背景:在医院环境中,产生碳青霉烯酶的铜绿假单胞菌(CPPA)可能导致致命的患者感染。然而,CPPA的传播途径往往是未知的。因此,本病例研究旨在追踪CPPAST357的起源,该疾病在2023年导致一名因格林-巴利综合征而被遣返的危重病人发生医院获得性肺炎.
方法:通过圆盘扩散测定30种单一和联合治疗的CPPA分离株的抗菌敏感性,Etest或肉汤微量稀释。对荷兰CPPA监测计划中收到的三例CPPA分离株(一名患者和两个接收器)和四个不同的CPPAST357患者分离株进行了全基因组测序。此外,通过三个基因组库收集193个国际铜绿假单胞菌ST357组件,并使用全基因组多位点序列分型结合抗微生物耐药性基因(ARG)表征进行分析。
结果:一名携带NDM-1产生CPPA的荷兰患者从肯尼亚转移到荷兰,随后在入院后一个月内将CPPA分离株传播到当地的汇。CPPA病例分离株呈现广泛耐药表型,仅对粘菌素和头孢地洛-磷霉素敏感。系统发育分析显示,来自亚洲(n=92)的ST357分离株的等位基因距离(平均值=150,最大值=527等位基因)存在相当大的差异,欧洲(n=58),非洲(n=21),美国(n=16),大洋洲(n=2)和未注册区域(n=4)。然而,病例分离株(n=3)和其他荷兰患者监测计划分离株(n=2)位于肯尼亚分离株的亚分支中(n=17;不同的15-49个等位基因),美国(n=7;21-115个等位基因)和其他国家(n=6;14-121个等位基因)。这与先前在肯尼亚住院的2/3荷兰患者一致。此外,超过一半的分离株(20/35)在这个子进化枝与9/17肯尼亚,5/5荷兰语,4/7美国和2/6其他国家,其特征在于blaNDM-1,aph(3')-VI,ARR-3和cmlA1ARGs。
结论:本研究提出了一种广泛耐药的产生NDM的铜绿假单胞菌ST357的亚克隆,具有独特的耐药性,该耐药性是通过将来自肯尼亚的重症患者遣返而引入荷兰的。因此,建议对遣返患者进行CPPA监测,同时警惕环境污染风险,以发现并防止进一步传播。
BACKGROUND: In the hospital environment, carbapenemase-producing Pseudomonas aeruginosa (CPPA) may lead to fatal patient infections. However, the transmission routes of CPPA often remain unknown. Therefore, this case study aimed to trace the origin of CPPA ST357, which caused a hospital-acquired pneumonia in a repatriated critically ill patient suffering from Guillain-Barré Syndrome in 2023.
METHODS: Antimicrobial susceptibility of the CPPA isolate for 30 single and combination therapies was determined by disk-diffusion, Etest or broth microdilution. Whole-genome sequencing was performed for three case CPPA isolates (one patient and two sinks) and four distinct CPPA ST357 patient isolates received in the Dutch CPPA surveillance program. Furthermore, 193 international P. aeruginosa ST357 assemblies were collected via three genome repositories and analyzed using whole-genome multi-locus sequence typing in combination with antimicrobial resistance gene (ARG) characterization.
RESULTS: A Dutch patient who carried NDM-1-producing CPPA was transferred from Kenya to the Netherlands, with subsequent dissemination of CPPA isolates to the local sinks within a month after admission. The CPPA case isolates presented an extensively drug-resistant phenotype, with susceptibility only for colistin and cefiderocol-fosfomycin. Phylogenetic analysis showed considerable variation in allelic distances (mean = 150, max = 527 alleles) among the ST357 isolates from Asia (n = 92), Europe (n = 58), Africa (n = 21), America (n = 16), Oceania (n = 2) and unregistered regions (n = 4). However, the case isolates (n = 3) and additional Dutch patient surveillance program isolates (n = 2) were located in a sub-clade of isolates from Kenya (n = 17; varying 15-49 alleles), the United States (n = 7; 21-115 alleles) and other countries (n = 6; 14-121 alleles). This was consistent with previous hospitalization in Kenya of 2/3 Dutch patients. Additionally, over half of the isolates (20/35) in this sub-clade presented an identical resistome with 9/17 Kenyan, 5/5 Dutch, 4/7 United States and 2/6 other countries, which were characterized by the blaNDM-1, aph(3\')-VI, ARR-3 and cmlA1 ARGs.
CONCLUSIONS: This study presents an extensively-drug resistant subclone of NDM-producing P. aeruginosa ST357 with a unique resistome which was introduced to the Netherlands via
repatriation of critically ill patients from Kenya. Therefore, the monitoring of repatriated patients for CPPA in conjunction with vigilance for the risk of environmental contamination is advisable to detect and prevent further dissemination.