Lo Stephanie W, Gladstone Rebecca A, van Tonder Andries J, Du Plessis Mignon, Cornick Jennifer E, Hawkins Paulina A, Madhi Shabir A, Nzenze Susan A, Kandasamy Rama, Ravikumar K L, Elmdaghri Naima, Kwambana-Adams Brenda, Almeida Samanta Cristine Grassi, Skoczynska Anna, Egorova Ekaterina, Titov Leonid, Saha Samir K, Paragi Metka, Everett Dean B, Antonio Martin, Klugman Keith P, Li Yuan, Metcalf Benjamin J, Beall Bernard, McGee Lesley, Breiman Robert F, Bentley Stephen D, von Gottberg Anne
Parasites and Microbes Programme, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.
J Antimicrob Chemother. 2020 Mar 1;75(3):512-520. doi: 10.1093/jac/dkz477.
We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.
We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth-death model.
We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth-death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of ∼2.5. R declined to ∼1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage.
The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era.
我们报告了肺炎链球菌中tet(S/M)的情况，并研究了其在全国临床干预措施背景下的时间传播情况。
我们在Illumina HiSeq测序仪上对来自29个国家的12254株肺炎球菌分离株进行了全基因组测序。从基因组中推断血清型、多位点序列类型（MLST）和抗生素耐药性。使用Gubbins构建单核苷酸多态性（SNP）树。使用出生-死亡模型重建时间传播情况。
我们在131株肺炎球菌分离株中鉴定出tet(S/M)，且均未携带其他已知的tet基因。对121株tet(S/M)阳性分离株进行了四环素敏感性测试，结果显示全部耐药。大部分（74%）tet(S/M)阳性分离株来自南非，且在幼儿中引起侵袭性疾病（在可获取HIV状态的病例中，59%为HIV阳性）。除两株外，所有tet(S/M)阳性分离株均属于克隆复合体（CC）230。CC230（n = 389）的全球系统发育分析表明，tet(S/M)阳性分离株形成了一个预测对青霉素、复方新诺明、红霉素和四环素耐药的亚谱系。出生-死亡模型检测到该亚谱系在2000年至2004年期间在南非出现了一次未被识别的暴发，预期继发感染数（有效繁殖数，R）约为2.5。R在2005年降至约1.0，在2012年降至<1.0。疫情下降可能与2004年抗逆转录病毒治疗可及性的改善以及2009年肺炎球菌结合疫苗（PCV）的引入有关。在该亚谱系中观察到从疫苗血清型14向非疫苗血清型23A的荚膜转换。
肺炎球菌中tet(S/M)的流行率较低，其传播是由于南非CC230的一次未被识别的暴发。该多重耐药亚谱系中的荚膜转换突出了其在PCV13时代后继续引起疾病的潜力。
