Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
J Antimicrob Chemother. 2019 May 1;74(5):1223-1232. doi: 10.1093/jac/dkz032.
ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates.
We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time.
Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar.
There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations.
产超广谱β-内酰胺酶（ESBL）的肺炎克雷伯菌（KPN）对全球人类健康构成重大威胁。我们进行了 WGS 研究，以了解马拉维产 ESBL 的 KPN 的遗传背景，并将其置于其他全球分离株的背景下。
我们对从马拉维布兰太尔伊丽莎白女王中央医院住院患者中分离的 72 株侵袭性和定植性 KPN 分离株进行了基因组测序。我们对这些分离株以及来自肯尼亚（n = 66）和撒哈拉以南非洲以外地区（n = 67）的先前发表的基因组进行了系统发育和种群结构分析。我们筛选了抗菌药物耐药（AMR）遗传决定因素的存在情况，并通过基因组序列簇、AMR 表型和时间进行了关联分析。
马拉维分离株符合 KPN 的全球种群结构，聚类为 KpI、KpII 和 KpIII 的主要谱系。马拉维的 KpI 分离株与肯尼亚的分离株关系更密切，两者的克隆性均高于来自世界其他地区的分离株。我们在马拉维 KPN 分离株的不同谱系中发现了多种 ESBL 基因，包括 blaCTX-M-15、几种 blaSHV、blaTEM-63 和 blaOXA-10 以及其他 AMR 基因。在马拉维的 KPN 分离株中未检测到碳青霉烯类耐药基因；然而，我们检测到了 IncFII 和 IncFIB 质粒，这些质粒与碳青霉烯类耐药相关的质粒 pNDM-mar 相似。
马拉维存在多种 ESBL 基因和可携带碳青霉烯类耐药的流行质粒。除非迅速采取适当的干预措施，否则这些可能会导致脆弱人群中出现大量无法治疗的本地感染。
