Laboratório de Genética Molecular de Microrganismos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Hospital Federal Servidores do Estado, Ministry of Health, Rio de Janeiro, Brazil.
Sci Rep. 2023 Apr 17;13(1):6238. doi: 10.1038/s41598-023-31901-4.
Polymyxin-carbapenem-resistant Klebsiella pneumoniae (PCR-Kp) with pan (PDR)- or extensively drug-resistant phenotypes has been increasingly described worldwide. Here, we report a PCR-Kp outbreak causing untreatable infections descriptively correlated with bacterial genomes. Hospital-wide surveillance of PCR-Kp was initiated in December-2014, after the first detection of a K. pneumoniae phenotype initially classified as PDR, recovered from close spatiotemporal cases of a sentinel hospital in Rio de Janeiro. Whole-genome sequencing of clinical PCR-Kp was performed to investigate similarities and dissimilarities in phylogeny, resistance and virulence genes, plasmid structures and genetic polymorphisms. A target phenotypic profile was detected in 10% (12/117) of the tested K. pneumoniae complex bacteria recovered from patients (8.5%, 8/94) who had epidemiological links and were involved in intractable infections and death, with combined therapeutic drugs failing to meet synergy. Two resistant bacterial clades belong to the same transmission cluster (ST437) or might have different sources (ST11). The severity of infection was likely related to patients' comorbidities, lack of antimicrobial therapy and predicted bacterial genes related to high resistance, survival, and proliferation. This report contributes to the actual knowledge about the natural history of PCR-Kp infection, while reporting from a time when there were no licensed drugs in the world to treat some of these infections. More studies comparing clinical findings with bacterial genetic markers during clonal spread are needed.
泛耐药（PDR）或广泛耐药表型的多黏菌素-碳青霉烯类耐药肺炎克雷伯菌（PCR-Kp）在全球范围内已越来越多地被描述。在此，我们报告了一起 PCR-Kp 暴发事件，这些感染无法治疗，与细菌基因组存在明确的相关性。2014 年 12 月，在里约热内卢一家哨点医院发现了首例最初被归类为 PDR 的肺炎克雷伯菌表型后，开始对 PCR-Kp 进行全院范围的监测。对临床 PCR-Kp 进行全基因组测序，以调查其在系统发育、耐药和毒力基因、质粒结构和遗传多态性方面的相似性和差异性。在从具有流行病学联系且参与难治性感染和死亡的患者中分离出的 117 株肺炎克雷伯菌复合体细菌中（8.5%，8/94）检测到 10%（12/117）的目标表型谱，联合治疗药物未能达到协同作用。两个耐药菌系属于同一传播群（ST437）或可能来自不同来源（ST11）。感染的严重程度可能与患者的合并症、缺乏抗菌治疗以及与高耐药性、生存和增殖相关的预测细菌基因有关。本报告有助于了解 PCR-Kp 感染的自然史，同时也报告了在当时世界上还没有治疗这些感染的许可药物的情况下发生的情况。需要更多的研究比较临床发现与细菌遗传标记在克隆传播期间的关系。
