Table_2_Antimicrobial susceptibility profiles and genotyping of Neisseria meningitidis of serogroup C, Italy, 2000–2020.xlsx

BackgroundIn Italy the introduction of meningococcal C conjugate vaccine in 2005 has led to a significant reduction of invasive meningococcal disease (IMD) caused by Neisseria meningitidis of serogroup C (MenC). However, this serogroup is still responsible of sporadic cases, clusters and local outbreaks. The study aims to investigate the genotype and antimicrobial susceptibility profile of MenC isolates collected in Italy from 2000 to 2020.
MethodsBacterial isolates and biological samples (blood or cerebrospinal fluid) from invasive meningococcal cases are collected and characterized at the National Reference Laboratory for IMD of Istituto Superiore di Sanità. Antimicrobial susceptibility was determined by MIC Test Strip Method and interpreted according to the EUCAST breakpoints guideline. Genotypic characteristics, including multi locus sequence typing (MLST), finetype, and antimicrobial resistance target genes were performed and analyzed using the PubMLST database. Genomic comparison of core genome MLST (cgMLST) of MenC genomes was also carried out.
ResultsFrom 2000 to 2020, a total of 665 MenC isolates were investigated for antimicrobial susceptibility and 301 for genotyping. Over two decades, almost all MenC isolates resulted susceptible to antimicrobials with few isolates resulting resistant to ciprofloxacin (N = 2), penicillin G (N = 13), and rifampicin (N = 9), respectively. Molecular typing of MenC obtained from isolates or clinical specimens identified mostly the genotype C:P1.5-1,10-8:F3-6:ST-11(cc11). However, phylogenetic analysis, performed on genomes from MenC isolates, identified two sub lineages, 11.1 and 11.2, among cc11, of which the sub lineage 11.2 was the predominant.
ConclusionWider application of the genomic analysis and monitoring of antimicrobial susceptibility represent key aspects of IMD surveillance and to monitor the continued evolution of these hyperinvasive strains.

背景
2005年，意大利引入脑膜炎球菌C结合疫苗后，由血清群C型脑膜炎奈瑟菌（Neisseria meningitidis serogroup C，MenC）引发的侵袭性脑膜炎球菌病（invasive meningococcal disease, IMD）病例数显著下降。但该血清群仍可导致散发病例、聚集性疫情以及局部暴发。本研究旨在对2000年至2020年意大利收集的MenC分离株进行基因型与抗菌药物敏感性谱分析。
方法
本研究从侵袭性脑膜炎球菌病患者中收集细菌分离株与生物样本（血液或脑脊液），并在意大利卫生研究院（Istituto Superiore di Sanità）IMD国家参考实验室完成菌株鉴定。采用MIC试纸条法（MIC Test Strip Method）检测抗菌药物敏感性，并依据欧洲抗菌药物敏感性试验委员会（European Committee on Antimicrobial Susceptibility Testing, EUCAST）折点指南进行结果判读。利用PubMLST数据库（PubMLST database）对菌株的基因型特征进行分析，包括多位点序列分型（multi locus sequence typing, MLST）、血清分型以及抗菌药物耐药靶基因检测。此外，还对MenC基因组开展了核心基因组MLST（core genome MLST, cgMLST）基因组比较分析。
结果
2000年至2020年间，本研究共纳入665株MenC分离株进行抗菌药物敏感性检测，其中301株完成基因分型。二十余年间，几乎所有MenC分离株对各类抗菌药物均表现为敏感，仅少数分离株对环丙沙星（N=2）、青霉素G（N=13）以及利福平（N=9）耐药。从分离株或临床样本中获得的MenC分子分型结果显示，最常见的基因型为C:P1.5-1,10-8:F3-6:ST-11(cc11)。然而，对MenC分离株基因组开展的系统发育分析显示，cc11克隆群中存在两个亚谱系（11.1与11.2），其中亚谱系11.2为优势谱系。
结论
扩大基因组分析的应用范围并加强抗菌药物敏感性监测，是侵袭性脑膜炎球菌病监测工作的核心环节，也有助于持续追踪这些高侵袭性菌株的演化进程。