PDF(Pubmed)
Abstract：
Non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP CRE) may be associated with a grave outcome. The common underlying mechanism is beta-lactamases and mutations in outer membrane porins. We report a case of a deep-seated infection caused by Klebsiella pneumoniae ST395 not amenable to source control, involving recurrent bloodstream infection, resulting in in vivo selection of carbapenem resistance under therapy. Three consecutive K. pneumoniae blood isolates were studied using short- and long-read sequencing. The genomes were subject to resistome and virulome, phylogenetic, and plasmid analyses. ompK36 porins were analyzed at the nucleotide and amino acid levels. Genomes were compared to 297 public ST395 K. pneumoniae genomes using cgMLST, resistome, and porin analyses and the EuSCAPE project. Relevant ompK36 and micF sequences were extracted and analyzed as above. The three sequential K. pneumoniae blood isolates belonged to the same clone. Subsequent CR isolates revealed a new large deletion of the ompK36 gene also involving the upstream region (deletion of micF). Comparison with public ST395 genomes revealed the study isolates belonged to clade B, representing a separate clone. N-terminal large ompK36 truncations were uncommon in both public data sets. In vivo selection of non-CP CRE K. pneumoniae could have substantial clinical implications. Such selection should be scrutinized through repeated cultures and frequent susceptibility testing during antimicrobial treatment, especially in the context of persistent or recurrent bloodstream infections and when adequate source control cannot be achieved. The occurrence of an unusually large deletion involving the ompK36 locus and upstream micF should be further studied.
摘要：
不产生碳青霉烯酶的耐碳青霉烯类肠杆菌（非CPCRE）可能与严重的后果有关。常见的潜在机制是β-内酰胺酶和外膜孔蛋白中的突变。我们报告了一例由肺炎克雷伯菌ST395引起的深部感染，不适合源控制，涉及复发性血流感染，导致体内选择碳青霉烯耐药的治疗。使用短读和长读测序研究了三个连续的肺炎克雷伯菌血液分离株。基因组受到抗性组和病毒组的影响，系统发育，和质粒分析。在核苷酸和氨基酸水平分析ompK36孔蛋白。使用cgMLST将基因组与297个公共ST395肺炎克雷伯菌基因组进行比较，抗性，以及门蛋白分析和EuSCAPE项目。如上所述提取和分析相关的ompK36和micF序列。三个连续的肺炎克雷伯菌血液分离物属于相同的克隆。随后的CR分离株揭示了ompK36基因的新的大缺失，也涉及上游区域（micF的缺失）。与公共ST395基因组的比较显示，研究分离株属于进化枝B，代表一个单独的克隆。N端大ompK36截断在两个公共数据集中都不常见。非CPCRE肺炎克雷伯菌的体内选择可能具有实质性的临床意义。在抗菌治疗期间，应通过反复培养和频繁的药敏试验来仔细检查这种选择。特别是在持续性或复发性血流感染的情况下，以及无法实现充分的源控制。应进一步研究涉及ompK36基因座和上游micF的异常大缺失的发生。
