Yao Yancheng, Imirzalioglu Can, Falgenhauer Linda, Falgenhauer Jane, Heinmüller Petra, Domann Eugen, Chakraborty Trinad
Institute of Medical Microbiology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany.
German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, 35392 Giessen, Germany.
Antibiotics (Basel). 2024 Jul 23;13(8):682. doi: 10.3390/antibiotics13080682.
The worldwide emergence and dissemination of carbapenem-resistant Gram-negative bacteria (CRGNB) is a challenging problem of antimicrobial resistance today. Outbreaks with CRGNB have severe consequences for both the affected healthcare settings as well as the patients with infection. Thus, bloodstream infections caused by metallo-ß-lactamase-producing can often have clinical implications, resulting in high mortality rates due to delays in administering effective treatment and the limited availability of treatment options. The overall threat of CRGNB is substantial because carbapenems are used to treat infections caused by ESBL-producing which also exist with high frequency within the same geographical regions. A genome-based surveillance of 589 CRGNB from 61 hospitals across the federal state Hesse in Germany was implemented using next-generation sequencing (NGS) technology to obtain a high-resolution landscape of carbapenem-resistant isolates over a three-year period (2017-2019). The study examined all reportable CRGNB isolates submitted by participating hospitals. This included isolates carrying known carbapenemases (435) together with carbapenem-resistant non-carbapenemase producers (154). Predominant carbapenemase producers included , , and . Over 80% of 375 carbapenem-resistant determinants including KPC-, NDM-, VIM- and OXA-48-like ones detected in 520 were plasmid-encoded, and half of these were dominated by a few incompatibility (Inc) types, viz., IncN, IncL/M, IncFII and IncF(). Our results revealed that plasmids play an extraordinary role in the dissemination of carbapenem resistance in the heterogeneous CRGNB population. The plasmids were also associated with several multispecies dissemination events and local outbreaks throughout the study period, indicating the substantial role of horizontal gene transfer in carbapenemase spread. Furthermore, due to vertical and horizontal plasmid transfer, this can have an impact on implant-associated infections and is therefore important for antibiotic-loaded bone cement and drug-containing devices in orthopedic surgery. Future genomic surveillance projects should increase their focus on plasmid characterization.
耐碳青霉烯类革兰氏阴性菌（CRGNB）在全球范围内的出现和传播是当今抗菌药物耐药性面临的一个具有挑战性的问题。CRGNB的暴发对受影响的医疗机构和感染患者都会产生严重后果。因此，由产金属β-内酰胺酶的细菌引起的血流感染往往具有临床意义，由于有效治疗的延迟给药和治疗选择的有限性，导致死亡率很高。CRGNB的总体威胁很大，因为碳青霉烯类药物用于治疗由产超广谱β-内酰胺酶的细菌引起的感染，而这些细菌在同一地理区域也高频存在。利用下一代测序（NGS）技术，对德国黑森州61家医院的589株CRGNB进行了基于基因组的监测，以获得三年期间（2017 - 2019年）耐碳青霉烯类分离株的高分辨率概况。该研究检查了参与医院提交的所有可报告的CRGNB分离株。这包括携带已知碳青霉烯酶的分离株（435株）以及耐碳青霉烯类非碳青霉烯酶产生菌（154株）。主要的碳青霉烯酶产生菌包括 blaKPC、blaNDM、blaVIM 和 blaOXA - 48 样酶。在520株分离株中检测到的375种耐碳青霉烯类决定簇（包括 blaKPC - 、blaNDM - 、blaVIM - 和 blaOXA - 48 样）中，超过80%是质粒编码的，其中一半由少数不相容（Inc）类型主导，即 IncN、IncL/M、IncFII 和 IncF（）。我们的结果表明，质粒在异质性CRGNB群体中耐碳青霉烯类耐药性的传播中发挥了非凡作用。在整个研究期间，这些质粒还与多个多物种传播事件和局部暴发有关，表明水平基因转移在碳青霉烯酶传播中发挥了重要作用。此外，由于质粒的垂直和水平转移，这可能会对植入相关感染产生影响，因此对于骨科手术中含抗生素的骨水泥和含药装置很重要。未来的基因组监测项目应更加关注质粒特征分析。
