davis JJ;Brettin T;Olsen RJ
通讯作者：
Olsen RJ
影响因子：
4.9
作者：
Leitner, Eva;Zarfel, Gernot;Zollner-Schwetz, Ines
通讯作者：
Zollner-Schwetz, Ines
影响因子：
9.4
作者：
Herzog, Kathrin A. T.;Schneditz, Georg;Hoegenauer, Christoph
通讯作者：
Hoegenauer, Christoph