Emerg Infect Dis. 2023 Feb;29(2):341-350. doi: 10.3201/eid2902.221066.
Clonal complex 4821 (CC4821) Neisseria meningitidis, usually resistant to quinolones but susceptible to penicillin and third-generation cephalosporins, is increasing worldwide. To characterize the penicillin-nonsusceptible (Pen) meningococci, we analyzed 491 meningococci and 724 commensal Neisseria isolates in Shanghai, China, during 1965-2020. The Pen proportion increased from 0.3% in 1965-1985 to 7.0% in 2005-2014 and to 33.3% in 2015-2020. Of the 26 Pen meningococci, 11 (42.3%) belonged to the CC4821 cluster; all possessed mutations in penicillin-binding protein 2, mostly from commensal Neisseria. Genetic analyses and transformation identified potential donors of 6 penA alleles. Three Pen meningococci were resistant to cefotaxime, 2 within the CC4821 cluster. With 96% of the Pen meningococci beyond the coverage of scheduled vaccination and the cefotaxime-resistant isolates all from toddlers, quinolone-resistant CC4821 has acquired penicillin and cefotaxime resistance closely related to the internationally disseminated ceftriaxone-resistant gonococcal FC428 clone, posing a greater threat especially to young children.
克隆复合体 4821（CC4821）脑膜炎奈瑟菌通常对喹诺酮类药物耐药，但对青霉素和第三代头孢菌素敏感，在全球范围内呈上升趋势。为了对青霉素不敏感（Pen）的脑膜炎奈瑟菌进行特征分析，我们对 1965 年至 2020 年期间中国上海的 491 株脑膜炎奈瑟菌和 724 株共生奈瑟菌进行了分析。Pen 比例从 1965 年至 1985 年的 0.3%增加到 2005 年至 2014 年的 7.0%，再增加到 2015 年至 2020 年的 33.3%。在 26 株 Pen 脑膜炎奈瑟菌中，有 11 株（42.3%）属于 CC4821 群；所有菌均携带青霉素结合蛋白 2 的突变，主要来源于共生奈瑟菌。遗传分析和转化鉴定出 6 种 penA 等位基因的潜在供体。3 株 Pen 脑膜炎奈瑟菌对头孢噻肟耐药，其中 2 株属于 CC4821 群。96%的 Pen 脑膜炎奈瑟菌超出了计划疫苗接种的覆盖范围，且所有对头孢噻肟耐药的分离株均来自幼儿，携带喹诺酮耐药性的 CC4821 已获得与国际传播的头孢曲松耐药淋球菌 FC428 克隆密切相关的青霉素和头孢噻肟耐药性，对幼儿构成了更大的威胁。
